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Self-assembled micelles of PEG–poly(disulfide carbamate amine) copolymers for intracellular dual-responsive drug delivery

Author:
Lin, Chao, Lou, Bo, Zhao, Jie, Jin, Rong, Zhao, Peng, Li, Jianbo, Ren, Jie
Source:
Journal of materials chemistry B 2016 v.4 no.5 pp. 902-909
ISSN:
2050-7518
Subject:
carbonates, composite polymers, condensation reactions, confocal laser scanning microscopy, cytotoxicity, doxorubicin, growth retardation, image analysis, intravenous injection, mice, micelles, nanocarriers, neoplasm cells, neoplasms, piperazine, polyethylene glycol
Abstract:
A group of poly(ethylene glycol)-poly(disulfide carbamate amine) (PEG–SSPCA) diblock copolymers is designed, prepared and successfully applied for intracellular dual-responsive drug delivery. PEG–SSPCA copolymers can be obtained by polycondensation reaction between 2,2′-dithiodiethanol bis(p-nitrophenyl carbonate) and a mixture of amino-terminal PEG (Mw = 5k) and tertiary amine-containing primary diamine. The copolymers self-assemble to form stable nanoscale micelles under physiological conditions and the micelles may undergo rapid destabilization under acidic or reductive conditions. The micelles based on the copolymer having a 1,4-bis(3-aminopropyl)piperazine (BAP) residue (termed as PEG–SSBAP) can carry anti-cancer drugs, doxorubicin (Dox) with the drug loading content of 5.7 ± 1%. The in vitro accumulative drug release test of Dox-loaded PEG–SSBAP micelles manifests slow drug release under physiological conditions and accelerated drug release in an acidic or reductive environment, but sufficient drug release in an acidic plus reductive environment. Confocal laser scanning microscopy imaging indicates that Dox-loaded PEG–SSBAP micelles are capable of delivering and liberating Dox into the cellular nucleus. In vitro, PEG–SSBAP micelles are of low toxicity against different cancer cells at a high concentration of 400 μg mL⁻¹. However, Dox-loaded PEG–SSBAP micelles exert marked cytotoxicity against the cancer cells. In vivo, intravenous administration of the Dox-loaded micelles at a medium Dox dose of 2.5 mg kg⁻¹ induces considerable growth inhibition of HepG2 tumor xenografted in nude mice with anti-cancer efficacy comparable to that of free Dox-chemotherapy but negligible systemic toxicity. The PEG–SSPCA block copolymer represents an efficient nano-carrier for controlled drug release and cancer therapy.
Agid:
6423739