期刊
BIOACTIVE MATERIALS
卷 6, 期 9, 页码 2894-2904出版社
KEAI PUBLISHING LTD
DOI: 10.1016/j.bioactmat.2021.02.011
关键词
Cylindrical polymer brushes; Unimolecular micelles; Prodrug; Reduction-responsive; Cancer therapy
资金
- National Natural Science Foundation of China [51703187, 31671037]
- Basic and Frontier Research Project of Chongqing [cstc2018jcyjAX0104]
By synthesizing cylindrical polymer brushes of different lengths, research on their delivery performance in cancer therapy was conducted. The shorter CPBs were found to have higher drug release efficiency and better anti-tumor effects.
Polymer systems can be designed into different structures and morphologies according to their physical and chemical performance requirements, and are considered as one of the most promising controlled delivery systems that can effectively improve the cancer therapeutic index. However, the majority of the polymer delivery systems are designed to be simple spherical nanostructures. To explore morphology/size-oriented delivery performance optimization, here, we synthesized three novel cylindrical polymer brushes (CPBs) by atom transfer radical polymerization (ATRP), which were cellulose-g-(CPT-b-OEGMA) (CCO) with different lengths (similar to 86, similar to 40, and similar to 21 nm). The CPBs are composed of bio-degradable cellulose as the carrier, poly(ethylene glycol) methyl ether methacrylate (OEGMA) as hydrophily block, and glutathione (GSH)-responsive hydrophobic camptothecin (CPT) monomer as loaded anticancer drug. By controlling the chain length of the initiator, three kinds of polymeric prodrugs with different lengths (CCO-1, CCO-2, and CCO-3) could be self-organized into unimolecular micelles in water. We carried out comparative studies of three polymers, whose results verified that the shorter CPBs exhibited higher drug release efficiency, more cellular uptake, and enhanced tumor permeability, accompanied by shortened blood circulation time and lower tumor accumulation. As evidenced by in vivo experiments, the shorter CPBs exhibited higher anti-tumor efficiency, revealing that the size advantage has a higher priority than the anisotropic structure advantage. This provided vital information as to design an anisotropic polymer-based drug delivery system for cancer therapy.
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