期刊
JOURNAL OF MATERIALS CHEMISTRY B
卷 7, 期 4, 页码 651-664出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/c8tb02882f
关键词
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资金
- National Natural Science Foundation of China [51773231]
- National Natural Science Foundation of Guangdong Province [2016A030313315, 2014A030312018]
- Tip-top Scientific and Technical Innovative Youth Talents of Guangdong special support program [2014TQ01R651]
- Project of Key Laboratory of Sensing Technology and Biomedical Instruments of Guangdong Province [2011A060901013]
- Yale University
Novel multifunctional drug nanocarriers have been successfully fabricated from a new type of enzymatically synthesized, biodegradable block copolymer, PEG-poly(-pentadecalactone-co-N-methyldiethyleneamine-co-3,3-thiodipropionate) (PEG-PPMT), which was responsive to tumor-relevant acidic pH (5.0-6.5) and intracellular reactive oxygen species (ROS) of tumor cells. The PEG-PPMT copolymers could self-assemble to form nano-scaled particles in aqueous solutions, which are stable in physiological solutions, but swell substantially upon reducing the pH from 7.4 to 5.0 and/or in the presence of ROS on account of the protonation of the tertiary amino groups and oxidation of the thioether groups, causing a hydrophobic to hydrophilic transition in the nanoparticle cores. Consistently, docetaxel (DTX) encapsulated in PEG-PPMT nanoparticles can be triggered in a synergistic manner by acidic pH and a high-ROS environment in tumor cells to release the hydrophobic drug at accelerated rates for efficient tumor growth inhibition. In particular, DTX encapsulated in PEG-PPMT-11% PDL and PEG-PPMT-28% PDL nanoparticles exhibit extraordinarily enhanced potency (95% and 93% tumor-inhibiting efficiency, respectively) in inhibiting the growth of ROS-rich CT-26 tumors xenografted in mice. Importantly, biosafety analyses show minimal toxicity of DTX-loaded PEG-PPMT nanoparticles toward normal organs including liver and kidneys during the in vivo antitumor treatments. These results demonstrate that the PEG-PPMT nanoparticles are promising pH and ROS dual-responsive multifunctional nanocarriers for tumor site specific, controlled release of anticancer drugs to treat ROS-rich tumors.
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