794 results match your criteria degradable nanoparticles

An Overview of Nanocarrier-Based Adjuvants for Vaccine Delivery.

Pharmaceutics 2021 Mar 27;13(4). Epub 2021 Mar 27.

School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool L3 3AF, UK.

The development of vaccines is one of the most significant medical accomplishments which has helped to eradicate a large number of diseases. It has undergone an evolutionary process from live attenuated pathogen vaccine to killed whole organisms or inactivated toxins (toxoids), each of them having its own advantages and disadvantages. The crucial parameters in vaccination are the generation of memory response and protection against infection, while an important aspect is the effective delivery of antigen in an intelligent manner to evoke a robust immune response. Read More

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Design and Testing of Efficient Mucus-Penetrating Nanogels-Pitfalls of Preclinical Testing and Lessons Learned.

Small 2021 Mar 14:e2007963. Epub 2021 Mar 14.

Freie Universität Berlin, Institute for Pharmaceutical Sciences, Königin-Luise-Strasse 2-4, 14195, Berlin, Germany.

Mucosal surfaces pose a challenging environment for efficient drug delivery. Various delivery strategies such as nanoparticles have been employed so far; yet, still yielding limited success. To address the need of efficient transmucosal drug delivery, this report presents the synthesis of novel disulfide-containing dendritic polyglycerol (dPG)-based nanogels and their preclinical testing. Read More

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Natural rosin modified carboxymethyl cellulose delivery system with lowered toxicity for long-term pest control.

Carbohydr Polym 2021 May 4;259:117749. Epub 2021 Feb 4.

Innovative Institute for Plant Health, Key Laboratory of Agricultural Green Fine Chemicals of Guangdong Higher Education Institution, School of Chemistry and Chemical Engineering, Zhongkai University of Agriculture and Engineering, Guangzhou, Guangdong, 510225, People's Republic of China; Maoming Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Maoming, Guangdong, 525000, People's Republic of China. Electronic address:

The increasing world-wide demand for food has prompted the development of efficient and environmentally friendly pesticide formulations. In this article, we have prepared CMC-g-PRSG carrier based on two compounds from natural materials carboxymethyl cellulose (CMC) and rosin (RS). The model pesticide avermectin (AVM) was encapsulated through hydrophobic interaction, and self-assembled to form nanopesticide AVM@CMC-g-PRSG with an average particle size of 167 nm. Read More

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Systemic Immunotherapy with Micellar Resiquimod-Polymer Conjugates Triggers a Robust Antitumor Response in a Breast Cancer Model.

Adv Healthc Mater 2021 Mar 1:e2100008. Epub 2021 Mar 1.

Molecular Imaging Program at Stanford (MIPS), Department of Radiology, Stanford University, Palo Alto, CA, 94305, USA.

Resiquimod is an immunopotent toll-like receptor 7/8 agonist with antitumor activity. Despite being potent against skin cancers, it is poorly tolerated systemically due to toxicity. Integrating resiquimod into nanoparticles presents an avenue to circumvent the toxicity problem. Read More

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Responsive Degradable Theranostic Agents Enable Controlled Selenium Delivery to Enhance Photothermal Radiotherapy and Reduce Side Effects.

Adv Healthc Mater 2021 Feb 28:e2002024. Epub 2021 Feb 28.

College of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, Shanghai, 201620, China.

Radiotherapy (RT) is a popular clinical therapy method for extending cancer patient survival, but is hampered by severe side effects and the weak therapy effect. Herein, responsive degradable selenium (Se) theranostic agents (Se@SiO @Bi nanocomposites (NCs)) are fabricated, which combine computed tomography (CT) imaging and simultaneously enhance the therapeutic effects of photothermal therapy (PTT) and RT, while reducing the side effects of radiation. The Se@SiO @Bi theranostic agents can accumulate at the tumor site, and responsively decompose to releease Se, avoiding systemic toxicity by the element. Read More

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February 2021

Cryptobiosis-inspired assembly of "AND" logic gate platform for potential tumor-specific drug delivery.

Acta Pharm Sin B 2021 Feb 25;11(2):534-543. Epub 2020 Aug 25.

School of Food and Biological Engineering, School of Instrument Science and Opto-Electronics Engineering, Hefei University of Technology, Hefei 230009, China.

Developing tumor-specific drug delivery systems with minimized off-target cargo leakage remains an enduring challenge. In this study, inspired from the natural cryptobiosis explored by certain organisms and stimuli-responsive polyphenol‒metal coordination chemistry, doxorubicin (DOX)-conjugated gelatin nanoparticles with protective shells formed by complex of tannic acid and Fe (DG@TA-Fe NPs) were successfully developed as an "AND" logic gate platform for tumor-targeted DOX delivery. Moreover, benefiting from the well-reported photothermal conversion ability of TA-Fe complex, a synergistic tumor inhibition effect was confirmed by treating 4T1 tumor-bearing mice with DG@TA-Fe NPs and localized near-infrared (NIR) laser irradiation. Read More

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February 2021

Degradable Poly(vinyl alcohol)-Based Supramolecular Plastics with High Mechanical Strength in a Watery Environment.

Adv Mater 2021 Apr 26;33(13):e2007371. Epub 2021 Feb 26.

State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun, 130012, P. R. China.

It is challenging to fabricate degradable poly(vinyl alcohol) (PVA)-based plastics that can be used in watery environments because PVA is soluble in water. In this study, PVA-based supramolecular plastics with excellent degradability in soil and high mechanical strength in watery environments are fabricated by the complexation of vanillin-grafted PVA (VPVA), hydrophobic humic acid (HA), and Fe ions (hereafter denoted as VPVA-HA-Fe complexes). Large-area PVA-based plastics can be easily prepared from a solution of VPVA-HA-Fe complexes using a blade-coating method. Read More

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Merocyanine-paclitaxel conjugates for photothermal induced chemotherapy.

J Mater Chem B 2021 03;9(9):2334-2340

State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry Chinese Academy of Sciences, Changchun 130022, P. R. China. and University of Science and Technology of China, Hefei 230026, P. R. China.

Small molecular nanomedicines that integrate the flexibility of self-assembly strategies and the advantages of a precise molecular structure, a high drug content and controlled drug release are effective diagnostic and therapeutic modalities. Herein, merocyanine-paclitaxel conjugates (MC-PTX) were developed and fabricated by using the degradable ester bonds as the linker. The as-prepared MC-PTX could self-assemble into nanoparticles (MC-PTX NPs) using the non-covalent molecular interaction via the nanoprecipitation method. Read More

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Surface modification of polyurethane with eptifibatide-loaded degradable nanoparticles reducing risk of blood coagulation.

Colloids Surf B Biointerfaces 2021 May 13;201:111624. Epub 2021 Feb 13.

Department of Internal Medicine, Jagiellonian University Medical College, 8 Skawińska st., 31-066 Cracow, Poland.

The main purpose of the work was to develop a drug releasing coatings on the surface of medical devices exposed to blood flow, what should enable effective inhibition of blood coagulation process. As a part of the work, the process of encapsulating the anticoagulant drug eptifibatide (EPT) in poly(DL-lactic-co-glycolic acid) (PLGA) nanoparticles was developed. EPT encapsulation efficiency was 29. Read More

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Hydrogen peroxide-responsive platelet membrane-coated nanoparticles for thrombus therapy.

Biomater Sci 2021 Apr 22;9(7):2696-2708. Epub 2021 Feb 22.

Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI 53715, USA.

Occlusion of blood vessels caused by thrombi is the major pathogenesis of various catastrophic cardiovascular diseases. Thrombi can be prevented or treated by antithrombotic drugs. However, free antithrombotic drugs often have relatively low therapeutic efficacy due to a number of limitations such as short half-life, unexpected bleeding complications, low thrombus targeting capability, and negligible hydrogen peroxide (HO)-scavenging ability. Read More

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Biodegradable Silica-Based Nanotheranostics for Precise MRI/NIR-II Fluorescence Imaging and Self-Reinforcing Antitumor Therapy.

Small 2021 Mar 11;17(10):e2006508. Epub 2021 Feb 11.

Department of Radiology, third hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Taiyuan, 030032, China.

Multi-modality cancer diagnosis techniques based on the second near-infrared window fluorescence (NIR-II FL, 1000-1700 nm) imaging have become the focus of research attention. For such multimodality probes, how to take advantage of the tumor microenvironments (TME) characteristics to better image diseases and combine efficient therapeutics to achieve theranostics is still a big challenge. Herein, a novel TME-activated nanosystem (FMSN-MnO -BCQ) employing degradable silica-based nanoplatform is designed, adjusting the ratio of intratumoral hydrogen peroxide (H O )/glutathione (GSH) for magnetic resonance imaging (MRI)/NIR-II FL imaging and self-reinforcing chemodynamic therapy (CDT). Read More

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CD47 Functionalization of Nanoparticles as a Poly(ethylene glycol) Alternative: A Novel Approach to Improve Drug Delivery.

Curr Drug Targets 2021 Feb 4. Epub 2021 Feb 4.

Department of Medical Biotechnology, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, . Iran.

Bio-degradable nanoparticles (NPs) have several utilizations as the drug delivery vehicles due to their acceptable bio-availability, lower toxicity, potency for encapsulation and controlled release. Moreover, interaction of the NPs with the macrophages of reticuloendothelial system (RES) may decrease NPs efficacy for medical purposes. The surface of NPs is conventionally neutralized with the molecules such as poly(ethylene glycol) (PEG), as one of the most widely applied stealth polymers, in order to restrict the NPs clearance through the RES system. Read More

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February 2021

Biodegradable FeWO nanoparticles for CT/MR imaging-guided synergistic photothermal, photodynamic, and chemodynamic therapy.

Nanoscale 2021 Feb 29;13(5):3049-3060. Epub 2021 Jan 29.

Research Center for Bioengineering and Sensing Technology, School of Chemistry and Bioengineering, University of Science & Technology Beijing, 30 Xueyuan Road, Beijing 100083, P. R. China.

The development of a simple and effective single constituent multifunctional nanotheranostic platform producing a multimodality diagnostic signal and curing effect is still a challenge. Herein, we synthesized simple and biodegradable FeWO ternary oxide nanoparticles and modified their surface with RGD-PEG-NH (FeWO-PEG-RGD NPs), whereby resulting NPs possessed a (T/T) switchable MRI/CT dual-modal imaging ability and synergistic photothermal therapy (PTT)/photodynamic therapy (PDT)/chemodynamic therapy (CDT) capacity. We showed that FeWO-PEG-RGD NPs enabled tumor accumulation under a magnetic field drive and RGD-mediated tumor penetration and implemented PTT/PDT treatment under 980 nm laser irradiation. Read More

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February 2021

(Bio)nanotechnology in Food Science-Food Packaging.

Nanomaterials (Basel) 2021 Jan 22;11(2). Epub 2021 Jan 22.

Faculty of Chemistry and Chemical Engineering, University of Maribor, Smetanova 17, 2000 Maribor, Slovenia.

Bionanotechnology, as a tool for incorporation of biological molecules into nanoartifacts, is gaining more and more importance in the field of food packaging. It offers an advanced expectation of food packaging that can ensure longer shelf life of products and safer packaging with improved food quality and traceability. This review recent focuses on advances in food nanopackaging, including bio-based, improved, active, and smart packaging. Read More

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January 2021

Sericin based nanoformulations: a comprehensive review on molecular mechanisms of interaction with organisms to biological applications.

J Nanobiotechnology 2021 Jan 22;19(1):30. Epub 2021 Jan 22.

Research Institute of Biotechnology & Medical Converged Science, Dongguk University-Seoul, Goyangsi, 10326, Republic of Korea.

Background: The advances in products based on nanotechnology have directed extensive research on low-cost, biologically compatible, and easily degradable materials.

Main Body: Sericin (SER) is a protein mainly composed of glycine, serine, aspartic acid, and threonine amino acids removed from the silkworm cocoon (particularly Bombyx mori and other species). SER is a biocompatible material with economic viability, which can be easily functionalized due to its potential crosslink reactions. Read More

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January 2021

Degradable and colloidally stable zwitterionic-functionalized silica nanoparticles.

Nanomedicine (Lond) 2021 01 19;16(2):85-96. Epub 2021 Jan 19.

Laboratório Nacional de Nanotecnologia (LNNano), Centro Nacional de Pesquisa em Energia e Materiais (CNPEM), Campinas, SP, CEP 13083 970, Brasil.

This work is focused on obtaining degradable mesoporous silica nanoparticles (DMSNs) which are able to maintain their colloidal stability in complex biological media. DMSNs were synthesized using different ratios of disulfide organosilane (degradable structural moiety) and further functionalized with sulfobetaine silane (SBS) to enhance colloidal stability and improve biological compatibility. There was a clear trade-off between nanoparticle degradability and colloidal stability, since full optimization of the degradation process generated unstable particles, while enhancing colloidal stability resulted in poor DMSNs degradation. Read More

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January 2021

Acid-Responsive and Biologically Degradable Polyphosphazene Nanodrugs for Efficient Drug Delivery.

ACS Biomater Sci Eng 2020 07 15;6(7):4285-4293. Epub 2020 Jun 15.

School of Science, MOE Key Laboratory for Nonequilibrium Synthesis and Modulation of Condensed Matter, Xi'an Jiaotong University, Xi'an 710049, China.

To enhance the therapeutic effects and reduce the damage to normal tissues in cancer chemotherapy, it is indispensable to develop drug delivery carriers with controllable release and good biocompatibility. In this work, acid-responsive and degradable polyphosphazene (PPZ) nanoparticles were synthesized by the reaction of hexachlorotripolyphosphonitrile (HCCP) with 4-hydroxy-benzoic acid (4-hydroxy-benzylidene)-hydrazide (HBHBH) and anticancer drug doxorubicin (DOX). The controlled release of DOX could be realized based on the acid responsiveness of acylhydrazone in HBHBH. Read More

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CD44-Mediated Methotrexate Delivery by Hyaluronan-Coated Nanoparticles Composed of a Branched Cell-Penetrating Peptide.

ACS Biomater Sci Eng 2020 01 27;6(1):494-504. Epub 2019 Dec 27.

Department of Chemical and Biomolecular Engineering, Yonsei University, Seoul 03722, Republic of Korea.

Branched polymers as drug delivery carriers have been widely attempted due to their outstanding drug loading capability and complex stability like branched polyethyleneimine (B-PEI). However, branched polymers without biodegradability may cause toxicity as they can accumulate in the body. Herein, we report branched modified nona-arginine (B-mR9) composed of redox-cleavable disulfide bonds to form stable complexes with methotrexate (MTX) as an anticancer agent, which is further coated with hyaluronic acid (HA). Read More

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January 2020

Degradable Spirocyclic Polyacetal-Based Core-Amphiphilic Assemblies for Encapsulation and Release of Hydrophobic Cargo.

Nanomaterials (Basel) 2021 Jan 10;11(1). Epub 2021 Jan 10.

Department of Chemistry, Université du Québec à Montréal, C.P.8888, Succursale Centre-Ville, Montréal, QC H3C 3P8, Canada.

Polymeric nanomaterials that degrade in acidic environments have gained considerable attention in nanomedicine for intracellular drug delivery and cancer therapy. Among various acid-degradable linkages, spirocyclic acetals have rarely been used to fabricate such vehicles. In addition to acid sensitivity, they benefit from conformational rigidity that is otherwise not attainable by their non-spirocyclic analogs. Read More

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January 2021

Gums-based engineered bio-nanostructures for greening the 21st-century biotechnological settings.

Crit Rev Food Sci Nutr 2021 Jan 11:1-17. Epub 2021 Jan 11.

Tecnologico de Monterrey, School of Engineering and Sciences, Monterrey, Mexico.

Naturally occurring plant-based gums and their engineered bio-nanostructures have gained an immense essence of excellence in several industrial, biotechnological, and biomedical sectors of the modern world. Gums derived from bio-renewable resources that follow green chemistry principles are considered green macromolecules with unique structural and functional attributes. For instance, gum mostly obtained as exudates are bio-renewable, bio-degradable, bio-compatible, sustainable, overall cost-effective, and nontoxic. Read More

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January 2021

Nanoparticle-mediated gene therapy strategies for mitigating inflammatory bowel disease.

Biomater Sci 2021 Mar;9(5):1481-1502

Laboratory of Nanotechnology and Chemical Biology, Regional Centre for Biotechnology, NCR Biotech Science Cluster, 3rd Milestone Faridabad-Gurgaon Expressway, Faridabad-121001, Haryana, India.

Inflammatory bowel disease (IBD) is an autoimmune disorder of the gastrointestinal tract (GIT) where Ulcerative Colitis (UC) displays localized inflammation in the colon, and Crohn's Disease (CD) affects the entire GIT. Failure of current therapies and associated side-effects bring forth serious social, economic, and health challenges. The gut epithelium provides the best target for gene therapy delivery vehicles to combat IBD. Read More

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In situ-gelling starch nanoparticle (SNP)/O-carboxymethyl chitosan (CMCh) nanoparticle network hydrogels for the intranasal delivery of an antipsychotic peptide.

J Control Release 2021 Feb 28;330:738-752. Epub 2020 Dec 28.

Department of Chemical Engineering, McMaster University, 1280 Main Street, West Hamilton, ON L8S 4L8, Canada. Electronic address:

Existing oral or injectable antipsychotic drug delivery strategies typically demonstrate low bioavailability to targeted brain regions, incentivizing the development of alternative delivery strategies. Delivery via the nasal cavity circumvents multiple barriers for reaching the brain but requires drug delivery vehicles with very specific properties to be effective. Herein, we report in situ-gelling and degradable bulk nanoparticle network hydrogels consisting of oxidized starch nanoparticles (SNPs) and carboxymethyl chitosan (CMCh) that enable intranasal delivery via spray, high nasal mucosal retention, and functional controlled release of the peptide drug PAOPA, a positive allosteric modulator of dopamine D2 receptor. Read More

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February 2021

Biodegradable Poly(Lactic Acid) Nanocomposites for Fused Deposition Modeling 3D Printing.

Nanomaterials (Basel) 2020 Dec 21;10(12). Epub 2020 Dec 21.

Department of Chemistry and Macromolecules Innovation Institute, Virginia Tech, Blacksburg, VA 24061, USA.

3D printing by fused deposition modelling (FDM) enables rapid prototyping and fabrication of parts with complex geometries. Unfortunately, most materials suitable for FDM 3D printing are non-degradable, petroleum-based polymers. The current ecological crisis caused by plastic waste has produced great interest in biodegradable materials for many applications, including 3D printing. Read More

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December 2020

Poly(lipoic acid)-Based Nanoparticles as Self-Organized, Biocompatible, and Corona-Free Nanovectors.

Biomacromolecules 2021 Feb 21;22(2):467-480. Epub 2020 Dec 21.

Dipartimento di Scienze Chimiche, Università di Padova, via Marzolo 1, Padova, I-35131, Italy.

Herein we present an innovative approach to produce biocompatible, degradable, and stealth polymeric nanoparticles based on poly(lipoic acid), stabilized by a PEG-ended surfactant. Taking advantage of the well-known thiol-induced polymerization of lipoic acid, a universal and nontoxic nanovector consisted of a solid cross-linked polymeric matrix of lipoic acid monomers was prepared and loaded with active species with a one-step protocol. The biological studies demonstrated a high stability in biological media, the virtual absence of "protein" corona in biological fluids, the absence of acute toxicity in vitro and in vivo, complete clearance from the organism, and a relevant preference for short-term accumulation in the heart. Read More

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February 2021

Treatment of Colon Cancer by Degradable rrPPC Nano-Conjugates Delivered STAT3 siRNA.

Int J Nanomedicine 2020 7;15:9875-9890. Epub 2020 Dec 7.

Department of Pharmacy, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Personalized Drug Therapy Key Laboratory of Sichuan Province, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, People's Republic of China.

Background: Drugs that work based on the mechanism of RNA interference have shown strong potential in cancer gene therapy. Although significant progress has been made in small interfering RNA (siRNA) design and manufacturing, ideal delivery system remains a limitation for the development of siRNA-based drugs. Particularly, it is necessary to focus on parameters including delivery efficiency, stability, and safety when developing siRNA formulations for cancer therapy. Read More

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December 2020

Disulfiram-loaded functionalized magnetic nanoparticles combined with copper and sodium nitroprusside in breast cancer cells.

Mater Sci Eng C Mater Biol Appl 2021 Feb 27;119:111452. Epub 2020 Aug 27.

Department of Analytical Chemistry, Faculty of Pharmacy, Atatürk University, 25240 Erzurum, Turkey.

Disulfiram (DSF), one of the members of the dithiocarbamate family, is a reactive species (RS) generator and is capable of inducing cancer cell death in breast cancer. However, it is hydrophobic and highly degradable in blood. Therefore, drug delivery systems would be of great benefit in supporting the selective accumulation of DSF in tumor cells. Read More

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February 2021

Using MgO nanoparticles as a potential platform to precisely load and steadily release Ag ions for enhanced osteogenesis and bacterial killing.

Mater Sci Eng C Mater Biol Appl 2021 Feb 22;119:111399. Epub 2020 Aug 22.

State Key Laboratory of Powder Metallurgy, Central South University, Changsha 410083, PR China. Electronic address:

Bio-functional fillers including bio-ceramic, degradable metallic and composite particles are commonly introduced into bone tissue engineering (BTE) scaffolds to endow the materials with specific biological functions for enhanced bone defect therapy. In this work, MgO nanoparticles (NPs) were employed as a potential platform for precise loading and sustained release of Ag. The results showed that MgO NPs possessed strong adsorption capacity (almost 100%) towards Ag in AgNO solutions with different concentrations (0. Read More

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February 2021

Fabrication of Anisotropic Cu Ferrite-Polymer Core-Shell Nanoparticles for Photodynamic Ablation of Cervical Cancer Cells.

Nanomaterials (Basel) 2020 Dec 4;10(12). Epub 2020 Dec 4.

Department of Applied Chemistry, National Pingtung University, Pingtung 90003, Taiwan.

In this work we developed methylene blue-immobilized copper-iron nanoparticles (MB-CuFe NPs) through a facile one-step hydrothermal reaction to achieve a better phototherapeutic effect. The Fe/Cu ratio of the CuFe NPs was controllable by merely changing the loading amount of iron precursor concentration. The CuFe NPs could serve as a Fenton catalyst to convert hydrogen peroxide (HO) into reactive oxygen species (ROS), while the superparamagnetic properties also suggest magnetic resonance imaging (MRI) potential. Read More

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December 2020

Dextran-Based Nanoparticles to Formulate pH-Responsive Pickering Emulsions: A Fully Degradable Vector at a Day Scale.

Biomacromolecules 2020 12 3;21(12):5358-5368. Epub 2020 Dec 3.

Laboratoire de Chimie des Polymères Organiques, University Bordeaux, CNRS, Bordeaux INP, UMR 5629, Bordeaux, 16 Avenue Pey-Berland, 33607 Pessac, France.

Biosourced Pickering emulsion stabilizers with stimuli responsiveness are mostly designed for recycling and do not offer fast degradability as required for drug-delivery applications. Herein, dextran-a hydrophilic and biofriendly polysaccharide obtainable from biomass recovery-was used for the first time as a brick material for the formulation of (bio)degradable pH-sensitive Pickering emulsions. It was first modified with hydrophobic acetal moieties to provide pH-sensitive acetalated dextran. Read More

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December 2020

Cellular uptake of polymeric nanoparticles by bovine cumulus-oocyte complexes and their effect on in vitro developmental competence.

Eur J Pharm Biopharm 2021 Jan 25;158:143-155. Epub 2020 Nov 25.

Gamete Research Centre, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, 2610 Wilrijk, Belgium; Departement of Theriogenology, Faculty of Veterinary Medicine, Cairo University, Giza 12211, Egypt. Electronic address:

Polymeric nanoparticles (NPs) are produced using bio-compatible and bio-degradable materials such as PLGA (Poly(lactic-co-glycolic acid)). This technology provides a valuable tool to deliver molecules to the subcellular level with a relatively low risk of cytotoxicity. However their use in the field of reproductive biotechnology is not yet scientifically substantiated. Read More

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January 2021