Preparation of pH and redox dual-sensitive core crosslinked micelles for overcoming drug resistance of DOX

Yi, Xiaoqing; Zhang, Quan; Zhao, Dan; Xu, Jiaqi; Zhong, Zhang; Zhuo, Ren‐Xi; Li, Feng

doi:10.1039/c5py01783a

Cited by 54 publications

(36 citation statements)

References 41 publications

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“…Amphiphilic block copolymers (BCs) have been widely applied in drug delivery systems since it can self‐assemble into micelles in selective solvents and hydrophobic drug molecules are easily encapsulated into the hydrophobic core . As an important nanoscale drug carrier, polymeric micelles can increase drug solubility, prolong drug circulation in the bloodstream and improve their efficacy in tumor tissues, thus greatly reducing the side effects of conventional drugs . One major topic of interest for polymer researchers is stimuli‐responsive polymers which have been incorporated into BCs architectures.…”

Section: Introductionmentioning

confidence: 99%

Light and pH dual‐sensitive biodegradable polymeric nanoparticles for controlled release of cargos

Xia

Zeng

Ding

et al. 2017

J. Polym. Sci. Part A: Polym. Chem.

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In this article, a light and pH dual‐sensitive block copolymer PEG‐b‐poly(MPC‐Azo/DEA) was facilely prepared for the first time by azide‐alkyne click chemistry between amphiphilic block copolymer bearing pendant alkynyl group poly(ethylene glycol)‐poly(5‐methyl‐5‐propargylxycarbonyl‐1,3‐dioxane‐2‐one) (PEG‐b‐poly(MPC)) and two azide‐containing compounds azobenzene derivative (Azo‐N3) and 2‐azido‐1‐ethyl‐diethylamine (DEA‐N3). Light response of the polymeric nanoparticles benefits from the azobenzene segments and pH responsiveness is attributed to DEA moieties. The prepared copolymer could self‐assemble into spherical micelle particles. The morphological changes of these particles in response to dual stimuli were investigated by UV/vis spectroscopy, dynamic light scattering (DLS), and transmission electron microscopy (TEM). Nile Red (NR) was utilized as probe, and fluorescence spectroscopy was served as an evidence for the enhanced release of cargos from polymeric nanoparticles under combined stimulation. Anticancer drug, DOX was loaded into the nanoparticles and the loaded‐DOX could be released from these nanoparticles under dual stimuli. MTT assays further demonstrated that PEG‐b‐poly(MPC) and PEG‐b‐poly(MPC‐Azo/DEA) were of biocompatibility and low toxicity against HepG2 cells as well as SMCC‐7721 cells. More importantly, the prepared DOX‐loaded nanoparticles exhibited good anticancer ability for the two cells. The synthesized light and pH dual‐sensitive biodegradable polymeric nanoparticles were expected to be platforms for precisely controlled release of encapsulated molecules. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017, 55, 1773–1783

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Section: Introductionmentioning

confidence: 99%

Light and pH dual‐sensitive biodegradable polymeric nanoparticles for controlled release of cargos

Xia

Zeng

Ding

et al. 2017

J. Polym. Sci. Part A: Polym. Chem.

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“…[17][18][19][20][21][22][23][24] In particular, redox and pH dual-responsive DDSs were paid more attention because of the 40 existence of redox potential and pH gradient between the extraand intracellular space. [25][26][27][28][29][30][31][32][33][34] Inside the body, glutathione (GSH), a natural reducing agent for disulfide bonds, was found in the blood plasma at µM levels (approximately ~2 µM), due to rapid enzymatic degradation, whereas a substantially high 45 concentration at mM levels (2-10 mM) was found in the cytoplasm of cancer cells. 35 Beside, the pH at both primary and metastasized tumors is lower (6.5-7.2) than the pH of normal tissues (7.4) and intracellular pH of their endosomes (5.5-6.0) and lysosomes (4.5-5.0) are even more acidic.…”

Section: Introductionmentioning

confidence: 99%

Folate-decorated redox/pH dual-responsive degradable prodrug micelles for tumor triggered targeted drug delivery

2016

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To address the obstacles facing the clinical use of paclitaxel, including poor water solubility, side effects and lack of tumor selectivity, a novel folate-decorated and redox and pH dual-responsive micellar drug delivery system was developed based on folate-poly(ethylene 10 glycol)-b-poly((α-paclitaxel-SS-caprolactone)-co-caprolactone) (e.i, FA-PEG-b-P((PTX-SS-CL)-co-CL) conjugates with thiol and acidcleavable linkages. The paclitaxel (PTX) conjugated amphiphilic block copolymer prodrug was self-assembled in phosphate buffer (pH 7.4, 0.1 M) into nanosized spherical micelles (~ 96.5 nm). In vitro release studies demonstrated that the prodrug micelles are relatively stable at normal physiologic conditions but susceptible to tumor-relevant reductive and acidic conditions which would trigger the release of chemically loaded drugs. Notably, folate-decorated PTX prodrug micelles based on FA-PEG-b-P((PTX-SS-CL)-co-CL) conjugates 15 displayed apparent targetability to folate receptor-overexpressing HeLa cells. MTT assays showed that the therapeutic efficacy of these micelles against HeLa cancer cells (IC 50 = 0.75 µg mL -1 ) was enhanced compared with free PTX (IC 50 = 0.87 µg mL -1 ). These results suggest that FA-PEG-b-P((PTX-SS-CL)-co-CL) conjugates may offer a promising strategy for PTX delivery in the treatment of various tumors, with enhanced efficacy and fewer adverse effects. 20

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“…The CCL micelles had superior stability and drug loading capacity than non‐crosslinked micelles. Most importantly, the CCL micelles containing DOX showed enhanced cytotoxicity in MCF‐7/ADR cells due to pH and redox responsive drug release inside the cancer cells . Zhong and coworkers developed pH‐sensitive and biodegradable poly(ethylene glycol)‐poly(2,4,6‐trimethoxybenzylidene‐pentaerythritol carbonate‐co‐pyridyl disulfide carbonate) [PEG‐P(TMBPEC‐co‐PDSC)] copolymers (Figure 5B) which formed reversibly core‐crosslinked micelles.…”

Section: Nanocarriersmentioning

confidence: 99%

Organic Nanocarriers for Delivery and Targeting of Therapeutic Agents for Cancer Treatment

Peng

Bariwal

Kumar

et al. 2020

Advanced Therapeutics

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Nanocarriers have the capability to deliver a variety of drugs to disease sites. Different biological barriers prevent the successful delivery of nanoformulations to target sites, thereby limiting effective therapeutic response. Although numerous efforts have been made to design novel nanocarriers by incorporating various functionalities to get better therapies, most strategies have failed to translate drug delivery systems to the clinic. Impediments such as the incapability to hold drugs stably in nanocarriers during circulation, non‐specific distribution, and inadequate delivery of therapeutic agents to target sites due to complex tumor microenvironment remain a challenge. Herein, different organic polymer and lipid‐based nanocarriers and their encouraging therapeutic effectiveness to treat cancer are discussed. Recent development in multifunctional and stimuli sensitive nanocarriers is also highlighted. Finally, the challenges and innovative strategies to overcome various obstacles and limitations for their successful translation into the clinic are discussed.

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Preparation of pH and redox dual-sensitive core crosslinked micelles for overcoming drug resistance of DOX

Abstract: When incubating the pH and redox dual-sensitive CCL/SS micelles with MCF-7/ADR cells, they could sufficiently overcome drug resistance to deliver DOX into MCF-7/ADR cells, leading to the apoptosis of tumor cells.

Cited by 54 publications

References 41 publications

Light and pH dual‐sensitive biodegradable polymeric nanoparticles for controlled release of cargos

Light and pH dual‐sensitive biodegradable polymeric nanoparticles for controlled release of cargos

Folate-decorated redox/pH dual-responsive degradable prodrug micelles for tumor triggered targeted drug delivery

Organic Nanocarriers for Delivery and Targeting of Therapeutic Agents for Cancer Treatment

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