Guangdong Key Laboratory of Nanomedicine, CAS Key Lab for Health Informatics, Institute of Biomedicine and Biotechnology , Shenzhen Institutes of Advanced Technology (SIAT), Chinese Academy of Sciences , Shenzhen 518055 , People's Republic of China.
University of Chinese Academy of Sciences , Beijing 100049 , People's Republic of China.
Biomacromolecules. 2018 Jun 11;19(6):2146-2155. doi: 10.1021/acs.biomac.8b00239. Epub 2018 Apr 24.
One approach to cancer immunotherapy is the repolarization of immunosuppressive tumor-associated macrophages (TAMs) to antitumor M1 macrophages. The present study developed galactose-functionalized zinc protoporphyrin IX (ZnPP) grafted poly(l-lysine)- b-poly(ethylene glycol) polypeptide micelles (ZnPP PM) for TAM-targeted immunopotentiator delivery, which aimed at in vivo repolarization of TAMs to antitumor M1 macrophages. The outcomes revealed that ROS-inducing ZnPP PM demonstrated specificity for the in vitro and in vivo targeting of macrophages, elevated the level of ROS, and lowered STAT3 expression in BM-TAMs. Poly I:C (PIC, a TLR3 agonist)-loaded ZnPP PM (ZnPP PM/PIC) efficiently repolarized TAMs to M1 macrophages, which were reliant on ROS generation. Further, ZnPP PM/PIC substantially elevated the activated NK cells and T lymphocytes in B16-F10 melanoma tumors, which caused vigorous tumor regression. Therefore, the TAM-targeted transport of an immunologic adjuvant with ZnPP-grafted nanovectors may be a potential strategy to repolarize TAMs to M1 macrophages in situ for effective cancer immunotherapy.
一种癌症免疫疗法是将免疫抑制性肿瘤相关巨噬细胞（TAMs）重极化为抗肿瘤 M1 巨噬细胞。本研究开发了半乳糖功能化锌原卟啉 IX（ZnPP）接枝聚（L-赖氨酸）-b-聚（乙二醇）多肽胶束（ZnPP PM）用于 TAM 靶向免疫增强剂递送，旨在体内将 TAMs 重极化为抗肿瘤 M1 巨噬细胞。结果表明，ROS 诱导的 ZnPP PM 表现出对体外和体内巨噬细胞的特异性靶向作用，增加了 ROS 水平，并降低了 BM-TAMs 中的 STAT3 表达。负载聚肌苷酸：聚胞苷酸（PIC，TLR3 激动剂）的 ZnPP PM（ZnPP PM/PIC）有效地将 TAMs 重极化为 M1 巨噬细胞，这依赖于 ROS 的产生。此外，ZnPP PM/PIC 显著增加了 B16-F10 黑色素瘤肿瘤中的活化 NK 细胞和 T 淋巴细胞，导致强烈的肿瘤消退。因此，用 ZnPP 接枝纳米载体进行 TAM 靶向免疫佐剂输送可能是一种将 TAMs 原位重极化为 M1 巨噬细胞以进行有效癌症免疫治疗的潜在策略。
