Browse
Submit Data
Databases
API
Help

Dataset Information

25 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Light-Responsive Polymeric Micellar Nanoparticles with Enhanced Formulation Stability.

ABSTRACT: Light-sensitive polymeric micelles have recently emerged as promising drug delivery systems for spatiotemporally controlled release of payload at target sites. Here, we developed diazonaphthoquinone (DNQ)-conjugated micellar nanoparticles that showed a change in polarity of the micellar core from hydrophobic to hydrophilic under UV light, releasing the encapsulated anti-cancer drug, doxetaxel (DTX). The micelles exhibited a low critical micelle concentration and high stability in the presence of bovine serum albumin (BSA) solution due to the hydrophobic and ?-? stacking interactions in the micellar core. Cell studies showed enhanced cytotoxicity of DTX-loaded micellar nanoparticles upon irradiation. The enhanced stability would increase the circulation time of the micellar nanoparticles in blood, and enhance the therapeutic effectiveness for cancer therapy.

SUBMITTER: Kim KN

PROVIDER: S-EPMC7866127 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Light-Responsive Polymeric Micellar Nanoparticles with Enhanced Formulation Stability.

Kim Kyoung Nan KN Oh Keun Sang KS Shim Jiwook J Schlaepfer Isabel R IR Karam Sana D SD Lee Jung-Jae JJ

Polymers 20210126 3

Light-sensitive polymeric micelles have recently emerged as promising drug delivery systems for spatiotemporally controlled release of payload at target sites. Here, we developed diazonaphthoquinone (DNQ)-conjugated micellar nanoparticles that showed a change in polarity of the micellar core from hydrophobic to hydrophilic under UV light, releasing the encapsulated anti-cancer drug, doxetaxel (DTX). The micelles exhibited a low critical micelle concentration and high stability in the presence of ...[more]

PMID: 33530388

Similar Datasets

Fluorogenic Enzyme-Responsive Micellar Nanoparticles.

Project description:In this paper we describe enzyme-responsive fluorogenic micellar nanoparticles with detectable spectrophotometric properties unique to the particles and their aggregated state. These micelles are assembled from peptide-polymer amphiphiles (PPAs) labeled with either fluorescein or rhodamine. This is achieved by labelling otherwise similar block copolymer amphiphiles with each of the dyes. When mixed together, signals from the FRET-pairs can be utilized to detect particle assembly and hence enzymatic activity. Furthermore, we show FRET signals within the shell of the assembled micelles can be used to estimate particle stability (critical aggregation concentration) and enable a determination of intraparticle distances between amphiphiles in the micellar aggregates leading to elucidation of the packing arrangement of amphiphilic copolymers within the micelles.

| S-EPMC3622269 | biostudies-literature

pH-responsive high stability polymeric nanoparticles for targeted delivery of anticancer therapeutics.

Project description:The practical application of nanoparticles (NPs) as chemotherapeutic drug delivery systems is often hampered by issues such as poor circulation stability and targeting inefficiency. Here, we have utilized a simple approach to prepare biocompatible and biodegradable pH-responsive hybrid NPs that overcome these issues. The NPs consist of a drug-loaded polylactic-co-glycolic acid (PLGA) core covalently 'wrapped' with a crosslinked bovine serum albumin (BSA) shell designed to minimize interactions with serum proteins and macrophages that inhibit target recognition. The shell is functionalized with the acidity-triggered rational membrane (ATRAM) peptide to facilitate internalization specifically into cancer cells within the acidic tumor microenvironment. Following uptake, the unique intracellular conditions of cancer cells degrade the NPs, thereby releasing the chemotherapeutic cargo. The drug-loaded NPs showed potent anticancer activity in vitro and in vivo while exhibiting no toxicity to healthy tissue. Our results demonstrate that the ATRAM-BSA-PLGA NPs are a promising targeted cancer drug delivery platform.

| S-EPMC7054360 | biostudies-literature

Polymeric Nanoparticles with ROS-Responsive Prodrug and Platinum Nanozyme for Enhanced Chemophotodynamic Therapy of Colon Cancer.

Project description:The combination of chemotherapy and photodynamic therapy (PDT) has promising potential in the synergistic treatment of cancer. However, chemotherapy and photodynamic synergistic therapy are impeded by uncontrolled chemotherapeutics release behavior, targeting deficiencies, and hypoxia-associated poor PDT efficacy in solid tumors. Here, a platinum nanozyme (PtNP) loaded reactive oxygen species (ROS)-responsive prodrug nanoparticle (CPT-TK-HPPH/Pt NP) is created to overcome these limitations. The ROS-responsive prodrug consists of a thioketal bond linked with camptothecin (CPT) and photosensitizer-2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH). The PtNP in CPT-TK-HPPH/Pt NP can efficiently catalyze the decomposition of hydrogen peroxide (H2O2) into oxygen to relieve hypoxia. The production of oxygen can satisfy the consumption of HPPH under 660 nm laser irradiation to attain the on-demand release of CPT and ensure enhanced photodynamic therapy. As a tumor diagnosis agent, the results of photoacoustic imaging and fluorescence imaging for CPT-TK-HPPH/Pt NP exhibit desirable long circulation and enhanced in vivo targeting. CPT-TK-HPPH/Pt NPs effectively inhibit tumor proliferation and growth in vitro and in vivo. CPT-TK-HPPH/Pt NP, with its excellent ROS-responsive drug release behavior and enhanced PDT efficiency can serve as a new cancer theranostic agent, and will further promote the research of chemophotodynamic synergistic cancer therapy.

| S-EPMC7578901 | biostudies-literature

Micellar Formulation of Talazoparib and Buparlisib for Enhanced DNA Damage in Breast Cancer Chemoradiotherapy.

Project description:Chemoradiation is an effective combined modality therapeutic approach that utilizes principles of spatial cooperation to combat the adaptability associated with cancer and to potentially expand the therapeutic window. Optimal therapeutic efficacy requires intelligent selection and refinement of radiosynergistic pharmaceutical agents, enhanced delivery methods, and temporal consideration. Here, a monodisperse sub-20 nm mixed poloxamer micelle (MPM) system was developed to deliver hydrophobic drugs intravenously, in tandem with ionizing radiation. This report demonstrates in vitro synergy and enhanced radiosensitivity when two molecularly targeted DNA repair inhibitors, talazoparib and buparlisib, are encapsulated and combined with radiation in a 4T1 murine breast cancer model. Evaluation of in vivo biodistribution and toxicity exhibited no reduction in particle accumulation upon radiation and a lack of both acute and chronic toxicities. In vivo efficacy studies suggested the promise of combining talazoparib, buparlisib, and radiation to enhance survival and control tumor growth. Tissue analysis suggests enhanced DNA damage leading to apoptosis, thus increasing efficacy. These findings highlight the challenges associated with utilizing clinically relevant inclusion criteria and treatment protocols because complete tumor regression and extended survival were masked by an aggressively metastasizing model. As with clinical treatment regimens, the findings here establish a need for further optimization of this multimodal platform.

| S-EPMC7213279 | biostudies-literature

An in vivo mechanism for the reduced peripheral neurotoxicity of NK105: a paclitaxel-incorporating polymeric micellar nanoparticle formulation.

Project description:In our previous rodent studies, the paclitaxel (PTX)-incorporating polymeric micellar nanoparticle formulation NK105 had showed significantly stronger antitumor effects and reduced peripheral neurotoxicity than PTX dissolved in Cremophor® EL and ethanol (PTX/CRE). Thus, to elucidate the mechanisms underlying reduced peripheral neurotoxicity due to NK105, we performed pharmacokinetic analyses of NK105 and PTX/CRE in rats. Among neural tissues, the highest PTX concentrations were found in the dorsal root ganglion (DRG). Moreover, exposure of DRG to PTX (Cmax_PTX and AUC0-inf._PTX) in the NK105 group was almost half that in the PTX/CRE group, whereas exposure of sciatic and sural nerves was greater in the NK105 group than in the PTX/CRE group. In histopathological analyses, damage to DRG and both peripheral nerves was less in the NK105 group than in the PTX/CRE group. The consistency of these pharmacokinetic and histopathological data suggests that high levels of PTX in the DRG play an important role in the induction of peripheral neurotoxicity, and reduced distribution of PTX to the DRG of NK105-treated rats limits the ensuing peripheral neurotoxicity. In further analyses of PTX distribution to the DRG, Evans blue (Eb) was injected with BODIPY®-labeled NK105 into rats, and Eb fluorescence was observed only in the DRG. Following injection, most Eb dye bound to albumin particles of ~8 nm and had penetrated the DRG. In contrast, BODIPY®-NK105 particles of ~90 nm were not found in the DRG, suggesting differential penetration based on particle size. Because PTX also circulates as PTX-albumin particles of ~8 nm following injection of PTX/CRE, reduced peripheral neurotoxicity of NK105 may reflect exclusion from the DRG due to particle size, leading to reduced PTX levels in rat DRG (275).

| S-EPMC5317268 | biostudies-literature

A facile strategy for fine-tuning the stability and drug release of stimuli-responsive cross-linked micellar nanoparticles towards precision drug delivery.

Project description:Precision drug delivery has a great impact on the application of precision oncology for better patient care. Here we report a facile strategy for fine-tuning the stability, drug release and responsiveness of stimuli-responsive cross-linked nanoparticles towards precision drug delivery. A series of micellar nanoparticles with different levels of intramicellar disulfide crosslinkages could be conveniently produced with a mixed micelle approach. These micellar nanoparticles were all within a size range of 25-40 nm so that they could take full advantage of the enhanced permeability and retention (EPR) effect for tumor-targeted drug delivery. The properties of these nanoparticles such as critical micelle concentration (CMC), stability, drug release and responsiveness to a reductive environment could be well correlated with the levels of crosslinking (LOC). Compared to the micellar nanoparticles with a LOC at 0% that caused the death of animals of two species (mouse and rat) due to the acute toxicity such as hemolysis, the nanoparticles at all other levels of crosslinking were much safer to be administered into animals. The in vitro antitumor efficacy of micellar nanoparticles crosslinked at lower levels (20% & 50%) were much more effective than that of 100% crosslinked micellar nanoparticles in SKOV-3 ovarian cancer cells.

| S-EPMC5568647 | biostudies-literature

Tumor-Acidity Responsive Polymeric Nanoparticles for Targeting Delivery of Angiogenesis Inhibitor for Enhanced Antitumor Efficacy With Decreased Toxicity.

Project description:Various nanocarriers with tumor targeting ability and improved pharmacokinetic property have been extensively utilized to reduce the toxicity of existing clinical chemotherapeutics. Herein, we showed that by encapsulating angiogenesis inhibitor anlotinib into polymeric nanoparticles, we could significantly decrease its in vivo toxicity. The introduction of pH-responsiveness into the nanocarrier further enhanced its anti-tumor activity. Systemic administration of the anlotinib-loaded nanocarrier into mice bearing A549 and 4T1 subcutaneous tumor received a higher tumor growth suppression and metastasis inhibition without detectable side effects. This strategy offers a promising option to improve the patient compliance of anlotinib.

| S-EPMC8024478 | biostudies-literature

Matrix Metalloproteinase Responsive, Proximity-activated Polymeric Nanoparticles for siRNA Delivery.

Project description:Small interfering RNA (siRNA) has significant potential to evolve into a new class of pharmaceutical inhibitors, but technologies that enable robust, tissue-specific intracellular delivery must be developed before effective clinical translation can be achieved. A pH-responsive, smart polymeric nanoparticle (SPN) with matrix metalloproteinase (MMP)-7-dependent proximity-activated targeting (PAT) is described here. The PAT-SPN was designed to trigger cellular uptake and cytosolic delivery of siRNA once activated by MMP-7, an enzyme whose overexpression is a hallmark of cancer initiation and progression. The PAT-SPN is composed of a corona-forming PEG block, an MMP-7-cleavable peptide, a cationic siRNA-condensing block, and a pH-responsive, endosomolytic terpolymer block that drives self-assembly and forms the PAT-SPN core. With this novel design, the PEG corona shields cellular interactions until it is cleaved in MMP-7-rich environments, shifting SPN?-potential from +5.8 to +14.4 mV and triggering a 2.5 fold increase in carrier internalization. The PAT-SPN exhibited pH-dependent membrane disruptive behavior that enabled siRNA escape from endo-lysosomal pathways. Efficient intracellular siRNA delivery and knockdown of the model enzyme luciferase in R221A-Luc mammary tumor cellssignificantly depended on MMP-7 pre-activation. These combined data indicate that the PAT-SPN provides a promising new platform for tissue-specific, proximity-activated siRNA delivery to MMP-rich pathological environments.

| S-EPMC4159188 | biostudies-literature

Phosphorescent Pt(ii) complexes spatially arrayed in micellar polymeric nanoparticles providing dual readout for multimodal imaging.

Project description:In this paper we report phosphorescent Pt(ii) complexes as monomers which can be directly incorporated into growing polymers. Due to the amphiphilic nature of the polymers they can self-assemble into micellar nanoparticles, where the phosphorescent Pt(ii) complexes can arrange selectively in the core or shell of the nanoparticles. The complexes enable dual orthogonal imaging, made possible by the heavy metal, which enhances the contrast for these micelles in electron microscopy and facilitates spin-orbit coupling that turns on microsecond lifetime luminescence.

| S-EPMC6462434 | biostudies-literature

Rapamycin-Loaded Polymeric Nanoparticles as an Advanced Formulation for Macrophage Targeting in Atherosclerosis.

Project description:Recently, rapamycin (Rapa) represents a potential drug treatment to induce regression of atherosclerotic plaques; however, its use requires site-specific accumulation in the vessels involved in the formation of the plaques to avoid the systemic effects resulting from its indiscriminate biodistribution. In this work, a stable pharmaceutical formulation for Rapa was realized as a dried powder to be dispersed extemporaneously before administration. The latter was constituted by mannitol (Man) as an excipient and a Rapa-loaded polymeric nanoparticle carrier. These nanoparticles were obtained by nanoprecipitation and using as a starting polymeric material a polycaprolactone (PCL)/α,β-poly(N-2-hydroxyethyl)-dl-aspartamide (PHEA) graft copolymer. To obtain nanoparticles targeted to macrophages, an oxidized phospholipid with a high affinity for the CD36 receptor of macrophages, the 1-(palmitoyl)-2-(5-keto-6-octene-dioyl) phosphatidylcholine (KOdia-PC), was added to the starting organic phase. The chemical-physical and technological characterization of the obtained nanoparticles demonstrated that: both the drug loading (DL%) and the entrapment efficiency (EE%) entrapped drug are high; the entrapped drug is in the amorphous state, protected from degradation and slowly released from the polymeric matrix; and the KOdia-PC is on the nanoparticle surface (KP-Nano). The biological characterization demonstrated that both systems are quickly internalized by macrophages while maintaining the activity of the drug. In vitro studies demonstrated that the effect of KP-Nano Rapa-loaded, in reducing the amount of the Phospo-Ser757-ULK1 protein through the inhibition of the mammalian target of rapamycin (mTOR), is comparable to that of the free drug.

| S-EPMC8067637 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data