Sialic acid-mediated photochemotherapy enhances infiltration of CD8^(+)T cells from tumor-draining lymph nodes into tumors of immunosenescent mice  

作　　者：Dezhi Sui Changzhi Li Xueying Tang Xianmin Meng Junqiang Ding Qiongfen Yang Zhaowei Qi Xinrong Liu Yihui Deng Yanzhi Song 

机构地区：[1]College of Pharmacy,Shenyang Pharmaceutical University,Shenyang 110016,China

出　　处：《Acta Pharmaceutica Sinica B》2023年第1期425-439,共15页药学学报（英文版）

基　　金：supported by the National Natural Science Foundation of China(Grant Nos.81973271,81703456,and 81573375);the Career Development Plan for Young and Middle-aged Teachers of Shenyang Pharmaceutical University(ZQN2021009,China)。

摘　　要：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 via 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 tumordraining 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 via the light-heat-chemical-immunity conversion.

关 键 词：IMMUNOSENESCENCE Sialic acid PHOTOCHEMOTHERAPY CD8^(+)T cells DOXORUBICIN NEUTROPHILS Indocyanine green Liposomes 

分 类 号：R730.5[医药卫生—肿瘤]