Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Oriented attachment of V_NAR proteins, via site-selective modification, on PLGA-PEG nanoparticles enhances nanoconjugate performance.

ABSTRACT: Herein we report the construction of a nanoparticle-based drug delivery system which targets a key regulator in tumour angiogenesis. We exploit a Variable New Antigen Receptor (VNAR) domain, conjugated using site-specific chemistry, to direct poly lactic acid-co-glycolic acid-polyethylene glycol (PLGA-PEG) nanoparticles to delta like canonical Notch ligand 4 (DLL4). The importance of site-specific chemistry is demonstrated.

SUBMITTER: Nogueira JCF

PROVIDER: S-EPMC6873773 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Oriented attachment of V<sub>NAR</sub> proteins, via site-selective modification, on PLGA-PEG nanoparticles enhances nanoconjugate performance.

Nogueira João C F JCF Greene Michelle K MK Richards Daniel A DA Furby Alexander O AO Steven John J Porter Andrew A Barelle Caroline C Scott Christopher J CJ Chudasama Vijay V

Chemical communications (Cambridge, England) 20190601 53

Herein we report the construction of a nanoparticle-based drug delivery system which targets a key regulator in tumour angiogenesis. We exploit a Variable New Antigen Receptor (VNAR) domain, conjugated using site-specific chemistry, to direct poly lactic acid-co-glycolic acid-polyethylene glycol (PLGA-PEG) nanoparticles to delta like canonical Notch ligand 4 (DLL4). The importance of site-specific chemistry is demonstrated. ...[more]

PMID: 31204425

Similar Datasets

PEG-b-PLA micelles and PLGA-b-PEG-b-PLGA sol-gels for drug delivery.

Project description:Poly(ethylene glycol)-block-poly(D,L-lactic acid) (PEG-b-PLA) micelles and poly(D,L-lactic-co-glycolic acid)-block-polyethylene glycol)-block-poly(D,L-lactic-co-glycolic acid) (PLGA-b-PEG-b-PLGA) sol-gels have been extensively researched for systemic and localized drug delivery applications, respectively, and they have both progressed into humans for paclitaxel, an important yet poorly water-soluble chemotherapeutic agent. In this review article, preclinical and clinical research on PEG-b-PLA micelles and PLGA-b-PEG-b-PLGA sol-gels that has focused on paclitaxel will be updated, and recent research on other poorly water-soluble anticancer agents and delivery of drug combinations (i.e. multi-drug delivery) that seeks synergistic anticancer efficacy will be summarized. PEG-b-PLA micelles are a first-generation platform for the systemic multi-delivery of poorly water soluble anticancer agents. PLGA-b-PEG-b-PLGA sol-gels are a first-generation platform for the localized multi-drug delivery of water-soluble and/or poorly water-soluble anticancer agents. In summary, PEG-b-PLA micelles and PLGA-b-PEG-b-PLGA sol-gels may safely enable pre-clinical evaluation and clinical translation of poorly water-soluble anticancer agents, especially for promising, rapidly emerging anticancer combinations.

| S-EPMC4909590 | biostudies-other

Lysozyme release and polymer erosion behavior of injectable implants prepared from PLGA-PEG block copolymers and PLGA/PLGA-PEG blends.

Project description:PurposeWe evaluated the controlled release of lysozyme from various poly(D,L-lactic-co-glycolic acid) (PLGA) 50/50-polyethylene glycol (PEG) block copolymers relative to PLGA 50/50.MethodsLysozyme was encapsulated in cylindrical implants (0.8 mm diameter) by a solvent extrusion method. Release studies were conducted in phosphate buffered saline +0.02% Tween 80 (PBST) at 37°C. Lysozyme activity was measured by a fluorescence-based assay. Implant erosion was evaluated by kinetics of polymer molecular weight decline, water uptake, and mass loss.ResultsLysozyme release from an AB15 di-block copolymer (15% 5 kDa PEG, PLGA 28 kDa) was very fast, whereas an AB10 di-block copolymer (with 10% 5 kDa PEG, PLGA 45 kDa) and ABA10 tri-block copolymer (with 10% 6 kDa PEG, PLGA 27 kDa) showed release profiles similar to PLGA. We achieved continuous lysozyme release for up to 4 weeks from AB10 and ABA10 by lysozyme co-encapsulation with the pore-forming and acid-neutralizing MgCO3, and from AB15 by co-encapsulation of MgCO3 and blending AB15 with PLGA. Lysozyme activity was mostly recovered during 4 weeks.ConclusionsThese block co-polymers may have utility either alone or as PLGA blends for the controlled release of proteins.

| S-EPMC3930621 | biostudies-literature

PEG-PLGA nanoparticles for encapsulating ciprofloxacin.

Project description:Antibiotic medications have been found to hinder the success of regenerative endodontic treatment due to the rapid degradation of the drug, and the acidic nature of ciprofloxacin (CIP) can be harmful to stem cells of the apical papilla (SCAPs), the cells responsible for regeneration. In this study, a nanocarrier system was used for controlled drug release for longer drug activity and less cytotoxicity to the cells. CIP was loaded in poly (ethylene glycol) methyl ether-block-poly (lactide-co-glycolide) (PEG-PLGA) nanoparticles (NPs) with an ion-pairing agent. The NPs demonstrated a monodispersed spherical morphology with a mean diameter of 120.7 ± 0.43 nm. The encapsulation efficiency of the CIP-loaded PEG-PLGA NPs was 63.26 ± 9.24%, and the loading content was 7.75 ± 1.13%. Sustained CIP release was achieved over 168 h and confirmed with theoretical kinetic models. Enhanced NP bactericidal activity was observed against Enterococcus faecalis. Additionally, CIP-loaded PEG-PLGA NPs had a low cytotoxic effect on SCAPs. These results suggest the use of a nanocarrier system to prolong the antibiotic activity, provide a sterile environment, and prevent reinfection by the bacteria remaining in the root canal during regenerative endodontic treatment.

| S-EPMC9822989 | biostudies-literature

Continual cell deformation induced via attachment to oriented fibers enhances fibroblast cell migration.

Project description:Fibroblast migration is critical to the wound healing process. In vivo, migration occurs on fibrillar substrates, and previous observations have shown that a significant time lag exists before the onset of granulation tissue. We therefore conducted a series of experiments to understand the impact of both fibrillar morphology and migration time. Substrate topography was first shown to have a profound influence. Fibroblasts preferentially attach to fibrillar surfaces, and orient their cytoplasm for maximal contact with the fiber edge. In the case of en-mass cell migration out of an agarose droplet, fibroblasts on flat surfaces emerged with an enhanced velocity, v = 52μm/h, that decreases to the single cell value, v = 28μm/h within 24 hours and remained constant for at least four days. Fibroblasts emerging on fibrillar surfaces emerged with the single cell velocity, which remained constant for the first 24 hours and then increased reaching a plateau with more than twice the initial velocity within the next three days. The focal adhesions were distributed uniformly in cells on flat surfaces, while on the fibrillar surface they were clustered along the cell periphery. Furthermore, the number of focal adhesions for the cells on the flat surfaces remained constant, while it decreased on the fibrillar surface during the next three days. The deformation of the cell nuclei was found to be 50% larger on the fiber surfaces for the first 24 hours. While the mean deformation remained constant on the flat surface, it increased for the next three days by 24% in cells on fibers. On the fourth day, large actin/myosin fibers formed in cells on fibrillar surfaces only and coincided with a change from the standard migration mechanism involving extension of lamellipodia, and retraction of the rear, to one involving strong contractions oriented along the fibers and centered about the nucleus.

| S-EPMC4361054 | biostudies-literature

Thermosensitive PLGA-PEG-PLGA Hydrogel as Depot Matrix for Allergen-Specific Immunotherapy.

Project description:Allergen-specific immunotherapy (AIT) is the only currently available curative treatment option for allergic diseases. AIT often includes depot-forming and immunostimulatory adjuvants, to prolong allergen presentation and to improve therapeutic efficacy. The use of aluminium salts in AIT, which are commonly used as depot-forming adjuvants, is controversially discussed, due to health concerns and Th2-promoting activity. Therefore, there is the need for novel delivery systems in AIT with similar therapeutic efficacy compared to classical AIT strategies. In this study, a triblock copolymer (hydrogel) was assessed as a delivery system for AIT in a murine model of allergic asthma. We show that the hydrogel combines the advantages of both depot function and biodegradability at the same time. We further demonstrate the suitability of hydrogel to release different bioactive compounds in vitro and in vivo. AIT delivered with hydrogel reduces key parameters of allergic inflammation, such as inflammatory cell infiltration, mucus hypersecretion, and allergen-specific IgE, in a comparable manner to standard AIT treatment. Additionally, hydrogel-based AIT is superior in inducing allergen-specific IgG antibodies with potentially protective functions. Taken together, hydrogel represents a promising delivery system for AIT that is able to combine therapeutic allergen administration with the prolonged release of immunomodulators at the same time.

| S-EPMC9329805 | biostudies-literature

Ultrasound-Mediated Cavitation Enhances EGFR-Targeting PLGA-PEG Nano-Micelle Delivery for Triple-Negative Breast Cancer Treatment.

Project description:Triple-negative breast cancer (TNBC) is highly recurring and metastatic breast cancer with overexpressing epidermal growth factor receptor (EGFR). Herein, a series of in vitro and in vivo analyses were used to explore the therapeutic effect of EGFR-targeting nano-micelles (PLGA-PEG/DOX@anti-EGFR) combined with ultrasound-mediated cavitation (UMC). The prepared nano-micelle drug carriers have good biocompatibility and can greatly increase the drug accumulation in tumor regions, thereby reducing off-target toxicity while enhancing anti-tumor efficacy. Moreover, an in vivo analysis of the practical utility of this treatment modality was conducted by using SonoVueTM microbubbles to achieve cavitation under different power intensity levels, with an ultrasonic power intensity of 0.5 W/cm2 maximizing the intra-tumoral blood perfusion. Relative to PLGA-PEG@DOX/anti-EGFR nano-micelles treatment alone, the combination with UMC was better able to suppress tumor growth even at low concentrations. As such, combining actively targeted drug-carrier molecules with UMC represents an effective approach to enhancing therapeutic efficacy while reducing the adverse, systemic effects associated with DOX and other chemotherapeutic drugs, and it can be considered as a promising clinical prospect in the treatment of TNBC.

| S-EPMC8304156 | biostudies-literature

Drug-loaded PEG-PLGA nanoparticles for cancer treatment.

Project description:Nanoparticles based on single-component synthetic polymers, such as poly (lactic acid-co-glycolic acid) (PLGA), have been extensively studied for antitumor drug delivery and adjuvant therapy due to their ability to encapsulate and release drugs, as well as passively target tumors. Amphiphilic block co-polymers, such as polyethylene glycol (PEG)-PLGA, have also been used to prepare multifunctional nanodrug delivery systems with prolonged circulation time and greater bioavailability that can encapsulate a wider variety of drugs, including small molecules, gene-targeting drugs, traditional Chinese medicine (TCM) and multi-target enzyme inhibitors, enhancing their antitumor effect and safety. In addition, the surface of PEG-PLGA nanoparticles has been modified with various ligands to achieve active targeting and selective accumulation of antitumor drugs in tumor cells. Modification with two ligands has also been applied with good antitumor effects, while the use of imaging agents and pH-responsive or magnetic materials has paved the way for the application of such nanoparticles in clinical diagnosis. In this work, we provide an overview of the synthesis and application of PEG-PLGA nanoparticles in cancer treatment and we discuss the recent advances in ligand modification for active tumor targeting.

| S-EPMC9437283 | biostudies-literature

Oriented Attachment and Nanorod Formation in Atomic Layer Deposition of TiO<sub>2</sub> on Graphene Nanoplatelets.

Project description:Understanding the spontaneous organization of atoms on well-defined surfaces promises to enable control over the shape and size of supported nanostructures. Atomic layer deposition (ALD) boasts atomic-scale control in the synthesis of thin films and nanoparticles. Yet, the possibility to control the shape of ALD-grown nanostructures remains mostly unexplored. Here, we report on the bottom-up formation of both linear and V-shaped anatase TiO2 nanorods (NRs) on graphene nanoplatelets during TiCl4/H2O ALD carried out at 300 °C. NRs as large as 200 nm form after only five ALD cycles, indicating that diffusional processes rather than layer-by-layer growth are behind the NR formation. In particular, high-resolution transmission electron microscopy reveals that the TiO2 NRs and graphene nanoplatelets are in rotational alignment as a result of lattice matching. Crucially, we also show that individual nanocrystals can undergo in-plane oriented attachment.

| S-EPMC6120748 | biostudies-literature

Co-delivery of paclitaxel and cisplatin with biocompatible PLGA-PEG nanoparticles enhances chemoradiotherapy in non-small cell lung cancer models.

Project description:Chemoradiotherapy (CRT) with paclitaxel (PTX) and cisplatin (CP) is part of the standard of care for patients with locally advanced non-small cell lung cancer (NSCLC). Despite the high treatment intensity, many patients still develop local recurrence after treatment. Thus, there is a strong need to further improve CRT for lung cancer. One strategy is to co-deliver cytotoxic chemotherapy agents using biocompatible nanoparticles (NPs) which can limit off-target tissue toxicity and improve therapeutic efficacy. Herein, we report the development of dual-drug loaded nanoformulations that improve the efficacy of CRT for NSCLC by co-encapsulation of cisplatin (CP) and PTX in PLGA-PEG NPs. Mice bearing NSCLC xenografts given the dual-drug loaded NPs during CRT showed greater inhibition of tumor growth than free drug combinations or combinations of single-drug loaded NPs. These results indicate that using a NP co-delivery strategy for this common CRT regimen may improve clinical responses in NSCLC patients.

| S-EPMC5576184 | biostudies-literature

Shape dependent cytotoxicity of PLGA-PEG nanoparticles on human cells.

Project description:We investigated the influence of nanoparticles' shape on the physiological responses of cells, when they were fed with spherical and needle-shaped PLGA-PEG nanoparticles (the volume of the nanoparticles had been chosen as the fixed parameter). We found that both types of NPs entered cells via endocytosis and upon internalization they stayed in membrane bounded vesicles. Needle-shaped, but not the spherical-shaped NPs were found to induce significant cytotoxicity in the cell lines tested. Our study evidenced that the cytotoxicity of needle-shaped NPs was induced through the lysosome disruption. Lysosome damage activated the signaling pathways for cell apoptosis, and eventually caused DNA fragmentation and cell death. The present work showed that physiological response of the cells can be very different when the shape of the fed nanoparticles changed from spherical to needle-like. The finding suggests that the toxicity of nanomaterials also depends on their shape.

| S-EPMC5544670 | biostudies-literature