A Self-Transformable pH-Driven Membrane-Anchoring Photosensitizer for Effective Photodynamic Therapy to Inhibit Tumor Growth and Metastasis
A Self-Transformable pH-Driven Membrane-Anchoring Photosensitizer for Effective Photodynamic Therapy to Inhibit Tumor Growth and Metastasis
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一种自转化 pH 驱动膜锚定光敏剂，用于有效光动力疗法抑制肿瘤生长和转移
DOI：
10.1002/adfm.201702122
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发表时间：
2017-09-26
影响因子：
19
通讯作者：
Zhang, Xian-Zheng
中科院分区：
文献类型：
--
作者：
Luo, Guo-Feng;Chen, Wei-Hai;Zhang, Xian-Zheng
肿瘤选择性差和活性氧寿命短是光动力学治疗（PDT）的两个主要挑战。本研究利用一种可自转换的pH驱动的膜锚定光敏剂（pHMAPS）实现肿瘤特异性聚集，并在肿瘤细胞膜上进行原位PDT，以最大限度地发挥其治疗效能。结果表明，pHMAPS在酸性条件（pH 6.5或5.5）下能形成α-螺旋结构，而在正常pH 7.4下仍保持无规卷曲。这种pH驱动的二级结构开关使得pHMAPS能够成功插入膜脂质双层，特别是对于酸性肿瘤微环境中的癌细胞膜。在激光照射下，细胞膜附近产生细胞毒性活性氧，在体外具有上级细胞杀伤作用，在体内对肿瘤生长有显着抑制作用。重要的是，受益于这种膜特异性PDT，PDT治疗后肿瘤生长诱导的乳腺癌细胞的肝、肺以及骨转移也被延缓。因此，通过pHMAPS的膜定位PDT提供了一种简单但有效的策略，以提高光敏剂在癌症治疗中的医疗性能。
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.