期刊
JOURNAL OF CONTROLLED RELEASE
卷 339, 期 -, 页码 130-142出版社
ELSEVIER
DOI: 10.1016/j.jconrel.2021.09.023
关键词
Photodynamic-chemotherapy; Hypoxia-responsive; Drug delivery; Polyprodrug; Polymeric micelle
资金
- Na-tional Natural Science Foundation of China (NNSFC) Project [21875234]
- National Key Research and Development Program of China [2020YFA0710700]
The study highlights the important influence of the inherent hypoxic microenvironment of solid tumors on tumor growth and spread. By preparing a polyprodrug, a complementary photodynamic-chemotherapy strategy can be achieved, effectively suppressing tumor growth through a combination of photodynamic therapy and chemotherapy.
The inherent hypoxic microenvironment of solid tumors has an important influence on tumor growth, distant metastasis, and invasiveness. The heterogeneous distribution of hypoxic regions inside tumors limits the therapeutic efficacy of O-2-assisted therapeutic strategy (e.g. photodynamic therapy (PDT)). On the other hand, the hypoxia-activable prodrugs cannot work effectively in the regions with enough O-2 concentration. To address the issues, we prepare a block copolymer polyprodrug consisting of polyethylene glycol (PEG) and copolymerized segments of nitroimidazole-linked camptothecin (CPT) methacrylate and 5,10,15,20-tetraphenylporphyrin (TPP)-containing methacrylate monomers for complementary photodynamic-chemotherapy. The polyprodrug can self-assemble into polymeric micelles in aqueous solution with suitable size and high stability. After intravenous injection, the polyprodrug micelles show tumor accumulation. Followed by light irradiation (650 nm) at tumor sites, TPP moieties induce singlet oxygen (O-1(2)) production in the oxygen-rich area to exert PDT and cause transformation of the oxygen-rich areas into hypoxia. Simultaneously, in the hypoxic areas, the hypoxia-responsive polyprodrugs can be activated to release free CPT due to the cleavage of nitroimidazole linkages. The polyprodrug micelles with the segments for PDT and hypoxia-activable CPT efficiently suppress the growth of HeLa tumors. The well-defined polyprodrug amphiphiles offer an effective strategy to overcome the disadvantages of single treatment of PDT or hypoxia-responsive prodrugs for complementary photodynamic-chemotherapy of cancers.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据