Sui Dezhi, Li Changzhi, Tang Xueying, Meng Xianmin, Ding Junqiang, Yang Qiongfen, Qi Zhaowei, Liu Xinrong, Deng Yihui, Song Yanzhi
College of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
Acta Pharm Sin B. 2023 Jan;13(1):425-439. doi: 10.1016/j.apsb.2022.06.005. Epub 2022 Jun 11.
Immunoscenescence plays a key role in the initiation and development of tumors. Furthermore, immunoscenescence also impacts drug delivery and cancer therapeutic efficacy. To reduce the impact of immunosenescence on anti-tumor therapy, this experimental plan aimed to use neutrophils with tumor tropism properties to deliver sialic acid (SA)-modified liposomes into the tumor, kill tumor cells SA-mediated photochemotherapy, enhance infiltration of neutrophils into the tumor, induce immunogenic death of tumor cells with chemotherapy, enhance infiltration of CD8 T cells into the tumor-draining lymph nodes and tumors of immunosenescent mice, and achieve SA-mediated photochemotherapy. We found that CD8 T cell and neutrophil levels in 16-month-old mice were significantly lower than those in 2- and 8-month-old mice; 16-month-old mice exhibited immunosenescence. The anti-tumor efficacy of SA-mediated non-photochemotherapy declined in 16-month-old mice, and tumors recurred after scabbing. SA-mediated photochemotherapy enhanced tumor infiltration by CD8 T cells and neutrophils, induced crusting and regression of tumors in 8-month-old mice, inhibited metastasis and recurrence of tumors and eliminated the immunosenescence-induced decline in antitumor therapeutic efficacy in 16-month-old mice the light-heat-chemical-immunity conversion.
免疫衰老在肿瘤的发生和发展中起关键作用。此外，免疫衰老还影响药物递送和癌症治疗效果。为了降低免疫衰老对抗肿瘤治疗的影响，本实验方案旨在利用具有肿瘤嗜性特性的中性粒细胞将唾液酸（SA）修饰的脂质体递送至肿瘤中，通过SA介导的光化学疗法杀死肿瘤细胞，增强中性粒细胞向肿瘤内的浸润，通过化疗诱导肿瘤细胞发生免疫原性死亡，增强CD8 T细胞向免疫衰老小鼠肿瘤引流淋巴结和肿瘤内的浸润，并实现SA介导的光化学疗法。我们发现，16月龄小鼠的CD8 T细胞和中性粒细胞水平显著低于2月龄和8月龄小鼠；16月龄小鼠表现出免疫衰老。SA介导的非光化学疗法在16月龄小鼠中的抗肿瘤效果下降，结痂后肿瘤复发。SA介导的光化学疗法增强了CD8 T细胞和中性粒细胞对肿瘤的浸润，在8月龄小鼠中诱导肿瘤结痂和消退，抑制肿瘤转移和复发，并消除了免疫衰老引起的16月龄小鼠抗肿瘤治疗效果下降——光-热-化学-免疫转换。
