Wang Junxia, Shen Song, Li Jie, Cao Ziyang, Yang Xianzhu
Guangzhou First People's Hospital, School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou 511442, People's Republic of China.
National Engineering Research Center for Tissue Restoration and Reconstruction, and Key Laboratory of Biomedical Engineering of Guangdong Province, South China University of Technology, Guangzhou, Guangdong 510006, People's Republic of China.
ACS Nano. 2021 Mar 23;15(3):4636-4646. doi: 10.1021/acsnano.0c08996. Epub 2021 Mar 2.
Simultaneously targeting tumor cells and nonmalignant cells represent a more efficient strategy for replacing the traditional method of targeting only tumor cells, and co-delivery nanocarriers have inherent advantages to achieve this goal. However, differential delivery of multiple agents to various types of cell with different spatial distribution patterns remains a large challenge. Herein, we developed a nanocarrier of platinum(IV) prodrug and BLZ-945, BLZ@S-NP/Pt, to differentially target tumor cells and tumor-associated macrophages (TAMs). The BLZ@S-NP/Pt undergoes shrinkage to small platinum(IV) prodrug-conjugating nanoparticles under 660 nm light, resulting in deep tumor penetration to kill more cancer cells. Meanwhile, such shrinkage also enables the rapid release of BLZ-945 in the perivascular regions of tumor to preferentially deplete TAMs (enriched in perivascular regions). Therefore, BLZ@S-NP/Pt differentially and precisely delivers agents to TAMs and tumor cells located in different spatial distribution, respectively, eventually having synergistic anticancer effects in multiple tumor models.
同时靶向肿瘤细胞和非恶性细胞是一种比仅靶向肿瘤细胞的传统方法更有效的策略，而共递送纳米载体具有实现这一目标的固有优势。然而，将多种药物以不同的空间分布模式差异递送至各种类型的细胞仍然是一个巨大的挑战。在此，我们开发了一种铂（IV）前药和BLZ-945的纳米载体，即BLZ@S-NP/Pt，以差异靶向肿瘤细胞和肿瘤相关巨噬细胞（TAM）。BLZ@S-NP/Pt在660nm光下收缩为小的铂（IV）前药共轭纳米颗粒，从而实现肿瘤深部渗透以杀死更多癌细胞。同时，这种收缩还能使BLZ-945在肿瘤血管周围区域快速释放，优先消耗（富集于血管周围区域的）TAM。因此，BLZ@S-NP/Pt分别将药物差异且精确地递送至位于不同空间分布的TAM和肿瘤细胞，最终在多种肿瘤模型中产生协同抗癌作用。
