期刊
JOURNAL OF BIOMEDICAL NANOTECHNOLOGY
卷 15, 期 9, 页码 1897-1908出版社
AMER SCIENTIFIC PUBLISHERS
DOI: 10.1166/jbn.2019.2833
关键词
Enzyme-Responsive Copolymer; Polymer Produg; Theranostic; Nanomedicines; Anticancer
资金
- National Natural Science Foundation of China [51673127, 51873120, 81621003, 81801117]
- National Science and Technology Major Project [2017ZX09304023]
- Post-Doctor Research Project, West China Hospital, Sichuan University [2018HXBH055]
- Department of Science and Technology of Sichuan Province [2018HH0006]
- Ministry of Science and Technology of the People's Republic of China [2015DFE52780]
With the advance in nanomedicine, diagnostic and therapeutic nanoscale prodrugs have been rapidly developed in the field of cancer treatment. In this study, we constructed an enzyme-responsive polymer-paclitaxel (PTX) prodrug with a biocompatible saccharide-containing polymer backbone through the reversible addition-fragmentation chain transfer (RAFT) polymerization. A near-infrared fluorescent molecule (pheophorbide a) and magnetic resonance imaging (MRI) contrast agent (gadolinium-tetraazacyclododecanetetraacetic acid) were further conjugated onto the copolymer backbone to impart the ability of multimode imaging and tracing, forming the final diagnosis and treatment polymeric prodrug. This prodrug was amphiphilic and was able to self-assemble into uniform-size nanoparticles (80.1 nm). With the specific catalysis of enzymes, the anti-cancer drug, PTX, in the nanoparticles could be effectively released to kill cancer cells. The results of near-infrared fluorescence imaging and MRI showed that the diagnostic prodrug was preferentially concentrated at the tumor site compared with the free imaging reagents, suggesting improved and durable tumor imaging effects, which are beneficial for precise cancer diagnosis. The tumor growth in the mice could be effectively retarded after the administration of the prodrug. The tumor almost completely disappeared till the final treatment, and the tumor inhibition rate was as high as 96.4%. Immunohistochemical analysis indicated that the high anti-tumor effects might be attributed to the result that the prodrug not only induced the apoptosis of tumor cells, but also inhibited the formation of new blood vessels in the tumor environment. Therefore, this theranostic prodrug, which is based on the saccharide-containing polymer, holds potency for the development of a robust nanoscale platform for the diagnosis and treatment of cancer.
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