Combination of tumor vessel normalization and immune checkpoint blockade for breast cancer treatment via multifunctional nanocomplexes.
Combination of tumor vessel normalization and immune checkpoint blockade for breast cancer treatment via multifunctional nanocomplexes.
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DOI：
10.1039/d2bm00600f
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发表时间：
2022-06
影响因子：
6.6
通讯作者：
Yingping Zeng;Tong Yu;Shufeng Zhang;Guang-Chen Song;Tingting Meng;Hong Yuan;F. Hu
中科院分区：
文献类型：
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作者：
Yingping Zeng;Tong Yu;Shufeng Zhang;Guang-Chen Song;Tingting Meng;Hong Yuan;F. Hu
肿瘤血管正常化可以缓解缺氧，减少免疫抑制细胞的瘤内浸润，增加免疫效应细胞（CD8+T细胞）的瘤内浸润，进一步逆转免疫抑制微环境。在此，制备了纳米复合物（lipo/St@FA-COSA/BMS-202），它可以将药物准确地递送至肿瘤组织，并在不同部位以不同速率释放不同的药物，将肿瘤血管正常化与免疫检查点阻断结合起来。体外药物释放结果显示，在pH 6.5的释放介质中，lipo/St@FA-COSA/BMS-202快速释放血管正常化药物（舒尼替尼，St）并缓慢释放PD-1/PD-L1阻断药物（BMS-202）。体内实验结果表明，快速释放的St使肿瘤血管正常化并形成免疫支持微环境，从而提高了BMS-202的抗肿瘤功效。总之，该药物递送策略显着抑制肿瘤生长，具有优异的抗肿瘤功效，可为有效的肿瘤治疗提供潜在的方法。
Tumor vessel normalization can alleviate hypoxia, reduce the intratumoral infiltration of immunosuppressive cells and increase the intratumoral infiltration of immune effector cells (CD8+ T cells), further reversing the immunosuppressive microenvironment. Here, nanocomplexes (lipo/St@FA-COSA/BMS-202) which can accurately deliver drugs to tumor tissues and release different drugs at different sites with different rates were prepared to combine tumor vessel normalization with immune checkpoint blockade. The results of drug release in vitro showed that in a pH 6.5 release medium, lipo/St@FA-COSA/BMS-202 rapidly released the vascular normalizing drug (sunitinib, St) and slowly released the PD-1/PD-L1-blocking drug (BMS-202). The results of in vivo experiments showed that the rapidly released St normalized tumor vessels and formed an immunosupportive microenvironment which improved the anti-tumor efficacy of BMS-202. In conclusion, the drug delivery strategy significantly inhibited tumor growth and had excellent anti-tumor efficacy, which can provide a potential approach for effective tumor treatment.