Polymer–Liposome Complexes with a Functional Hydrogen-Bond Cross-Linker for Preventing Protein Adsorption and Improving Tumor Accumulation

Chiang, Yen-Ting; Cheng, Yung Ting; Lu, Chih Yang; Yen, Yu Wei; Lu, Yu; Yu, Kun; Lyu, Sih Ying; Yang, Chieh Yu; Lo, Chun Liang

doi:10.1021/cm402614k

Cited by 36 publications

(31 citation statements)

References 41 publications

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“…The copolymer mPEG- b -P(MAAc) 40 -chol was synthesized by free radical polymerization using the macroinitiator methoxy poly(ethylene glycol) modified with 4,4′-azobis-(4-cyanopetanoic acid) (mPEG 2 -ABCPA), as previously reported [ 21 ]. The macroinitiator mPEG 2 -ABCPA, transfer reagent 2-amino-ethabethiol hydrochloride (AET-HCl), and monomer methacrylic acid (MAAc) were dissolved in ethanol, and polymerization was initiated at 70 °C.…”

Section: Resultsmentioning

confidence: 99%

“…Among all tested systems, the pH-responsive polymer–liposomal system was considered to represent a promising approach because tumor tissues and endosomes or lysosomes during endocytosis were found to be slightly more acidic than the physiological conditions [ 13 , 14 , 15 ]. Several attempts have been reported [ 10 , 11 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 ]; notably, these mainly employed carboxylated polymers [ 11 , 13 , 18 , 19 , 20 , 24 , 26 , 27 ]. The carboxylated polymers were maintained in an anionic state at physiological conditions, but were protonated at lower pH values, leading to the hydrophobicity of the polymer–liposomes [ 11 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

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Preparation and Characterization of Electrostatically Crosslinked Polymer–Liposomes in Anticancer Therapy

Chiang

Lyu

Wen

et al. 2018

IJMS

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pH-sensitive polymer–liposomes can rapidly release their payloads. However, it is difficult to simultaneously achieve stability and pH-responsiveness in the polymer–liposomes. In this study, stable and pH-sensitive crosslinked polymer–liposomes were fabricated through electrostatic interactions. The pH-sensitive copolymer methoxy poly(ethylene glycol)-block-poly(methacrylic acid)-cholesterol (mPEG-b-P(MAAc)-chol) and crosslinking reagent poly(ethylene glycol) with end-capped with lysine (PEG-Lys2) were synthesized and characterized. At physiological conditions, the pH-sensitive copolymers were anionic and interacted electrostatically with the cationic crosslinker PEG-Lys2, forming the electrostatically-crosslinked polymer–liposomes and stabilizing the liposomal structure. At pH 5.0, the carboxylic groups in mPEG-b-P(MAAc)-chol were neutralized, and the liposomal structure was destroyed. The particle size of the crosslinked polymer–liposomes was approximately 140 nm and the polymer–liposomes were loaded with the anticancer drug doxorubicin. At pH 7.4, the crosslinked polymer–liposomes exhibited good stability with steady particle size and low drug leakage, even in the presence of fetal bovine serum. At pH 5.0, the architecture of the crosslinked polymer–liposomes was damaged following rapid drug release, as observed by using transmission electron microscopy and their apparent size variation. The crosslinked polymer–liposomes were pH-sensitive within the endosome and in the human breast cancer cells MDA-MB-231, as determined by using confocal laser scanning microscopy. The intracellular drug release profiles indicated cytotoxicity in cancer cells. These results indicated that the highly-stable and pH-sensitive electrostatically-crosslinked polymer–liposomes offered a potent drug-delivery system for use in anticancer therapies.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Preparation and Characterization of Electrostatically Crosslinked Polymer–Liposomes in Anticancer Therapy

Chiang

Lyu

Wen

et al. 2018

IJMS

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“…As the cells attached onto the plate, the Fluorescein-loaded polymeric mixed micelles were treated with the A549 cells at 37 • C with 5% CO 2 supply. After 1 and 3 h incubation [52], the excess Fluorescein-loaded polymeric mixed micelles were removed and the cells were washed with phosphate buffering saline (PBS) twice. The cells were thereafter collected using centrifugation.…”

Section: Internalization and Intracellular Drug Releasing Observationmentioning

confidence: 99%

A Novel pH-Tunable Secondary Conformation Containing Mixed Micellar System in Anticancer Treatment

Shih

Jiang

Lin

et al. 2020

Cancers

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In this study, for the first time, we precisely assembled the poly-γ-benzyl-l-glutamate and an amphiphilic copolymer d-α-tocopherol polyethylene glycol succinate into a mixed micellar system for the embedment of the anticancer drug doxorubicin. Importantly, the intracellular drug-releasing behaviors could be controlled by changing the secondary structures of poly-γ-benzyl-l-glutamate via the precise regulation of the buffer’s pH value. Under neutral conditions, the micellar architectures were stabilized by both α-helix secondary structures and the microcrystalline structures. Under acidic conditions (pH 4.0), the interior structures transformed into a coil state with a disordered alignment, inducing the release of the loaded drug. A remarkable cytotoxicity of the Dox-loaded mixed micelles was exhibited toward human lung cancer cells in vitro. The internalizing capability into the cancer cells, as well as the intracellular drug-releasing behaviors, were also identified and observed. The secondary structures containing Dox-loaded mixed micelles had an outstanding antitumor efficacy in human lung cancer A549 cells-bearing nude mice, while little toxicities occurred or interfered with the hepatic or renal functions after the treatments. Thus, these pH-tunable α-helix-containing mixed micelles are innovative and promising for controlled intracellular anticancer drug delivery.

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“…Polymer-drug partners with specific acid-base interactions between hydrophobic drug molecules (R 1 -COOH) and polymer segments (NH 2 -R 2 ) improved the drug loading capacity [110]. Hydrogen bonding formation between the guest drug and the host polymer has also been explored [111][112][113][114][115][116].…”

Section: Covalent and Non-covalent Dendrimer-drug Systemsmentioning

confidence: 99%

Polyester Dendrimers: Smart Carriers for Drug Delivery

Twibanire

Grindley

2014

Polymers

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Polyester dendrimers have been shown to be outstanding candidates for biomedical applications. Compared to traditional polymeric drug vehicles, these biodegradable dendrimers show excellent advantages especially as drug delivery systems because they are non-toxic. Here, advances on polyester dendrimers as smart carriers for drug delivery applications have been surveyed. Both covalent and non-covalent incorporation of drugs are discussed.

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Polymer–Liposome Complexes with a Functional Hydrogen-Bond Cross-Linker for Preventing Protein Adsorption and Improving Tumor Accumulation

Cited by 36 publications

References 41 publications

Preparation and Characterization of Electrostatically Crosslinked Polymer–Liposomes in Anticancer Therapy

Preparation and Characterization of Electrostatically Crosslinked Polymer–Liposomes in Anticancer Therapy

A Novel pH-Tunable Secondary Conformation Containing Mixed Micellar System in Anticancer Treatment

Polyester Dendrimers: Smart Carriers for Drug Delivery

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