School of Biomedical Sciences and Engineering, Guangzhou International Campus, South China University of Technology, Guangzhou, 510006, P. R. China.
National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou, 510006, P. R. China.
Adv Mater. 2022 Feb;34(8):e2106654. doi: 10.1002/adma.202106654. Epub 2022 Jan 13.
Cancer nanomedicine combined with immunotherapy has become a promising strategy for treating cancer in terms of safety and potency; however, precise regulation of the activation of antitumor immunity remains challenging. Herein, a smart semiconducting polymer nano-immunomodulator (SPNI), which responds to the acidic tumor microenvironment (TME), for precision photodynamic immunotherapy of cancer, is reported. The SPNI is self-assembled by a near-infrared (NIR)-absorbing semiconducting polymer and an amphipathic polymer conjugated with a Toll-like receptor 7 (TLR7) agonist via an acid-labile linker. Upon arrival at tumor site, SPNI undergoes hydrolysis and triggers an efficient liberation of TLR7 agonist in response to the acidic TME for dendritic cell activation. Moreover, SPNI exerts photodynamic effects for direct tumor eradication and immunogenic cancer cell death under NIR photoirradiation. The synergistic action of released immunogenic factors and acidic-TME-activated TLR7 agonist can serve as an in situ generated cancer vaccine to evoke strong antitumor activities. Notably, such localized immune activation boosts systemic antitumor immune responses, resulting in enhanced cytotoxic CD8 T infiltration to inhibit tumor growth and metastasis. Thereby, this work presents a general strategy to devise prodrug of immunotherapeutics for precise regulation of cancer immunotherapy.
癌症纳米医学与免疫疗法相结合，在安全性和功效方面已成为治疗癌症的一种有前途的策略；然而，精确调控抗肿瘤免疫仍然具有挑战性。在此，报道了一种智能半导体聚合物纳米免疫调节剂（SPNI），该调节剂可响应酸性肿瘤微环境（TME），用于癌症的精准光动力免疫治疗。SPNI 由近红外（NIR）吸收半导体聚合物和通过酸不稳定键连接 TLR7 激动剂的两亲聚合物自组装而成。到达肿瘤部位后，SPNI 发生水解，并响应酸性 TME 高效释放 TLR7 激动剂以激活树突状细胞。此外，SPNI 在近红外光照射下发挥光动力效应，直接消除肿瘤并诱导免疫原性癌细胞死亡。释放的免疫原性因子和酸性 TME 激活的 TLR7 激动剂的协同作用可用作原位生成的癌症疫苗，以引发强烈的抗肿瘤活性。值得注意的是，这种局部免疫激活增强了全身抗肿瘤免疫反应，导致细胞毒性 CD8 T 细胞浸润增强，从而抑制肿瘤生长和转移。因此，这项工作提出了一种用于精确调控癌症免疫治疗的免疫治疗药物前药设计的通用策略。
