科研之友
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摘要
Poor tumor selectivity and short life span of reactive oxygen species (ROS) are two major challenges in photodynamic therapy (PDT). In this study, a selftransformable pH-driven membrane anchoring photosensitizer (pHMAPS) is used to realize tumor-specific accumulation and in situ PDT on tumor cell membrane to maximize the therapeutic potency. It is found that pHMAPS was able to form alpha-helix structure under acidic condition (pH 6.5 or 5.5), while remain random coil at normal pH of 7.4. This pH-driven secondary structure switch enables the successful insertion of pHMAPS into membrane lipid bilayer, especially for cancerous cell membrane in the acidic tumor microenvironment. Under laser irradiation, cytotoxic ROS is generated in the immediate vicinity of cell membrane, resulting in superior cell killing effect in vitro and significant inhibition of tumor growth in vivo. Importantly, benefited from this membrane-specific PDT, tumor growth-induced hepatic, pulmonary, as well as osseous metastases of breast cancer cells are also retarded after PDT treatment. Thus, the membrane localized PDT by pHMAPS provides a simple but effective strategy to enhance the medical performance of photosensitizing agents in cancer therapy.
- 出版日期2017-9-26
- 单位武汉大学
