Publications by authors named "Frank Alexis"

63 Publications

Natural Biomaterials from Biodiversity for Healthcare Applications.

Adv Healthc Mater 2021 Oct 13:e2101389. Epub 2021 Oct 13.

School of Biological Sciences & Engineering, Yachay Tech University, Urcuquí, 100119, Ecuador.

Natural biomaterials originating during the growth cycles of all living organisms have been used for many applications. They span from bioinert to bioactive materials including bioinspired ones. As they exhibit an increasing degree of sophistication, natural biomaterials have proven suitable to address the needs of the healthcare sector. Here, we review the different natural healthcare biomaterials, their biodiversity sources, properties and promising healthacre applications. We also discuss the variability of their properties as a result of considered species and their habitat. Finally, we discuss some limitations of natural biomaterials and provide possible future developments as more natural biomaterials are yet to be discovered and studied. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/adhm.202101389DOI Listing
October 2021

Scaled Synthesis of Polyamine-Modified Cellulose Nanocrystals from Bulk Cotton and Their Use for Capturing Volatile Organic Compounds.

Polymers (Basel) 2021 Sep 10;13(18). Epub 2021 Sep 10.

Department of Chemistry, Clemson University, Clemson, SC 29634, USA.

We have previously demonstrated that cellulose nanocrystals modified with poly(ethylenimine) (PEI--CNC) are capable of capturing volatile organic compounds (VOCs) associated with malodors. In this manuscript, we describe our efforts to develop a scalable synthesis of these materials from bulk cotton. This work culminated in a reliable protocol for the synthesis of unmodified cellulose nanocrystals (CNCs) from bulk cotton on a 0.5 kg scale. Additionally, we developed a protocol for the modification of the CNCs by means of sequential 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO) oxidation and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) coupling to modify their surface with poly(ethylenimine) on a 100 g scale. Subsequently, we evaluated the performance of the PEI--CNC materials that were prepared in a series of VOC capture experiments. First, we demonstrated their efficacy in capturing volatile fatty acids emitted at a rendering plant when formulated as packed-bed filter cartridges. Secondly, we evaluated the potential to use aqueous PEI--CNC suspensions as a spray-based delivery method for VOC remediation. In both cases, the PEI--CNC formulations reduced detectable malodor VOCs by greater than 90%. The facile scaled synthesis of these materials and their excellent performance at VOC remediation suggest that they may emerge as a useful strategy for the remediation of VOCs associated with odor.
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http://dx.doi.org/10.3390/polym13183060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8470832PMC
September 2021

Bimodal Ultrasound and X-ray Bioimaging Properties of Particulate Calcium Fluoride Biomaterial.

Molecules 2021 Sep 7;26(18). Epub 2021 Sep 7.

School of Biological Sciences and Engineering, Yachay Tech University, Urcuquí 100650, Ecuador.

Ultrasound (US) and X-ray imaging are diagnostic methods that are commonly used to image internal body structures. Several organic and inorganic imaging contrast agents are commercially available. However, their synthesis and purification remain challenging, in addition to posing safety issues. Here, we report on the promise of widespread, safe, and easy-to-produce particulate calcium fluoride (-CaF) as a bimodal US and X-ray contrast agent. Pure and highly crystalline -CaF is obtained using a cheap commercial product. Scanning electron microscopy (SEM) depicts the morphology of these particles, while energy-dispersive X-ray spectroscopy (EDS) confirms their chemical composition. Diffuse reflectance ultraviolet-visible spectroscopy highlights their insulating behavior. The X-ray diffraction (XRD) pattern reveals that -CaF crystallizes in the face-centered cubic cell lattice. Further analyses regarding peak broadening are performed using the Scherrer and Williamson-Hall (W-H) methods, which pinpoint the small crystallite size and the presence of lattice strain. X-ray photoelectron spectroscopy (XPS) solely exhibits specific peaks related to CaF, confirming the absence of any contamination. Additionally, in vitro cytotoxicity and in vivo maximum tolerated dose (MTD) tests prove the biocompatibility of -CaF. Finally, the results of the US and X-ray imaging tests strongly signal that -CaF could be exploited in bimodal bioimaging applications. These findings may shed a new light on calcium fluoride and the opportunities it offers in biomedical engineering.
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http://dx.doi.org/10.3390/molecules26185447DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8472579PMC
September 2021

Distinct Methodologies to Produce Capped Mesoporous Silica with Hydroxyapatite and the Influence in Intracellular Signaling as Cytotoxicity on Human Umbilical Vein Endothelial Cells.

Bioengineering (Basel) 2021 Sep 12;8(9). Epub 2021 Sep 12.

Laboratory of Synthesis of Novel Radiopharmaceuticals and Nanoradiopharmacy, Nuclear Engineering Institute, Brazilian Nuclear Energy Commission, Rio de Janeiro 21941906, Brazil.

Mesoporous silica has unique properties such as controllable mesoporous structure and size, good biocompatibility, high specific surface area, and large pore volume. For that reason, this material has been broadly functionalized for biomedical applications, such as optical imaging, magnetic resonance imaging (MRI), positron emission tomography (PET), computed tomography (CT), ultrasound imaging, and widely employed as drug delivery systems. In this study, we synthesized fiber-type mesoporous silica capped with hydroxyapatite (ordered SiO-CaO-PO mesoporous silica). Its biological activity was evaluated through a cellular and molecular approach using HUVEC cell culture. Two distinct methodologies have produced the ordered SiO-CaO-PO mesoporous silica: (i) two-step Ca-doped silica matrix followed by hydroxyapatite crystallization inside the Ca-doped silica matrix and (ii) one-step Ca-doped silica matrix formed with the hydroxyapatite crystallization. Further analysis included: elemental analysis, transmission, scanning electron microscopy images, Small and Wide-Angle X-ray Diffraction analysis, Fourier Transform Infrared, and in vitro assays with HUVEC (cytotoxicity and immunoblotting). The hydroxyapatite capping methodology significantly affected the original mesoporous material structure. Furthermore, no cellular or molecular effect has been observed. The promising results presented here suggest that the one-step method to obtain hydroxyapatite capped mesoporous silica was effective, also demonstrating that this material has potential in biomedical applications.
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http://dx.doi.org/10.3390/bioengineering8090125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8465229PMC
September 2021

Persistent organic pollutants: The trade-off between potential risks and sustainable remediation methods.

J Environ Manage 2021 Dec 15;300:113737. Epub 2021 Sep 15.

Department of Materials, Escuela Politécnica Nacional, Ladrón de Guevara E11-253, Quito, 170525, Ecuador. Electronic address:

Persistent Organic Pollutants (POPs) have become a very serious issue for the environment because of their toxicity, resistance to conventional degradation mechanisms, and capacity to bioconcentrate, bioaccumulate and biomagnify. In this review article, the safety, regulatory, and remediation aspects of POPs including aromatic, chlorinated, pesticides, brominated, and fluorinated compounds, are discussed. Industrial and agricultural activities are identified as the main sources of these harmful chemicals, which are released to air, soil and water, impacting on social and economic development of society at a global scale. The main types of POPs are presented, illustrating their effects on wildlife and human beings, as well as the ways in which they contaminate the food chain. Some of the most promising and innovative technologies developed for the removal of POPs from water are discussed, contrasting their advantages and disadvantages with those of more conventional treatment processes. The promising methods presented in this work include bioremediation, advanced oxidation, ionizing radiation, and nanotechnology. Finally, some alternatives to define more efficient approaches to overcome the impacts that POPs cause in the hydric sources are pointed out. These alternatives include the formulation of policies, regulations and custom-made legislation for controlling the use of these pollutants.
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http://dx.doi.org/10.1016/j.jenvman.2021.113737DOI Listing
December 2021

Preliminary studies on drug delivery of polymeric primaquine microparticles using the liver high uptake effect based on size of particles to improve malaria treatment.

Mater Sci Eng C Mater Biol Appl 2021 Sep 25;128:112275. Epub 2021 Jun 25.

Brazilian Nuclear Energy Commission, Nuclear Engineering Institute, Laboratory of Novel Radiopharmaceuticals and Nano-radiopharmacy, Rio de Janeiro 21941906, Brazil; Zona Oeste State University, Laboratory of Nanoradiopharmaceuticals and Radiopharmacy, Rio de Janeiro 23070200, Brazil. Electronic address:

Malaria is the most common parasitic disease around the world, especially in tropical and sub-tropical regions. This parasitic disease can have a rapid and severe evolution. It is transmitted by female anopheline mosquitoes. There is no reliable vaccine or diagnostic test against malaria; instead, Artesunate is used for the treatment of severe malaria and Artemisinin is used for uncomplicated falciparum malaria. However, these treatments are not efficient against severe malaria and improvements are needed. Primaquine (PQ) is one of the most widely used antimalarial drugs. It is the only available drug to date for combating the relapsing form of malaria. Nevertheless, it has severe side effects. Particle drug-delivery systems present the ability to enhance the therapeutic properties of drugs and decrease their side effects. Here, we report the development of Polymeric Primaquine Microparticles (PPM) labeled with 99mTc for therapeutic strategy against malaria infection. The amount of primaquine encapsulated into the PPM was 79.54%. PPM presented a mean size of 929.47 ± 37.72 nm, with a PDI of 0.228 ± 0.05 showing a homogeneous size for the microparticles and a monodispersive behavior. Furthermore, the biodistribution test showed that primaquine microparticles have a high liver accumulation. In vivo experiments using mice show that the PPM treatments resulted in partial efficacy and protection against the development of the parasite compared to free Primaquine. These results suggest that microparticles drug delivery systems of primaquine could be a possible approach for malaria prevention and treatment.
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http://dx.doi.org/10.1016/j.msec.2021.112275DOI Listing
September 2021

Graphene quantum dots decorated with imatinib for leukemia treatment.

J Drug Deliv Sci Technol 2021 Feb 28;61. Epub 2020 Sep 28.

Brazilian Nuclear Energy Commission, Nuclear Engineering Institute, Laboratory of Nanoradiopharmaceuticals and Synthesis of Novel Radiopharmaceuticals, Rio de Janeiro, Brazil.

The use of graphene quantum dots as biomedical device and drug delivery system has been increasing. This nanoplatform of pure carbon has showed unique properties and showed to be safe for human use. The imatinib is a molecule designed to specifically inhibit the tyrosine kinase, used for leukemia treatment. In this study, we successfully decorated the graphene quantum dots ([email protected]) by a carbodiimide crosslinking reaction. The [email protected] were characterized by FTIR and AFM. The nanoparticles' in vitro behaviors were evaluated by cellular trafficking (internalization) assay and cell viability and apoptosis assays in various cancer cell lines, including suspension (leukemia) cells and adherent cancer cells. The results showed that the incorporation of the imatinib on the surface of the graphene quantum dots did not change the nanoparticles' morphology and properties. The [email protected] could be efficiently internalized and kill cancer cells via the induction of apoptosis. The data indicated that the prepared [email protected] might be a great drug nano-platform for cancer, particularly leukemia treatments.
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http://dx.doi.org/10.1016/j.jddst.2020.102117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8389840PMC
February 2021

In Situ Photopolymerization of Acrylamide Hydrogel to Coat Cellulose Acetate Nanofibers for Drug Delivery System.

Polymers (Basel) 2021 Jun 3;13(11). Epub 2021 Jun 3.

Department of Chemistry, Clemson University, Clemson, SC 29634, USA.

In this study we developed electrospun cellulose acetate nanofibers (CANFs) that were loaded with a model non-steroidal anti-inflammatory drug (NSAID) (ibuprofen, Ib) and coated with poly(acrylamide) (poly-AAm) hydrogel polymer using two consecutive steps: an electrospinning process followed by photopolymerization of AAm. Coated and non-coated CANF formulations were characterized by several microscopic and spectroscopic techniques to evaluate their physicochemical properties. An analysis of the kinetic release profile of Ib showed noticeable differences due to the presence or absence of the poly-AAm hydrogel polymer. Poly-AAm coating facilitated a constant release rate of drug as opposed to a more conventional burst release. The non-coated CANFs showed low cumulative drug release concentrations (ca. 35 and 83% at 5 and 10% loading, respectively). Conversely, poly-AAm coated CANFs were found to promote the release of drug (ca. 84 and 99.8% at 5 and 10% loading, respectively). Finally, the CANFs were found to be superbly cytocompatible.
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http://dx.doi.org/10.3390/polym13111863DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200032PMC
June 2021

Factors affecting the biological response of Graphene.

Colloids Surf B Biointerfaces 2021 Jul 14;203:111767. Epub 2021 Apr 14.

Brazilian Nuclear Energy Commission, Nuclear Engineering Institute, Laboratory of Novel Radiopharmaceuticals and Nanoradiopharmacy, R. Helio de Almeida, 75, Rio de Janeiro, 21941906, Brazil; Zona Oeste State University, Laboratory of Nanoradiopharmacy and Synthesis of Radiopharmaceuticals, Av Manuel caldeira de Alvarenga, 200, Campo Grande, Rio de Janeiro, 2100000, Brazil. Electronic address:

Nanotechnology has gained significant importance in different fields of medical, electronic, and environmental science. This technology is founded on the use of materials at the nanoscale scale (1-100 nanometers) for various purposes, particularly in the biomedical area, where its application is growing daily due to the need of materials with advanced properties. Over the past few years, there has been a growing use for graphene and its derivative composite materials. However, different physico-chemical properties influence its biological response; therefore, further studies to explain the interactions of these nanomaterials with biological systems are critical. This review presents the current advances in the applications of graphene in biomedicine with a focus on the physico-chemical characteristics of the graphene family and their influences on biological interactions.
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http://dx.doi.org/10.1016/j.colsurfb.2021.111767DOI Listing
July 2021

Dual Encapsulated Dacarbazine and Zinc Phthalocyanine Polymeric Nanoparticle for Photodynamic Therapy of Melanoma.

Pharm Res 2021 Feb 18;38(2):335-346. Epub 2021 Feb 18.

Brazilian Nuclear Energy Commission, Nuclear Engineering Institute, Rua Helio de Almeida, 75, Ilha do Fundão, Rio de Janeiro, Brazil.

Purpose: Melanoma is an invasive and very aggressive skin cancer due to its multi-drug resistance that results in poor patient survival. There is a need to test new treatment approaches to improve therapeutic efficacy and reduce side effects of conventional treatments.

Methods: PLA/PVA nanoparticles carrying both Dacarbazine and zinc phthalocyanine was produced by double emulsion technique. The characterization was performed by dynamic light scattering and atomic force microscopy. In vitro photodynamic therapy test assay using MV3 melanoma cells as a model has been performed. In vitro cell viability (MTT) was performed to measure cell toxicity of of nanoparticles with and without drugs using human endothelial cells as a model. The in vivo assay (biodistribution/tissue deposition) has been performed using radiolabeled PLA/PVA NPs.

Results: The nanoparticles produced showed a mean diameter of about 259 nm with a spherical shape. The in-vitro photodynamic therapy tests demonstrated that the combination is critical to enhance the therapeutic efficacy and it is dose dependent. The in vitro cell toxicity assay using endothelial cells demonstrated that the drug encapsulated into nanoparticles had no significant toxicity compared to control samples. In-vivo results demonstrated that the drug loading affects the biodistribution of the nanoparticle formulations (NPs). Low accumulation of the NPs into the stomach, heart, brain, and kidneys suggested that common side effects of Dacarbazine could be reduced.

Conclusion: This work reports a robust nanoparticle formulation with the objective to leveraging the synergistic effects of chemo and photodynamic therapies to potentially suppressing the drug resistance and reducing side effects associated with Dacarbazine. The data corroborates that the dual encapsulated NPs showed better in-vitro efficacy when compared with the both compounds alone. The results support the need to have a dual modality NP formulation for melanoma therapy by combining chemotherapy and photodynamic therapy.
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http://dx.doi.org/10.1007/s11095-021-02999-wDOI Listing
February 2021

Polytetrafluoroethylene-like Nanoparticles as a Promising Contrast Agent for Dual Modal Ultrasound and X-ray Bioimaging.

ACS Biomater Sci Eng 2021 03 16;7(3):1181-1191. Epub 2021 Feb 16.

School of Biological Sciences and Engineering, Yachay Tech University, 100650 Urcuquí, Ecuador.

Various noninvasive imaging techniques are used to produce deep-tissue and high-resolution images for biomedical research and clinical purposes. Organic and inorganic bioimaging agents have been developed to enhance the resolution and contrast intensity. This paper describes the synthesis of polytetrafluoroethylene-like nanoparticles (PTFE≈ NPs), their characterization, biological activity, and bioimaging properties. Transmission electron microscopy (TEM) images showed the shape and the size of the as-obtained small and ultrasmall PTFE≈ NPs. Fourier transform infrared spectroscopy (FTIR) confirmed the PTFE-like character of the samples. X-ray diffraction (XRD) enabled the determination of the crystallization system, cell lattice, and index of crystallinity of the material in addition to the presence of titania (TiO) as the contamination. These findings were corroborated by X-ray photoelectron spectroscopy (XPS) that identifies the chemical states of the elements present in the samples along with their atomic percentages allowing the determination of both the purity index of the sample and the nature of the impurities. Additionally, diffuse reflectance ultraviolet-visible spectroscopy (UV-vis) was used to further assess the optical properties of the materials. Importantly, PTFE≈ NPs showed significant and biocompatibility. Lastly, PTFE≈ NPs were tested for their ultrasound and X-ray contrast properties. Our encouraging preliminary results open new avenues for PTFE-like nanomaterials as a suitable multifunctional contrast agent for biomedical imaging applications. Combined with suitable surface chemistry and morphology design, these findings shed light to new opportunities offered by PTFE nanoparticles in the ever-booming biomedical field.
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http://dx.doi.org/10.1021/acsbiomaterials.0c01635DOI Listing
March 2021

Natural Cellulose Fibers for Surgical Suture Applications.

Polymers (Basel) 2020 Dec 18;12(12). Epub 2020 Dec 18.

School of Biological Sciences and Engineering, Yachay Tech University, Urcuquí, Imbabura 100115, Ecuador.

Suture biomaterials are critical in wound repair by providing support to the healing of different tissues including vascular surgery, hemostasis, and plastic surgery. Important properties of a suture material include physical properties, handling characteristics, and biological response for successful performance. However, bacteria can bind to sutures and become a source of infection. For this reason, there is a need for new biomaterials for suture with antifouling properties. Here we report two types of cellulose fibers from coconut () and sisal (), which were purified with a chemical method, characterized, and tested in vitro and in vivo. According to SEM images, the cellulose fiber from coconut has a porous surface, and sisal has a uniform structure without internal spaces. It was found that the cellulose fiber from sisal has mechanical properties closer to silk fiber biomaterial using Ultimate Tensile Strength. When evaluating the cellulose fibers biodegradability, the cellulose from coconut showed a rapid weight loss compared to sisal. The antifouling test was negative, which demonstrated that neither possesses intrinsic microbicidal activity. Yet, a weak biofilm was formed on sisal cellulose fibers suggesting it possesses antifouling properties compared to cellulose from coconut. In vivo experiments using healthy mice demonstrated that the scarring and mechanical connection was like silk for both cellulose fibers. Overall, our results showed the potential use of cellulose fibers from vegetal for surgical sutures due to excellent mechanical properties, rapid degradation, and no bacterial adhesion.
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http://dx.doi.org/10.3390/polym12123042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7765994PMC
December 2020

Polymer-Scaffolded Synthesis of Periodic Mesoporous Organosilica Nanomaterials for Delivery Systems in Cancer Cells.

ACS Biomater Sci Eng 2020 12 5;6(12):6671-6679. Epub 2020 Nov 5.

Department of Chemistry, Clemson University, Clemson, South Carolina 29634, United States.

We developed four types of -phenylene-bridged periodic mesoporous organosilica NPs (-P PMO NPs) with tailored physical parameters including size, morphology, porosity, and surface area using a new polymer-scaffolding approach. The particles have been formulated to facilitate the codelivery of small-molecule hydrophobic/hydrophilic cargos such as model anticancer drugs (i.e., doxorubicin hydrochloride (DOX) and -benzylguanine) and model fluorescent dyes (i.e., rhodamine 6G and Nile red). -P PMO NPs were synthesized via a cetyltrimethylammonium bromide (CTAB)-directed sol-gel process using two different organic solvents and in the presence of polymeric scaffolding constituents that led to morphologically distinct PMO NPs despite using the same organosilane precursors. After the formulation process, the polymeric scaffolding agent was conveniently washed away from the PMO NPs. Extensive analyses were used to characterize the physicochemical attributes of the PMO NPs such as their chemical composition, morphologies, etc. Spherical and rod-shaped PMOs of diameters ranging between 79 and 342 nm, surface areas between 770 and 1060 m/g, and pore volumes between 0.79 and 1.37 cm/g were prepared using the polymer-scaffolding approach. The performance of these materials toward drug-loading capacity, cytotoxicity, and cancer cell internalization was evaluated. Interestingly, the designed particles exhibited significantly high payloads of drugs and dyes (up to 78 and 94%, respectively). Cellular studies also demonstrated exceptional biocompatibility and marked internalization into both human breast cancer MCF-7 and glioblastoma U-87 MG cells. Further, DOX also possessed a noticeable release from particles and accumulation in cell nuclei with increased incubation time in vitro. Ultimately, this work validates the controlled design and synthesis of PMO NPs using a polymer-scaffolding approach and highlights the potential of these materials as excellent delivery systems for combination therapy with high loading capability to improve the therapeutic index for cancers.
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http://dx.doi.org/10.1021/acsbiomaterials.0c01082DOI Listing
December 2020

Radioactive polymeric nanoparticles for biomedical application.

Drug Deliv 2020 Dec;27(1):1544-1561

Nuclear Engineering Institute, Brazilian Nuclear Energy Commission, Rio de Janeiro, Brazil.

Nowadays, emerging radiolabeled nanosystems are revolutionizing medicine in terms of diagnostics, treatment, and theranostics. These radionuclides include polymeric nanoparticles (NPs), liposomal carriers, dendrimers, magnetic iron oxide NPs, silica NPs, carbon nanotubes, and inorganic metal-based nanoformulations. Between these nano-platforms, polymeric NPs have gained attention in the biomedical field due to their excellent properties, such as their surface to mass ratio, quantum properties, biodegradability, low toxicity, and ability to absorb and carry other molecules. In addition, NPs are capable of carrying high payloads of radionuclides which can be used for diagnostic, treatment, and theranostics depending on the radioactive material linked. The radiolabeling process of nanoparticles can be performed by direct or indirect labeling process. In both cases, the most appropriate must be selected in order to keep the targeting properties as preserved as possible. In addition, radionuclide therapy has the advantage of delivering a highly concentrated absorbed dose to the targeted tissue while sparing the surrounding healthy tissues. Said another way, radioactive polymeric NPs represent a promising prospect in the treatment and diagnostics of cardiovascular diseases such as cardiac ischemia, infectious diseases such as tuberculosis, and other type of cancer cells or tumors.
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http://dx.doi.org/10.1080/10717544.2020.1837296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7599028PMC
December 2020

Biomedical Science to Tackle the COVID-19 Pandemic: Current Status and Future Perspectives.

Molecules 2020 Oct 11;25(20). Epub 2020 Oct 11.

School of Biological Sciences and Engineering, Yachay Tech University, Urcuquí 100650, Ecuador.

The coronavirus infectious disease (COVID-19) pandemic emerged at the end of 2019, and was caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which has resulted in an unprecedented health and economic crisis worldwide. One key aspect, compared to other recent pandemics, is the level of urgency, which has started a race for finding adequate answers. Solutions for efficient prevention approaches, rapid, reliable, and high throughput diagnostics, monitoring, and safe therapies are needed. Research across the world has been directed to fight against COVID-19. Biomedical science has been presented as a possible area for combating the SARS-CoV-2 virus due to the unique challenges raised by the pandemic, as reported by epidemiologists, immunologists, and medical doctors, including COVID-19's survival, symptoms, protein surface composition, and infection mechanisms. While the current knowledge about the SARS-CoV-2 virus is still limited, various (old and new) biomedical approaches have been developed and tested. Here, we review the current status and future perspectives of biomedical science in the context of COVID-19, including nanotechnology, prevention through vaccine engineering, diagnostic, monitoring, and therapy. This review is aimed at discussing the current impact of biomedical science in healthcare for the management of COVID-19, as well as some challenges to be addressed.
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http://dx.doi.org/10.3390/molecules25204620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7587204PMC
October 2020

Radioactive gold nanocluster (198-AuNCs) showed inhibitory effects on cancer cells lines.

Artif Cells Nanomed Biotechnol 2020 Dec;48(1):1214-1221

Brazilian Nuclear Energy Commission, Nuclear Engineering Institute, Rio de Janeiro, Brazil.

Cancer is a global epidemic disease responsible for over ten millions death worldwide. The early diagnosis and the precise treatment with reduced adverse reactions are the main goal worldwide. In this study, we produced, characterized and evaluated ( in three different cancer cell lines (protaste, breast and melanoma) a radioactive gold nanocluster (R-AuNC) (Au25(Capt)18). The pharmacokinetics as the influence in the ABC transporter (MRP1 Efflux Transporter Protein) was also evaluated. The results showed that R-AuNC (Au25(Capt)18) are capable to kill the cancer cells lines of protaste, breast and melanoma. The pharmacokinetics showed a fast clearance and great volume of distribution, confirming the use of R-AuNC as nanomedicine for cancer treatment. Finally, the ABC transporter assay corroborated that the R-AuNC (Au25(Capt)18) has no risk of being pumped out of cells by this efflux transporter. The results validate the use of gold nanoparticles as therapeutic nanomedicine for cancer treatment.
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http://dx.doi.org/10.1080/21691401.2020.1821698DOI Listing
December 2020

Microcrystalline Cellulose Extracted from Native Plants as an Excipient for Solid Dosage Formulations in Drug Delivery.

Nanomaterials (Basel) 2020 May 19;10(5). Epub 2020 May 19.

School of Biological Sciences and Engineering, Yachay Tech University, Urcuquí 100650, Ecuador.

Excipients represent the complement of the active principle in any pharmaceutical form. Their function is to provide stability, protection, and to ensure absorption of the drug and acceptability in patients. Cellulose is a conventional excipient in many pharmaceutical solid dosage products. Most of the sources used to extract microcrystalline cellulose come from cotton or wood, which are expensive and in high demand from other industries. As plants are considered the main source of excipient production, we have taken advantage of the biodiversity of Ecuador to evaluate microcrystalline cellulose extracted from borojó (), a native plant, as an excipient for solid dosage formulations. The method of choice for tablet manufacturing was direct compression since it is a conventional fabrication method in the pharmaceutical industry. First, we performed scanning electron microscopy (SEM), Fourier-transform infrared (FTIR) spectroscopy, and X-ray diffraction (XRD) in order to compare the structure and characteristics of the extracted cellulose with two reference commercial cellulose materials. Second, we performed quality tests to evaluate the use of the isolate as an excipient including fluidity, hardness, friability, and disintegration. Compared with commercial and microcrystalline cellulose, the extracted cellulose from the native plant showed comparable characteristics and is consequently a potential excipient that could be used in the pharmaceutical industry. Last, we performed a dissolution test in which we concluded that all tablets have a short release time of active principle.
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http://dx.doi.org/10.3390/nano10050975DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7712051PMC
May 2020

In situ preparation of gold-polyester nanoparticles for biomedical imaging.

Biomater Sci 2020 Jun 21;8(11):3032-3043. Epub 2020 Apr 21.

Department of Chemistry, Clemson University, Clemson, SC, USA.

The synthesis and application of gold nanoparticles (AuNPs) have attracted much attention due to their interesting optical and chemical properties, as well as their utility in imaging, therapeutics, sensors, electronics, and catalysis. AuNPs are synthesized using multiple approaches, followed by chemical modification or encapsulation, to enhance their colloidal stability, biocompatibility, and targeting. Here, we report the one-step synthesis of gold-polyester nanoparticles for use as an imaging agent. The AuNPs were prepared inside polymeric NPs by means of ultraviolet irradiation of a gold salt in the presence of Irgacure I-2959 photoinitiator. We monitored the kinetic growth and nucleation of AuNPs (in vitro and ex vivo) over time using spectral analysis. Moreover, we investigated the cytotoxicity, localized plasmonic surface resonance (LSPR), and cellular imaging capabilities of the Au-polyester nanoparticles. The resulting Au-polyester NPs were characterized by Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), X-ray diffraction (XRD), dynamic light scattering (DLS), and transmission electron microscopy (TEM) to probe their chemical structure, size, zeta potential (ζ), and morphology, respectively. Furthermore, in vitro experiments showed that the NP formulation is stable over time and exhibits negligible toxicity against 3T3 fibroblast and U-87 MG glioblastoma cells. The results also demonstrated that the Au-polyester NPs exhibit excellent cellular imaging properties. This one-step strategy goes beyond current syntheses of gold-polyester nanoparticles because it can be used to synthesize the imaging agent in situ (i.e., in living cells) in lieu of conventional ex situ approaches.
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http://dx.doi.org/10.1039/d0bm00175aDOI Listing
June 2020

Iodinated Polyesters with Enhanced X-ray Contrast Properties for Biomedical Imaging.

Sci Rep 2020 01 30;10(1):1508. Epub 2020 Jan 30.

Department of Chemistry, Clemson University, 467 Hunter Laboratories, Clemson, SC, 29634, USA.

Synthetic materials exhibiting contrast imaging properties have become vital to the field of biomedical imaging. However, polymeric biomaterials are lacking imaging contrast properties for deep tissue imaging. This report details the synthesis and characterization of a suite of aryl-iodo monomers, which were used to prepare iodinated polyesters using a pre-functionalization approach. Commercially available 4-iodo-phenylalanine or 4-iodobenzyl bromide served as the starting materials for the synthesis of three iodinated monomeric moieties (a modified lactide, morpholine-2,5-dione, and caprolactone), which under a tin-mediated ring-opening polymerization (ROP), generated their respective polyesters (PE) or poly(ester amides) (PEA). An increase in X-ray intensity of all synthesized iodine-containing polymers, in comparison to non-iodinated poly(lactic acid) (PLA), validated their functionality as radio-opaque materials. The iodinated-poly(lactic acid) (iPLA) material was visualized through varying thicknesses of chicken tissue, thus demonstrating its potenial as a radio-opaque biomaterial.
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http://dx.doi.org/10.1038/s41598-020-57720-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6992777PMC
January 2020

Lycopene used as Anti-inflammatory Nanodrug for the Treatment of Rheumathoid Arthritis: Animal assay, Pharmacokinetics, ABC Transporter and Tissue Deposition.

Colloids Surf B Biointerfaces 2020 Apr 20;188:110814. Epub 2020 Jan 20.

Brazilian Nuclear Energy Commission, Nuclear Engineering Institute, Rio De Janeiro, Brazil; Zona Oeste State University, Laboratory of Radiopharmacy and Nanoradiopharmaceuticals, Rio De Janeiro, Brazil. Electronic address:

Lycopene is a carotenoid drug that has demonstrated several properties, including antioxidant and anti-inflammatory activity. The absorption in human body is very low (10-30 % only). In order to increase the bioavailability, lycopene nanoemulsion was formulated and characterized (atomic force microscopy, thermogravimetric analysis dynamic light scattering and differential scanning calorimetry). Also in vitro assay to evaluate the at-binding with MPR1 was performed. Finally, in vivo assay in animals inducted with rheumathoid arthritis were performed. The results showed that the formulated nanolycopene had superior efficacy when compared with the conventional lycopene (not nano-formulated) in inducted animals (rheumatoid arthritis). The results support the use of nanolycopene as an anti-inflammatory agent for rheumatoid arthritis therapy.
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http://dx.doi.org/10.1016/j.colsurfb.2020.110814DOI Listing
April 2020

Molecular and Cellular Risk Assessment of Healthy Human Cells and Cancer Human Cells Exposed to Nanoparticles.

Int J Mol Sci 2019 Dec 28;21(1). Epub 2019 Dec 28.

Brazilian Nuclear Energy Commission, Nuclear Engineering Institute, Rio de Janeiro 21941906, Brazil.

Nanodrugs have in recent years been a subject of great debate. In 2017 alone, almost 50 nanodrugs were approved for clinical use worldwide. Despite the advantages related to nanodrugs/nanomedicine, there is still a lack of information regarding the biological safety, as the real behavior of these nanodrugs in the body. In order to better understand these aspects, in this study, we evaluated the effect of polylactic acid (PLA) nanoparticles (NPs) and magnetic core mesoporous silica nanoparticles (MMSN, of 1000 nm and 50 nm, respectively, on human cells. In this direction we evaluated the cell cycle, cytochemistry, proliferation and tubulogenesis on tumor cells lines: from melanoma (MV3), breast cancer (MCF-7, MDA-MB-213), glioma (U373MG), prostate (PC3), gastric (AGS) and colon adenocarcinoma (HT-29) and non-tumor cell lines: from human melanocyte (NGM), fibroblast (FGH) and endothelial (HUVEC), respectively. The data showed that an acute exposure to both, polymeric nanoparticles or MMSN, did not show any relevant toxic effects on neither tumor cells nor non-tumor cells, suggesting that although nanodrugs may present unrevealed aspects, under acute exposition to human cells they are harmless.
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http://dx.doi.org/10.3390/ijms21010230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6981945PMC
December 2019

Periodic mesoporous organosilica nanomaterials for rapid capture of VOCs.

Chem Commun (Camb) 2020 Jan 12;56(4):607-610. Epub 2019 Dec 12.

Department of Chemistry, Clemson University, Clemson, SC 29634, USA.

Periodic mesoporous organosilica nanoparticles (PMO SiNPs) were developed for the targeted capture of specific volatile organic compounds (VOCs). The removal kinetics for adsorbing VOCs were fast and the maximum removal could be achieved within less than 30 min. PMO SiNPs removed >99% of VOCs at a low sorbent dose (i.e. >0.5 mL analyte per g PMO SiNPs). They also showed good recyclability and maintained reasonable removal efficiencies after five cycles (i.e. 77% and 65% for hexanal and butyric acid vapors, respectively).
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http://dx.doi.org/10.1039/c9cc09024jDOI Listing
January 2020

Nanostructured and Photochromic Material for Environmental Detection of Metal Ions.

Molecules 2019 Nov 21;24(23). Epub 2019 Nov 21.

Laboratório de Sistemas Poliméricos e Supramoleculares, Instituto de Física e Química, Universidade Federal de Itajubá, Itajubá 37500-903, Brazil.

Compared to conventional spectroscopy or chromatography analysis, chemical sensing based on colorimetric changes offers an alternative to monitor potential metal hazards in aqueous environment through rapid and low-cost colorimetric changes which can be easily interpreted In this work poly(ethylene glycol) (PEG 2000) was modified with a carboxylic acid spiropyran (SPCOOH) derivate by Steglich esterification (PEGSP2). PEGSP2 was incorporated into a poly(-caprolactone) (PCL) polymer matrix by electrospinning technique to produce nanofibers with photochromic properties. Spectroscopic analysis, thermal gravimetric analysis (TGA), and differential scanning calorimetry (DSC) were used to characterize PEGSP2. Drop shape analysis (DSA) and scanning electronic microscopy (SEM) were used to characterize the electrospun (ES) nanofibers morphology. Several metal ions solutions relevant to environmental hazards were prepared to be spotted on the surface of ES nanofibers for photochromatic sensing. Among them, Mg, Ca, Zn, Cd, La, and Er demonstrated orange fluorescence when exposed to UV light. ES nanofibers also presented higher wettability when compared to a pure PCL polymer matrix, which is critical for sensitivity. Eighteen metals ions could be detected on the electrospun material. Additionally, among all metal ions Fe was the most sensitive one in solution, in a µmol L range.
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http://dx.doi.org/10.3390/molecules24234243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6930475PMC
November 2019

Functionalized nanoparticles containing MKP-1 agonists reduce periodontal bone loss.

J Periodontol 2019 08 13;90(8):894-902. Epub 2019 Mar 13.

Department of Oral Biology, University at Buffalo, Buffalo, NY, USA.

Background: Progress over of the past several years has elucidated a role for mitogen-activated protein kinase phosphatase to regulate periodontal inflammation yielding new possibilities for treatment of periodontal diseases. These studies aimed to determine if nanoparticles (NPs) loaded with a pharmacological agent that induces mitogen-activated protein kinase phosphatase have potential clinical utility for management of periodontal inflammation and alveolar bone.

Methods: Polyethylene glycol (PEG)-polylactide (PLA) (PEG-PLA) NPs were loaded with auranofin (ARN), an antirheumatic drug, to induce mitogen-activated protein kinase phosphatase (MKP)-1 expression in vitro and in vivo. Release kinetics of ARN from NPs was performed by high performance liquid chromatography (HPLC). Fluorescent-labeled NPs were used to show uptake into macrophages by flow cytometry. Real-time quantitative polymerase chain reaction (qPCR) was used to determine dual specificity protein phosphatase (Dusp)-1 mRNA induction by Auranofin-loaded nanoparticles (ARN-NPs) and viability of ARN-NPs was determined by colorimetric in vitro assays. Functional in vitro assays were used to measure functional MKP-1 induction and preclinical models using Aggregatibacter actinomycetemcomitans lipopolysaccharide-induced alveolar bone loss and microcomputed tomography was used to determine in vivo efficacy of functionalized ARN-NPs.

Results: Data indicated that ARN-NPs had reduced cytotoxicity compared with free ARN and Dusp1 mRNA and MKP-1 activity was significantly increased by ARN-NPs in vitro. Flow cytometry indicated rapid uptake into macrophages. Finally, significant bone loss reduction was observed with ARN-NPs compared with control NPs in vivo using an lipopolysaccharide-induced rat model of periodontitis.

Conclusion: Results from these studies suggest that developing NPs functionalized with ARN have anti-inflammatory activities and may be a novel adjuvant therapeutic strategy to significantly improve periodontitis therapy and outcomes.
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http://dx.doi.org/10.1002/JPER.18-0572DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7112177PMC
August 2019

Recent Advances in Polyesters for Biomedical Imaging.

Adv Healthc Mater 2018 11 8;7(22):e1800798. Epub 2018 Oct 8.

Department of Bioengineering, Clemson University, 301 Rhodes Research Center, Clemson, SC, 29634, USA.

Several synthetic materials exhibiting contrast imaging properties have become vital to the field of biomedical imaging. Polymeric biomaterials and metals are commonly used imaging agents and can assist in the monitoring of therapy response, migration, degradation, changes in morphology, defects, and image-guided surgery. In comparison to metals, most bio and synthetic polymers lack inherent imaging properties. Polymeric biomaterials, specifically polyesters, have gained a considerable amount of attention due to their unique properties including biocompatibility, biodegradation, facile synthesis, and modification capability. Polyester implants and nanomaterials are available on the market or are in clinical trials for many applications including: dental implants, cranio-maxilofacial implants, soft tissue sutures and staples, abdominal wall repair, tendon and ligament reconstruction, fracture fixation devices, and coronary drug eluting stents. This review aims to provide a summary of the recent developments of polyesters with bioimaging contrast properties. The three main approaches to prepare bioimaging polyesters (coating, encapsulation, and functionalization) are discussed in depth. Furthermore, commonly used imaging modalities including X-ray computed tomography, magnetic resonance imaging, ultrasound, fluorescence, and radionucleotide polyester contrast agents are highlighted. In each section, examples of impactful bioimaging polyesters in the five major imaging modalities are evaluated.
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http://dx.doi.org/10.1002/adhm.201800798DOI Listing
November 2018

Poly(amine) modified kaolinite clay for VOC capture.

Chemosphere 2018 Dec 4;213:19-24. Epub 2018 Sep 4.

Department of Chemistry, Clemson University, Clemson, SC 29634, USA. Electronic address:

Polyethylenimine (PEI) functionalized kaolinite clay was successfully prepared, characterized, and assessed for the remediation of volatile organic compounds (VOCs) comprising the aldehyde, carboxylic acid, and disulfide functional group classes. A gas chromatographic vapor capture assay evaluated the capability of unmodified and modified clay material to capture representative aldehyde, carboxylic acid, and disulfide VOCs in a laboratory setting. Unmodified kaolinite (Kao) clay was moderately or poorly effective at remediating these VOCs, while the poly(amine) functionalized Kao was capable of capturing VOCs in the vapor phase with reductions up to 100%. Sample cartridge tubes were packed with PEI-functionalized clay in order to assess their ability to reduce the detectable volatile fatty acid load at an open-air rendering plant in a relevant field test for applying these materials in a packed-bed scrubber application. The PEI-Kao packed cartridges were capable of significantly reducing the detectable concentration of volatile fatty acid effluent from the rendering operation. These volatile fatty acids are major contributors to nuisance odors associated with rendering.
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http://dx.doi.org/10.1016/j.chemosphere.2018.08.156DOI Listing
December 2018

Nanotechnology for Environmental Remediation: Materials and Applications.

Molecules 2018 Jul 18;23(7). Epub 2018 Jul 18.

Department of Bioengineering, Clemson University, 301 Rhodes Research Center, Clemson, SC 29634, USA.

Environmental remediation relies mainly on using various technologies (e.g., adsorption, absorption, chemical reactions, photocatalysis, and filtration) for the removal of contaminants from different environmental media (e.g., soil, water, and air). The enhanced properties and effectiveness of nanotechnology-based materials makes them particularly suitable for such processes given that they have a high surface area-to-volume ratio, which often results in higher reactivity. This review provides an overview of three main categories of nanomaterials (inorganic, carbon-based, and polymeric-based materials) used for environmental remediation. The use of these nanomaterials for the remediation of different environmental contaminants-such as heavy metals, dyes, chlorinated organic compounds, organophosphorus compounds, volatile organic compounds, and halogenated herbicides-is reviewed. Various recent examples are extensively highlighted focusing on the materials and their applications.
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http://dx.doi.org/10.3390/molecules23071760DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6100491PMC
July 2018

Longitudinal Stretching for Maturation of Vascular Tissues Using Magnetic Forces.

Bioengineering (Basel) 2016 Nov 16;3(4). Epub 2016 Nov 16.

Department of Bioengineering, Clemson University, 301 Rhodes Research Center, Clemson, SC 29634, USA.

Cellular spheroids were studied to determine their use as "bioinks" in the biofabrication of tissue engineered constructs. Specifically, magnetic forces were used to mediate the cyclic longitudinal stretching of tissues composed of Janus magnetic cellular spheroids (JMCSs), as part of a post-processing method for enhancing the deposition and mechanical properties of an extracellular matrix (ECM). The purpose was to accelerate the conventional tissue maturation process via novel post-processing techniques that accelerate the functional, structural, and mechanical mimicking of native tissues. The results of a forty-day study of JMCSs indicated an expression of collagen I, collagen IV, elastin, and fibronectin, which are important vascular ECM proteins. Most notably, the subsequent exposure of fused tissue sheets composed of JMCSs to magnetic forces did not hinder the production of these key proteins. Quantitative results demonstrate that cyclic longitudinal stretching of the tissue sheets mediated by these magnetic forces increased the Young's modulus and induced collagen fiber alignment over a seven day period, when compared to statically conditioned controls. Specifically, the elastin and collagen content of these dynamically-conditioned sheets were 35- and three-fold greater, respectively, at seven days compared to the statically-conditioned controls at three days. These findings indicate the potential of using magnetic forces in tissue maturation, specifically through the cyclic longitudinal stretching of tissues.
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http://dx.doi.org/10.3390/bioengineering3040029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5597272PMC
November 2016

Iron Oxide Nanoparticles Stimulates Extra-Cellular Matrix Production in Cellular Spheroids.

Bioengineering (Basel) 2017 Jan 21;4(1). Epub 2017 Jan 21.

Department of Bioengineering, Clemson University, 301 Rhodes Research Center, Clemson, SC 29634, USA.

Nanotechnologies have been integrated into drug delivery, and non-invasive imaging applications, into nanostructured scaffolds for the manipulation of cells. The objective of this work was to determine how the physico-chemical properties of magnetic nanoparticles (MNPs) and their spatial distribution into cellular spheroids stimulated cells to produce an extracellular matrix (ECM). The MNP concentration (0.03 mg/mL, 0.1 mg/mL and 0.3 mg/mL), type (magnetoferritin), shape (nanorod-85 nm × 425 nm) and incorporation method were studied to determine each of their effects on the specific stimulation of four ECM proteins (collagen I, collagen IV, elastin and fibronectin) in primary rat aortic smooth muscle cell. Results demonstrated that as MNP concentration increased there was up to a 6.32-fold increase in collagen production over no MNP samples. Semi-quantitative Immunohistochemistry (IHC) results demonstrated that MNP type had the greatest influence on elastin production with a 56.28% positive area stain compared to controls and MNP shape favored elastin stimulation with a 50.19% positive area stain. Finally, there are no adverse effects of MNPs on cellular contractile ability. This study provides insight on the stimulation of ECM production in cells and tissues, which is important because it plays a critical role in regulating cellular functions.
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http://dx.doi.org/10.3390/bioengineering4010004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5590449PMC
January 2017

Bright X-ray and up-conversion nanophosphors annealed using encapsulated sintering agents for bioimaging applications.

J Mater Chem B 2017 13;5(27):5412-5424. Epub 2017 Jun 13.

Department of Chemistry, Department of BioEngineering, Center for Optical Materials Science and Engineering Technologies (COMSET), and Institute of Environmental Toxicology (CU-ENTOX); Clemson University, Clemson, SC, 29634, USA. Tel:+1-864-656-1726.

Nanophosphors are promising contrast agents for deep tissue optical imaging applications because they can be excited by X-ray and near infrared light that penetrates deeply through tissue and generates almost no autofluorescence background in the tissue. For these bioimaging applications, the nanophosophors should ideally be small, monodispersed and brightly luminescent. However, most methods used to improve luminescence yield by annealing the particles to reduce crystal and surface defects (e.g. using flux or sintering agents) also cause particle fusion or require multiple component core-shell structures. Here, we report a novel method to prepare bright, uniformly sized X-ray nanophosphors (GdOS:Eu or Tb) and upconversion nanophosphors (YOS: Yb/Er, or Yb/Tm) with large crystal domain size without causing aggregation. A core-shell nanoparticle is formed, with NaF only in the core. We observe that increasing the NaF sintering agent concentration up to 7.6 mol% increases both crystal domain size and luminescence intensity (up to 40% of commercial microphosphors) without affecting the physical particticle diameter. Above 7.6 mol%, particle fusion is observed. The annealing is insensitive to the cation (Na or K) but varies strongly with anion, with F>Cl>CO>Br>I. The luminescence depends strongly on crystal domain size. The data agree reasonably well with a simple domain surface quenching model, although the size-dependence suggests additional quenching mechanisms within small domains. The prepared bright nanophosphors were subsequently functionalized with PEG-folic acid to target MCF-7 breast cancer cells which overexpress folic acid receptors. Both X-ray and upconversion nanophosphors provided low background and bright luminescence which was imaged through 1 cm chicken breast tissue at a low dose of nanophosphors 200 µL (0.1 mg/mL). We anticipate these highly monodispersed and bright X-ray and upconversion nanophosphors will have significant potential for tumor targeted imaging.
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http://dx.doi.org/10.1039/C7TB01289FDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5826634PMC
June 2017
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