Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Road, Changchun, 130022, China.
Jilin Biomedical Polymers Engineering Laboratory, Changchun Institute of Applied Chemistry, 5625 Renmin Road, Changchun, 130022, China.
Adv Mater. 2021 Feb;33(7):e2007293. doi: 10.1002/adma.202007293. Epub 2021 Jan 14.
Using nanotechnology for improving the immunotherapy efficiency represents a major research interest in recent years. However, there are paradoxes and obstacles in using a single nanoparticle to fulfill all the requirements in the complicated immune activation processes. Herein, a supramolecular assembled programmable immune activation nanomedicine (PIAN) for sequentially finishing multiple steps after intravenous injection and eliciting robust antitumor immunity in situ is reported. The programmable nanomedicine is constructed by supramolecular assembly via host-guest interactions between poly-[(N-2-hydroxyethyl)-aspartamide]-Pt(IV)/β-cyclodextrin (PPCD), CpG/polyamidoamine-thioketal-adamantane (CpG/PAMAM-TK-Ad), and methoxy poly(ethylene glycol)-thioketal-adamantane (mPEG-TK-Ad). After intravenous injection and accumulation at the tumor site, the high level of reactive oxygen species in the tumor microenvironment promotes PIAN dissociation and the release of PPCD (mediating tumor cell killing and antigen release) and CpG/PAMAM (mediating antigen capturing and transferring to the tumor-draining lymph nodes). This results in antigen-presenting cell activation, antigen presentation, and robust antitumor immune responses. In combination with anti-PD-L1 antibody, the PIAN cures 40% of mice in a colorectal cancer model. This PIAN provides a new framework for designing programmable nanomedicine as in situ cancer vaccine for cancer immunotherapy.
利用纳米技术提高免疫疗法的效率是近年来的一个主要研究方向。然而，在使用单个纳米粒子来满足复杂的免疫激活过程中的所有要求时，存在矛盾和障碍。在此，报道了一种超分子组装的可编程免疫激活纳米医学（PIAN），用于在静脉注射后顺序完成多个步骤，并在原位引发强大的抗肿瘤免疫。可编程纳米医学是通过聚[（N-2-羟乙基）天冬酰胺]-Pt（IV）/β-环糊精（PPCD）、CpG/聚酰胺胺-硫代缩酮-金刚烷（CpG/PAMAM-TK-Ad）和甲氧基聚乙二醇-硫代缩酮-金刚烷（mPEG-TK-Ad）之间的主客体相互作用通过超分子组装构建的。静脉注射并在肿瘤部位积累后，肿瘤微环境中的高水平活性氧促进 PIAN 解离，释放 PPCD（介导肿瘤细胞杀伤和抗原释放）和 CpG/PAMAM（介导抗原捕获和转移到肿瘤引流淋巴结）。这导致抗原呈递细胞激活、抗原呈递和强大的抗肿瘤免疫反应。与抗 PD-L1 抗体结合，PIAN 在结直肠癌模型中治愈了 40%的小鼠。这种 PIAN 为设计可编程纳米医学作为原位癌症疫苗用于癌症免疫治疗提供了一个新的框架。
