Department of Biomedical Engineering, College of Future Technology, National Biomedical Imaging Center, Peking University, Beijing, 100871, China.
Princess Margaret Cancer Centre, University Health Network, 101 College Street, PMCRT 5-354, Toronto, Ontario, M5G 1L7, Canada.
Signal Transduct Target Ther. 2022 Feb 28;7(1):64. doi: 10.1038/s41392-022-00906-2.
Targeted photodynamic therapy (TPDT) is considered superior to conventional photodynamic therapy due to the enhanced uptake of photosensitizers by tumor cells. In this paper, an amphiphilic and asymmetric cyclo-Arg-Gly-Asp-d-Tyr-Lys(cRGDyK)-conjugated silicon phthalocyanine (RSP) was synthesized by covalently attaching the tripeptide Arg-Gly-Asp (RGD) to silicone phthalocyanine in the axial direction for TPDT of triple-negative breast cancer (TNBC). RSP was characterized by spectroscopy as a monomer in physiological buffer. Meanwhile, the modification of RSP with RGD led to a high accumulation of the photosensitizer in TNBC cells overexpressing ανβ3 integrin receptors which can bind RGD, greatly reducing the risk of phototoxicity. In vitro photodynamic experiments showed that the IC50 of RSP was 295.96 nM in the 4T1 cell line, which caused significant apoptosis of the tumor cells. The tumor inhibition rate of RSP on the orthotopic murine TNBC achieved 74%, while the untargeted photosensitizer exhibited no obvious tumor inhibition. Overall, such novel targeted silicon phthalocyanine has good potential for clinical translation due to its simple synthesis route, strong targeting, and high therapeutic efficacy for TPDT treatment of TNBC.
靶向光动力疗法（TPDT）由于肿瘤细胞对光敏剂的摄取增强，被认为优于传统光动力疗法。在本文中，通过在轴向共价连接三肽 Arg-Gly-Asp（RGD），合成了一种两亲性和不对称的环精氨酸-甘氨酸-天冬氨酸-酪氨酰-赖氨酸（cRGDyK）-共轭硅酞菁（RSP），用于三阴性乳腺癌（TNBC）的 TPDT。RSP 在生理缓冲液中通过光谱学鉴定为单体。同时，RSP 与 RGD 的修饰导致在过度表达可结合 RGD 的 ανβ3 整联蛋白受体的 TNBC 细胞中光敏剂的高积累，大大降低了光毒性的风险。体外光动力实验表明，RSP 在 4T1 细胞系中的 IC50 为 295.96 nM，导致肿瘤细胞发生显著凋亡。RSP 对原位小鼠 TNBC 的肿瘤抑制率达到 74%，而无靶向的光敏剂则没有明显的肿瘤抑制作用。总的来说，由于其简单的合成路线、强靶向性和治疗 TNBC 的 TPDT 的高效疗效，这种新型靶向硅酞菁具有很好的临床转化潜力。
