Publications by authors named "Maixian Liu"

24 Publications

  • Page 1 of 1

Nephrotoxicity Evaluation of Indium Phosphide Quantum Dots with Different Surface Modifications in BALB/c Mice.

Int J Mol Sci 2020 Sep 27;21(19). Epub 2020 Sep 27.

Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen 518055, China.

InP QDs have shown a great potential as cadmium-free QDs alternatives in biomedical applications. It is essential to understand the biological fate and toxicity of InP QDs. In this study, we investigated the in vivo renal toxicity of InP/ZnS QDs terminated with different functional groups-hydroxyl (hQDs), amino (aQDs) and carboxyl (cQDs). After a single intravenous injection into BALB/c mice, blood biochemistry, QDs distribution, histopathology, inflammatory response, oxidative stress and apoptosis genes were evaluated at different predetermined times. The results showed fluorescent signals from QDs could be detected in kidneys during the observation period. No obvious changes were observed in histopathological detection or biochemistry parameters. Inflammatory response and oxidative stress were found in the renal tissues of mice exposed to the three kinds of QDs. A significant increase of KIM-1 expression was observed in hQDs and aQDs groups, suggesting hQDs and aQDs could cause renal involvement. Apoptosis-related genes (Bax, Caspase 3, 7 and 9) were up-regulated in hQDs and aQDs groups. The above results suggested InP/ZnS QDs with different surface chemical properties would cause different biological behaviors and molecular actions in vivo. The surface chemical properties of QDs should be fully considered in the design of InP/ZnS QDs for biomedical applications.
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http://dx.doi.org/10.3390/ijms21197137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7582660PMC
September 2020

Galvanic replacement synthesis of multi-branched gold nanocrystals for photothermal cancer therapy.

J Mater Chem B 2020 07;8(25):5491-5499

Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo, New York 14260, USA. and Institute for Lasers, Photonics, and Biophotonics, University at Buffalo, The State University of New York, Buffalo, New York 14260, USA and RENEW Institute, University at Buffalo, The State University of New York, Buffalo, New York 14260, USA.

We present a facile organic phase synthesis method for producing multi-branched gold nanocrystals (nanostars) with a broad localized surface plasmon resonance (LSPR) across near-infrared (NIR) to short-wave infrared (SWIR) wavelengths. In this approach, galvanic replacement of copper by gold, in seed particles produced in situ, initiates growth of multi-branched structures. The method enables broad tuning of the LSPR energy by manipulating the branch length, with peak LSPR absorbance tuned from 850 to 1880 nm, reaching SWIR wavelengths covering the second and third optical transparency windows in biological media, rarely achieved with noble metal plasmonic nanostructures. After a ligand-exchange process, the gold nanostars readily disperse in water while retaining their LSPR absorbance. The multi-branched Au nanocrystals (NCs) exhibit exceptionally high photothermal transduction efficiency, exceeding that of Au nanorods and nanoparticles, to which we make direct comparisons here. At the same time, their synthesis is much more straightforward than hollow structures like nanocages, nanoshells, and nanomatryoshkas that can also exhibit high photothermal efficiency at NIR wavelengths. In vitro photothermal heating of multi-branched Au NCs in the presence of human cervical cancer cells causes effective cell ablation after 10 min laser irradiation. Cell viability assays demonstrate that the NCs are biocompatible at doses required for photothermal therapy. These results suggest that the multi-branched Au NCs can serve as a new type of photothermal therapy agent and in other applications in which strong NIR to SWIR absorbers are needed.
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http://dx.doi.org/10.1039/d0tb00748jDOI Listing
July 2020

Synthetic and immunological studies on the OCT4 immunodominant motif antigen-based anti-cancer vaccine.

Cancer Biol Med 2020 02;17(1):132-141

Department of Physiology, School of Basic Medical Sciences, Shenzhen University Health Sciences Center, Shenzhen University, Shenzhen 518060, China.

Cancer stem cell is one of the important causes of tumorigenesis as well as a drug target in the treatment of malignant tumor. However, at present, there is no immune vaccine targeting these cells. Octamer-binding transcription factor 4 (OCT4), a marker of embryonic stem cells and germ cells, often highly expresses in the early stages of tumorigenesis and is therefore a good candidate for cancer vaccine development. To identify the optimal carrier and adjuvant combination, we chemically synthesized and linked three different OCT4 epitope antigens to a carrier protein, keyhole limpet hemocyanin (KLH), combined with Toll-like receptor 9 agonist (TLR9). Immunization with OCT4-3 + TLR9 produced the strongest immune response in mice. In prevention assays, significant tumor growth inhibition was achieved in BABL/c mice treated with OCT4-3 + TLR9 ( < 0.01). Importantly, the results showed that cytotoxic T lymphocyte activity and the inhibition of tumor growth were enhanced in mice immunized with OCT4-3 combined with TLR9. Meanwhile, multiple cytokines [such as interferon (IFN)-γ ( < 0.05), interleukin (IL)-12 ( < 0.05), IL-2 ( < 0.01), and IL-6 ( < 0.05)] promoting cellular immune responses were shown to be greatly enhanced in mice immunized with OCT4-3 + TLR9. Moreover, we considered safety considerations in terms of the composition of the vaccines to help facilitate the development of effective next-generation vaccines. Collectively, these experiments demonstrated that combination therapy with TLR9 agonist induced a tumor-specific adaptive immune response, leading to the suppression of primary tumor growth in testis embryonic carcinoma.
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http://dx.doi.org/10.20892/j.issn.2095-3941.2019.0224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7142840PMC
February 2020

Carrier-Free CXCR4-Targeted Nanoplexes Designed for Polarizing Macrophages to Suppress Tumor Growth.

Cell Mol Bioeng 2019 Oct 27;12(5):375-388. Epub 2019 Aug 27.

Department of Pharmaceutical Sciences, School of Pharmacy, University at Buffalo, The State University of New York, Buffalo, NY 14214 USA.

Introduction: Treatment options for cancer metastases, the primary cause of cancer mortality, are limited. The chemokine receptor CXCR4 is an attractive therapeutic target in cancer because it mediates metastasis by inducing cancer cell and macrophage migration. Here we engineered carrier-free CXCR4-targeting RNA-protein nanoplexes that not only inhibited cellular migration but also polarized macrophages to the M1 phenotype.

Materials And Methods: A CXCR4-targeting single-chain variable fragment (scFv) antibody was fused to a 3030 Da RNA-binding protamine peptide (RSQSRSRYYRQRQRSRRRRRRS). Self-assembling nanoplexes were formed by mixing the CXCR4-scFv-protamine fusion protein (CXCR4-scFv-RBM) with miR-127-5p, a miRNA shown to mediate M1 macrophage polarization. RNA-protein nanoplexes were characterized with regard to their physicochemical properties and therapeutic efficacy.

Results: CXCR4-targeting RNA-protein nanoplexes simultaneously acted as a targeting ligand, a macrophage polarizing drug, and a miRNA delivery vehicle. Our carrier-free, RNA-protein nanoplexes specifically bound to CXCR4-positive macrophages and breast cancer cells, showed high drug loading (~ 90% w/w), and are non-toxic. Further, these RNA-protein nanoplexes significantly inhibited cancer and immune cell migration (75 to 99%), robustly polarized macrophages to the tumor-suppressive M1 phenotype, and inhibited tumor growth in a mouse model of triple-negative breast cancer.

Conclusions: We engineered a novel class of non-toxic RNA-protein nanoplexes that modulate the tumor stroma. These nanoplexes are promising candidates for add-ons to clinically approved chemotherapeutics.
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http://dx.doi.org/10.1007/s12195-019-00589-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6816770PMC
October 2019

The Codelivery of siRNA and QDs by pH-Responsive Micelle for Hepatoma Cancer Cells.

Front Pharmacol 2019 10;10:1194. Epub 2019 Oct 10.

Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen, China.

Recently, RNA interfering (RNAi) has become a promising approach for cancer therapy. However, the application of RNAi for clinics is still hindered due to the lack of safe and efficient carriers. In this study, a pH-responsive micelle based on polycaprolactone-block-poly 2-(dimethylamino)ethyl methacrylate (PCL-PDEM) cationic copolymer was developed to carry short interfering RNA (siRNA) for silencing interleukin 8 (IL-8) gene in hepatoma cancer cells. The transfection efficiency of the PCL-PDEM-siRNA/quantum dots (QDs) nanoplex has reached about 70%, and the expression level of IL-8 decreased about 63%. Furthermore, the codelivery of QDs and siRNA has been realized, which is beneficial to visualize the process of siRNA delivery. No considerable cytotoxicity from the nanoparticles has been observed, indicating that our responsive cationic micelle is potential in clinical trial for hepatoma cancer therapy.
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http://dx.doi.org/10.3389/fphar.2019.01194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6797843PMC
October 2019

Recent advances in copper sulphide-based nanoheterostructures.

Chem Soc Rev 2019 Oct 17;48(19):4950-4965. Epub 2019 Sep 17.

School of Electrical and Electronic Engineering, College of Engineering, Nanyang Technological University, Singapore.

Due to the high mobility of copper ions in numerous structurally-related phases, copper sulphide (CuS, 0 ≤x≤ 1) has been widely used as a starting template to fabricate various heterostructures via cation exchange. Such nanoheterostructures can possess unique combinations of physical properties that could be useful in diverse applications. Controllable methods of fabricating copper sulphide nanoheterostructures of increasing complexity have been rapidly emerging over the past few years. In this tutorial review, we discuss recent progress in heterostructure fabrication methods using copper sulphide. We primarily focus on important reports of cation exchange-based approaches and then summarize some key emerging applications that can employ these copper-sulphide-based nanoheterostructures.
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http://dx.doi.org/10.1039/c8cs00832aDOI Listing
October 2019

The Ultrasmall Biocompatible CuS@BSA Nanoparticle and Its Photothermal Effects.

Front Pharmacol 2019 26;10:141. Epub 2019 Feb 26.

National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, Department of Biomedical Engineering, School of Medicine, Shenzhen University, Shenzhen, China.

Nanomaterials with localized surface plasmon resonance (LSPR) have exquisite optical properties, which allow a wide range of applications. Non-stoichiometric copper sulfides with active LSPR have drawn great attention, because its LSPR peak falls in the NIR region that is suitable for deep bioimaging and photothermal therapy (PTT). Despite numerous biomedical applications, the biocompatibility and toxicity of copper sulfides have not been studied systematically. In this contribution, we synthesized the ultrasmall biocompatible copper sulfide nanoparticle encapsulated within bovine serum albumin (BSA), CuS@BSA. The physical features of CuS@BSA were characterized. The MTT and flow cytometry assays were performed. The PTT was also investigated. The results indicated that such CuS@BSA nanoparticle had an average TEM size of 8 nm, and an average DLS size of 15 nm. A lower concentration of CuS@BSA was not toxic to HeLa cells, but the critical apoptotic events occurred in HeLa cells after co-incubation with 45 μg/mL CuS@BSA for 48 h. The photothermal effect of the CuS@BSA in aqueous medium were concentration-dependent and time-dependent, which were also verified by flow cytometry and microscopy, while the CuS@BSA were co-cultured with HeLa cells and treated with laser. This work designed an ultrasmall potential biocompatible nanoparticle, CuS@BSA, for cancer photothermal therapy, and provided the toxic information to safely guide its biomedical applications.
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http://dx.doi.org/10.3389/fphar.2019.00141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6399117PMC
February 2019

A general and rapid room-temperature synthesis approach for metal sulphide nanocrystals with tunable properties.

Nanoscale 2018 Dec;11(1):136-144

Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo, New York 14260, USA.

Colloidal metal sulphide (MS) nanocrystals (NCs) have recently attracted considerable attention because of their tunable properties that can be exploited in various physical, chemical and biological applications. In this work, we present a novel and general method for synthesis of monodispersed binary (CuS, Ag2S, CdS, PbS, and SnS), ternary (Ag-In-S, Cu-In-S and Cu-Sn-S) and quaternary (Cu-Zn-Sn-S) MS NCs. The synthesis is conducted at room temperature, with an immediate crystallization process and up to 60 seconds of growth time, enabling rapid synthesis without external heating. For some of the ternary and quaternary NCs produced with relatively low crystallinity, we then carried out a "colloidal annealing" process to improve their crystallinity without changing their composition. Moreover, we show that the morphology and optical properties of the NCs can be tuned by varying the concentration of precursors and reaction time. The shape evolution and photoluminescence of particular MS NCs were also studied. These results not only provide insights into the growth mechanisms of MS NCs, but also yield a generalized, low cost, and potentially scalable method to fabricate them.
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http://dx.doi.org/10.1039/c8nr07483fDOI Listing
December 2018

Selective Cation Incorporation into Copper Sulfide Based Nanoheterostructures.

ACS Nano 2018 Aug 17;12(8):7803-7811. Epub 2018 Jul 17.

Heterogeneous copper sulfide based nanostructures have attracted intense attention based on their potential to combine the plasmonic properties of copper-deficient copper sulfides with properties of other semiconductors and metals. In general, copper sulfides are versatile platforms for production of other materials by cation incorporation and exchange processes. However, the outcomes of subsequent cation exchange (CE) or incorporation processes involving nanoheterostructure (NH) templates have not been explored. In this work, we incorporate indium and tin into CuS-ZnS NHs. We demonstrate that the outcomes of cation incorporation are strongly influenced by heterocation identity and valence and by the presence of a Cu-extracting agent. The selectivity of cation incorporation depends upon both the cation itself and the heterodomains in which CE reactions take place. The final nanocrystals (NCs) emerge in many forms including homogeneous NCs, heterodimers, core@shell NHs and NHs with three different domains. This selective cation incorporation not only facilitates the preparation of previously unavailable metal sulfide NHs but also provides insight into mechanisms of CE reactions.
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http://dx.doi.org/10.1021/acsnano.8b01871DOI Listing
August 2018

Black phosphorus nanosheets for rapid microRNA detection.

Nanoscale 2018 Mar;10(11):5060-5064

Key Laboratory of Optoelectronics Devices and Systems of Ministry of Education/Guangdong Province, College of Optoelectronic Engineering, Shenzhen University, Shenzhen 518060, China.

Herein, for the first time, a sensitive sensing platform for rapid detection of microRNA was developed by employing black phosphorus nanosheets as the fluorescence quenching material. The biosensor displayed a good linear response to microRNA ranging from 10 nM to 1000 nM. Moreover, the biosensor could distinguish triple nucleotide polymorphism.
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http://dx.doi.org/10.1039/c7nr08900gDOI Listing
March 2018

Precision engineering of targeted nanocarriers.

Wiley Interdiscip Rev Nanomed Nanobiotechnol 2018 Feb 13. Epub 2018 Feb 13.

Department of Pharmaceutical Sciences, School of Pharmacy, University at Buffalo, The State University of New York, Buffalo, New York.

Since their introduction in 1980, the number of advanced targeted nanocarrier systems has grown considerably. Nanocarriers capable of targeting single receptors, multiple receptors, or multiple epitopes have all been used to enhance delivery efficiency and selectivity. Despite tremendous progress, preclinical studies and clinically translatable nanotechnology remain disconnected. The disconnect in targeting efficacy may stem from poorly-understood factors such as receptor clustering, spatial control of targeting ligands, ligand mobility, and ligand architecture. Further, the relationship between receptor distribution and ligand architecture remains elusive. Traditionally, targeted nanocarriers were engineered assuming a "static" target. However, it is becoming increasingly clear that receptor expression patterns change in response to external stimuli and disease progression. Here, we discuss how cutting-edge technologies will enable a better characterization of the spatiotemporal distribution of membrane receptors and their clustering. We further describe how this will enable the design of new nanocarriers that selectively target the site of disease. Ultimately, we explore how the precision engineering of targeted nanocarriers that adapt to receptor dynamics will have the potential to drive nanotechnology to the forefront of therapy and make targeted nanomedicine a clinical reality. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Biology-Inspired Nanomaterials > Lipid-Based Structures Biology-Inspired Nanomaterials > Protein and Virus-Based Structures.
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http://dx.doi.org/10.1002/wnan.1511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6089677PMC
February 2018

The microRNA regulatory landscape of MSC-derived exosomes: a systems view.

Sci Rep 2018 01 23;8(1):1419. Epub 2018 Jan 23.

Department of Pharmaceutical Sciences, School of Pharmacy, University at Buffalo, The State University of New York, Buffalo, NY, 14214, USA.

Mesenchymal stem cell (MSC)-derived exosomes mediate tissue regeneration in a variety of diseases including ischemic heart injury, liver fibrosis, and cerebrovascular disease. Despite an increasing number of studies reporting the therapeutic effects of MSC exosomes, the underlying molecular mechanisms and their miRNA complement are poorly characterized. Here we microRNA (miRNA)-profiled MSC exosomes and conducted a network analysis to identify the dominant biological processes and pathways modulated by exosomal miRNAs. At a system level, miRNA-targeted genes were enriched for (cardio)vascular and angiogenesis processes in line with observed cardiovascular regenerative effects. Targeted pathways were related to Wnt signaling, pro-fibrotic signaling via TGF-β and PDGF, proliferation, and apoptosis. When tested, MSC exosomes reduced collagen production by cardiac fibroblasts, protected cardiomyocytes from apoptosis, and increased angiogenesis in HUVECs. The intrinsic beneficial effects were further improved by virus-free enrichment of MSC exosomes with network-informed regenerative miRNAs capable of promoting angiogenesis and cardiomyocyte proliferation. The data presented here help define the miRNA landscape of MSC exosomes, establish their biological functions through network analyses at a system level, and provide a platform for modulating the overall phenotypic effects of exosomes.
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http://dx.doi.org/10.1038/s41598-018-19581-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5780426PMC
January 2018

Shape Evolution of Biconcave Djurleite CuS Nanoplatelets Produced from CuInS Nanoplatelets by Cation Exchange.

J Am Chem Soc 2017 12 14;139(51):18598-18606. Epub 2017 Dec 14.

Department of Chemical and Biological Engineering and ‡Department of Pharmaceutical Science, University at Buffalo, The State University of New York , Buffalo, New York 14260, United States.

Development of nanomaterials of previously unavailable shapes and compositions continues to be a key need and interest in nanotechnology. Here, we report the preparation of unique biconcave djurleite CuS nanoplatelets (NPls) from template CuInS (copper indium sulfide, CIS) NPls via a cation exchange (CE) reaction. Upon initiation of the CE reaction, the In ions diffuse out of the CIS crystal lattice, and the remaining copper sulfide adopts the djurleite phase almost instantly. This rapid phase transition produces numerous vacancies and defects before Cu ions can diffuse into the nanostructures. The formation of a biconcave shape is attributed to the assembly and migration of these defects. The flat surfaces of the NPls are ultimately restored through a ripening process that produces single-crystalline NPls much thicker than the starting templates. Striped NPls were observed in the final products, due to stacking faults at the boundary between newly deposited and residual layers of djurleite. These studies not only provide a better understanding of the relationships among composition, morphology, and crystal structure for copper sulfide-based nanocrystals, but also provide a pathway to a previously inaccessible morphology.
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http://dx.doi.org/10.1021/jacs.7b09577DOI Listing
December 2017

TiO -coated fluoride nanoparticles for dental multimodal optical imaging.

J Biophotonics 2018 04 18;11(4):e201700029. Epub 2017 Dec 18.

The Institute for Lasers, Photonics and Biophotonics, University at Buffalo, Buffalo, New York.

Core-shell nanostructures associated with photonics techniques have found innumerous applications in diagnostics and therapy. In this work, we introduce a novel core-shell nanostructure design that serves as a multimodal optical imaging contrast agent for dental adhesion evaluation. This nanostructure consists of a rare-earth-doped (NaYF :Yb 60%, Tm 0.5%)/NaYF particle as the core (hexagonal prism, ~51 nm base side length) and the highly refractive TiO material as the shell (~thickness of 15 nm). We show that the TiO shell provides enhanced contrast for optical coherence tomography (OCT), while the rare-earth-doped core upconverts excitation light from 975 nm to an emission peaked at 800 nm for photoluminescence imaging. The OCT and the photoluminescence wide-field images of human tooth were demonstrated with this nanoparticle core-shell contrast agent. In addition, the described core-shell nanoparticles (CSNps) were dispersed in the primer of a commercially available dental bonding system, allowing clear identification of dental adhesive layers with OCT. We evaluated that the presence of the CSNp in the adhesive induced an enhancement of 67% scattering coefficient to significantly increase the OCT contrast. Moreover, our results highlight that the upconversion photoluminescence in the near-infrared spectrum region is suitable for image of deep dental tissue.
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http://dx.doi.org/10.1002/jbio.201700029DOI Listing
April 2018

Au-CuSe heterogeneous nanocrystals for efficient photothermal heating for cancer therapy.

J Mater Chem B 2017 Jul 2;5(25):4934-4942. Epub 2017 Jun 2.

Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo, New York 14260-4200, USA.

In this study, we show that Au-CuSe heterogeneous nanocrystals have great promise for use in photothermal therapy (PTT). Ligand-stabilized heterogeneous gold-copper selenide (Au-CuSe) hybrid nanocrystals were synthesized by a colloidal gold seed-mediated method. The nanocrystals exhibit broad localized surface plasmon resonance (LSPR) across visible and near-infrared (NIR) wavelengths, arising from interactions between the two nanocrystal domains. After a ligand-exchange process, the NCs readily disperse in water while retaining their LSPR absorbance. Upon illumination with a 980 nm laser, the Au-CuSe nanocrystals produced significant photothermal heating with a photothermal transduction efficiency comparable to that of larger gold nanostructures that have been widely studied for PTT. In vitro photothermal heating of Au-CuSe nanocrystals in the presence of human cervical cancer cells caused cell ablation after 10 min laser irradiation. Cell viability assays demonstrated that the hybrid nanocrystals are biocompatible at doses needed for photothermal therapy. Overall, these heterogeneous nanocrystals provide the NIR PTT efficacy of larger gold nanorods in a much smaller overall nanostructure that may have advantages with respect to biodistribution and clearance.
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http://dx.doi.org/10.1039/c7tb01004dDOI Listing
July 2017

Galectin-1 Reduces Neuroinflammation via Modulation of Nitric Oxide-Arginase Signaling in HIV-1 Transfected Microglia: a Gold Nanoparticle-Galectin-1 "Nanoplex" a Possible Neurotherapeutic?

J Neuroimmune Pharmacol 2017 03 27;12(1):133-151. Epub 2016 Dec 27.

Department of Medicine, Division of Allergy, Immunology & Rheumatology, 6074 UB's Clinical and Translational Research Center, State University of New York at Buffalo, 875 Ellicott St, Buffalo, NY, 14203, USA.

Galectins are a family of β-galactoside-binding lectins that are important modulators of homeostasis in the central nervous system (CNS). Galectin-1 is a pivotal regulator of microglia activation that alters the immune balance from neurodegeneration to neuroprotection and could have therapeutic relevance in HIV associated neurocognitive disorders (HAND). We have previously shown that galectin-1 treatment decreased oxidative stress in microglia and hypothesize that the mechanism underlying this phenomenon is the cross regulatory interactions between Nitric oxide (NO) and Arginase I activity in microglia. We induced microglial activation and examined the effect of galectin-1 on the expression of various M1/M2 microglial phenotypic markers. Since, TNF-α is associated with activation of microglial cells involved in pathogenesis of neurodegenerative diseases, we treated HIV transfected human microglial cell cultures (CHME-5/HIV) with TNF-α followed by treatment with galectin-1, to examine the galectin-1 mediated neuro-modulatory response. Our results show that treatment of CHME-5/HIV microglia with galectin-1 reduced TNF-α induced oxidative stress by ~40%, and also significantly reduced iNOS gene expression and NO production while correspondingly increasing arginase-1, cationic amino acid transporter (CAT-1) gene expression and arginase activity. Galectin-1 treatment results in shifting microglia polarization from M1 toward the beneficial M2 phenotype which may prevent neurodegeneration and promote neuroprotection. Thus, our data suggests that galectin-1 treatment reduces neuroinflammation in the CNS microenvironment via the modulation of the NO-arginase network in microglia and thus could play a neuroprotective role in HAND. Further, the therapeutic potential of galectin-1 could be enhanced by conjugation of galectin-1 onto gold nanoparticles (Au-NP), resulting in a nanogold-galectin-1 (Au-Gal-1) multivalent complex that will have more clinical translational efficacy than free galectin-1 by virtue of increasing the payload influx.
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http://dx.doi.org/10.1007/s11481-016-9723-4DOI Listing
March 2017

Utilizing clathrin triskelions as carriers for spatially controlled multi-protein display.

Biomaterials 2016 11 28;108:120-8. Epub 2016 Aug 28.

Department of Pharmaceutical Sciences, School of Pharmacy, University at Buffalo, The State University of New York, Buffalo, NY, 14214, USA. Electronic address:

The simultaneous and spatially controlled display of different proteins on nanocarriers is a desirable property not often achieved in practice. Here, we report the use of clathrin triskelions as a versatile platform for functional protein display. We hypothesized that site-specific molecular epitope recognition would allow for effective and ordered protein attachment to clathrin triskelions. Clathrin binding peptides (CBPs) were genetically fused to mCherry and green fluorescent protein (GFP), expressed, and loaded onto clathrin triskelions by site-specific binding. Attachment was confirmed by surface plasmon resonance. mCherry fusion proteins modified with various CBPs displayed binding affinities between 470 nM and 287 μM for the clathrin triskelions. Simultaneous attachment of GFP-Wbox and mCherry-Cbox fusion constructs to the clathrin terminal domain was verified by Förster resonance energy transfer. The circulating half-lives, area under the curve, and the terminal half-lives of GFP and mCherry were significantly increased when attached to clathrin triskelions. Clathrin triskelion technology is useful for the development of versatile and multifunctional carriers for spatially controlled protein or peptide display with tremendous potential in nanotechnology, drug delivery, vaccine development, and targeted therapeutic applications.
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http://dx.doi.org/10.1016/j.biomaterials.2016.08.044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5131575PMC
November 2016

Biodegradable charged polyester-based vectors (BCPVs) as an efficient non-viral transfection nanoagent for gene knockdown of the BCR-ABL hybrid oncogene in a human chronic myeloid leukemia cell line.

Nanoscale 2016 Apr;8(17):9405-16

School of Electrical and Electronic Engineering, Nanyang Technological University, 50 Nanyang Avenue, 639798, Singapore.

First-line therapy of chronic myelogenous leukemia (CML) has always involved the use of BCR-ABL tyrosine-kinase inhibitors which is associated with an abnormal chromosome called Philadelphia chromosome. Although the overall survival rate has been improved by the current therapeutic regime, the presence of resistance has resulted in limited efficacy. In this study, an RNA interference (RNAi)-based therapeutic regime is proposed with the aim to knockdown the BCR-ABL hybrid oncogene using small interfering RNA (siRNA). The siRNA transfection rates have usually been limited due to the declining contact probability among polyplexes and the non-adherent nature of leukemic cells. Our work aims at addressing this limitation by using a biodegradable charged polyester-based vector (BCPV) as a nanocarrier for the delivery of BCR-ABL-specific siRNA to the suspension culture of a K562 CML cell line. BCR-ABL siRNAs were encapsulated in the BCPVs by electrostatic force. Cell internalization was facilitated by the BCPV and assessed by confocal microscopy and flow cytometry. The regulation of the BCR-ABL level in K562 cells as a result of RNAi was analyzed by real-time polymerase chain reaction (RT-PCR). We observed that BCPV was able to form stable nanoplexes with siRNA molecules, even in the presence of fetal bovine serum (FBS), and successfully assisted in vitro siRNA transfection in the non-adherent K562 cells. As a consequence of downregulation of BCR-ABL, BCPV-siRNA nanoplexes inhibited cell proliferation and promoted cell apoptosis. All results were compared with a commercial transfection reagent, Lipofectamine2000™, which served as a positive control. More importantly, this class of non-viral vector exhibits biodegradable features and negligible cytotoxicity, thus providing a versatile platform to deliver siRNA to non-adherent leukemia cells with high transfection efficiency by effectively overcoming extra- and intra-cellular barriers. Due to the excellent in vitro transfection results from BCPV-siRNA, a newly developed biodegradable transfection agent, BCPV, is being probed for transfection performance in an animal model.
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http://dx.doi.org/10.1039/c6nr00996dDOI Listing
April 2016

Synthesis and Characterization of Mn:ZnSe/ZnS/ZnMnS Sandwiched QDs for Multimodal Imaging and Theranostic Applications.

Small 2016 Jan 10;12(4):534-46. Epub 2015 Dec 10.

School of Electrical and Electronic Engineering, Nanyang Technological University, 50 Nanyang Avenue, 639798, Singapore.

In this work, a facile aqueous synthesis method is optimized to produce Mn:ZnSe/ZnS/ZnMnS sandwiched quantum dots (SQDs). In this core-shell co-doped system, paramagnetic Mn(2+) ions are introduced as core and shell dopants to generate Mn phosphorescence and enhance the magnetic resonance imaging signal, respectively. T1 relaxivity of the nanoparticles can be improved and manipulated by raising the shell doping level. Steady state and time-resolved optical measurements suggest that, after high level shell doping, Mn phosphorescence of the core can be sustained by the sandwiched ZnS shell. Because the SQDs are free of toxic heavy metal compositions, excellent biocompatibility of the prepared nanocrystals is verified by in vitro MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. To explore the theranostic applications of SQDs, liposome-SQD assemblies are prepared and used for ex vivo optical and magnetic resonance imaging. In addition, these engineered SQDs as nanocarrier for gene delivery in therapy of Panc-1 cancer cells are employed. The therapeutic effects of the nanocrystals formulation are confirmed by gene expression analysis and cell viability assay.
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http://dx.doi.org/10.1002/smll.201503352DOI Listing
January 2016

Exploring the amphiphilicity of PEGylated gold nanorods: mechanical phase transfer and self-assembly.

Chem Commun (Camb) 2013 Oct;49(81):9350-2

The Institute for Lasers, Photonics and Biophotonics, University at Buffalo-SUNY, Buffalo, New York 14260-3000, USA.

We introduce a mechanical approach to phase transfer of PEGylated gold nanorods. Amphiphilic PEG ligands can be switched between hydrophilic and hydrophobic states by applying mechanical force. PEG-GNRs in their hydrophobic state self-assemble into rings, a phenomenon previously observed only for GNRs capped with hydrophobic ligands.
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http://dx.doi.org/10.1039/c3cc45103hDOI Listing
October 2013

Au-Cu(2-x)Se heterodimer nanoparticles with broad localized surface plasmon resonance as contrast agents for deep tissue imaging.

Nano Lett 2013 Sep 30;13(9):4333-9. Epub 2013 Aug 30.

Department of Chemical and Biological Engineering, University at Buffalo (SUNY) , Buffalo, New York 14260, United States.

We report a new type of heterogeneous nanoparticles (NPs) composed of a heavily doped semiconductor domain (Cu2-xSe) and a metal domain (Au), which exhibit a broad localized surface plasmon resonance (LSPR) across visible and near-infrared (NIR) wavelengths, arising from interactions between the two nanocrystal domains. We demonstrate both in vivo photoacoustic imaging and in vitro dark field imaging, using the broad LSPR in Cu2-xSe-Au hybrid NPs to achieve contrast at different wavelengths. The high photoacoustic imaging depth achieved, up to 17 mm, shows that these novel contrast agents could be clinically relevant. More broadly, this work demonstrates a new strategy for tuning LSPR absorbance by engineering the density of free charge carriers in two interacting domains.
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http://dx.doi.org/10.1021/nl402124hDOI Listing
September 2013

Gene Silencing of Human Neuronal Cells for Drug Addiction Therapy using Anisotropic Nanocrystals.

Theranostics 2012 27;2(7):695-704. Epub 2012 Jul 27.

1. Institute for Lasers, Photonics and Biophotonics, University at Buffalo, State University of New York, Buffalo, NY 14260-4200, USA.

Theranostic platform integrating diagnostic imaging and therapeutic function into a single system has become a new direction of nanoparticle research. In the process of treatment, therapeutic efficacy is monitored. The use of theranostic nanoparticle can add an additional "layer" to keep track on the therapeutic agent such as the pharmacokinetics and biodistribution. In this report, we have developed quantum rod (QR) based formulations for the delivery of small interfering RNAs (siRNAs) to human neuronal cells. PEGlyated QRs with different surface functional groups (amine and maleimide) were designed for selectively down-regulating the dopaminergic signaling pathway which is associated with the drug abuse behavior. We have demonstrated that the DARPP-32 siRNAs were successfully delivered to dopaminergic neuronal (DAN) cells which led to drastic knockdown of specific gene expression by both the electrostatic and covalent bond conjugation regimes. The PEGlyated surface offered high biocompatibilities and negligible cytotoxicities to the QR formulations that may facilitate the in vivo applications of these nanoparticles.
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http://dx.doi.org/10.7150/thno.3459DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3418925PMC
October 2012

[The changes of soluble interleukin-2 receptor in serum and cerebrospinal fluid of patients with delayed encephalopathy after acute carbon monoxide poisoning].

Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi 2002 Oct;20(5):350-2

Department of Neurology, Second Affiliated Hospital of Xinxiang Medical College, Xinxiang, Henan 453002, China.

Objective: To explore the changes of soluble interleukin-2 receptor(sIL-2R) in serum and cerebrospinal fluid (CSF) of patients with delayed encephalopathy after acute carbon monoxide poisoning (DEACMP).

Methods: There were 31 patients with DEACMP, 32 patients with other encephalopathy and 31 controls in this study. The levels of sIL-2R in serum and CSF were detected by ELISA.

Results: Serum sIL-2R in patients with DEACMP[(329.21 +/- 160.99)U/ml] was significantly higher than that in control[(115.67 +/- 89.58) U/ml, P < 0.05)], but not significantly different from that in the other encephalopathy group[(367.50 +/- 123.14) U/ml, P > 0.05)]. CSF sIL-2R in patients with DEACMP[(54.48 +/- 43.04) U/ml] measured a little before discharge was significantly lower than that in patients with the other encephalopathy[(110.24 +/- 76.56) U/ml, P < 0.05)], but not significantly different from that in the control group[(34.96 +/- 22.70)U/ml, P > 0.05)]. At the pre-discharged period, CSF sIL-2R in patients with DEACMP[(100.26 +/- 93.65) U/ml] was significantly higher than that at the early stage of hospitalization[(52.28 +/- 43.31) U/ml, P < 0.05)]. No significant difference in serum sIL-2R was found between early stage of hospitalization[(338.34 +/- 161.53) U/ml] and pre-discharge [(351.31 +/- 175.93) U/ml, P > 0.05)].

Conclusion: The occurrence of DEACMP may be related with immunopathological damage. The sIL-2R levels in serum and CSF may give information about the state of immunological function of the patients with DEACMP and may contribute to determining the patient's condition and prognosis.
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October 2002