Self-assembled polymeric micelles for targeted photodynamic therapy of human epidermal growth factor receptor 2 overexpressing breast cancer
Self-assembled polymeric micelles for targeted photodynamic therapy of human epidermal growth factor receptor 2 overexpressing breast cancer
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DOI：
10.1088/1361-6528/abf2fe
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发表时间：
2021-07-02
期刊：
影响因子：
3.5
通讯作者：
Kim, Ye-Ji
中科院分区：
文献类型：
--
作者：
Kim, Young-Jin;Ha, Ji-Hui;Kim, Ye-Ji
光动力疗法(PDT)是治疗多种恶性肿瘤的一种很有前途的替代治疗方法。然而，PDT系统通常涉及不理想的肿瘤特异性和光敏剂在靶细胞周围的非特异性积聚，导致对邻近健康正常细胞的光毒性损伤。在本研究中，我们通过自组装方法制备了脱镁叶绿酸a(Pheo A)/人表皮生长因子受体2(HER2)靶向多肽(表位形式，HLTV，PEG2-LTVSPWY)-共偶联甲氧基聚乙二醇-嵌段-聚(L-赖氨酸盐酸盐)/透明质酸(P3H2)聚合物胶束，用于HER2靶向PDT治疗乳腺癌，从而提高了PDT的疗效。合成的P3H2聚合物胶束呈球形，在水溶液中的平均粒径为125.7+/-21.2nm.体外细胞毒性实验结果表明，P3H2聚合物胶束由于靶向性增强，显著提高了对SK-BR-3细胞的PDT效率。此外，使用P3H2聚合物胶束的PDT治疗通过诱导更高的细胞内活性氧生成和细胞凋亡而有效地杀死乳腺癌细胞。特别是，三维细胞培养模型证明了P3H2聚合物胶束对SK-BR-3细胞的协同PDT效果。基于这些结果，使用P3H2聚合物胶束的PDT治疗可以作为一种高效的乳腺癌治疗方式。
Photodynamic therapy (PDT) has been extensively explored as a promising alternative therapeutic approach for many malignant tumors. However, the PDT system generally involves unsatisfactory tumor specificity and nonspecific accumulation of photosensitizers around the target cancer cells, leading to phototoxic damage to adjacent healthy normal cells. In this study, we developed pheophorbide a (Pheo a)/human epidermal growth factor receptor 2 (HER2) targeting peptide (epitope form, HLTV, PEG2-LTVSPWY)-co-conjugated methoxy poly(ethylene glycol)-block-poly(L-lysine hydrochloride) (PEG-PLL)/hyaluronic acid (HA) (P3H2) polymeric micelles via a self-assembly method for HER2-targeted PDT treatment for breast cancer, thereby enhancing the PDT efficacy. The synthesized P3H2 polymeric micelles were spherical, with an average diameter of 125.7 +/- 21.2 nm in an aqueous solution. The results of in vitro cytotoxicity assays demonstrated that the P3H2 polymeric micelles significantly improved PDT efficacy on the SK-BR-3 cells due to the enhanced targeting ability. In addition, PDT treatment using the P3H2 polymeric micelles effectively killed breast cancer cells by inducing higher intracellular reactive oxygen species generation and apoptotic cell death. In particular, the three-dimensional cell culture model proved the synergistic PDT efficacy using P3H2 polymeric micelles on the SK-BR-3 cells. Based on these results, the PDT treatment using P3H2 polymeric micelles can serve as a highly effective therapeutic modality for breast cancer.