组会讲课人员:梁惠闲
Supramolecular Assembled Programmable Nanomedicine As In Situ Cancer Vaccine for Cancer Immunotherapy
超分子组装可编程纳米药物作为原位癌疫苗用于癌症免疫治疗
主讲人:梁惠闲
Advanced Materials | January 2021 | Volume 33, Issue 7 | 2007293 |https://doi.org/10.1002/adma.202007293
Abstract:
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.
摘要:
利用纳米技术提高免疫治疗效率是近年来的主要研究兴趣。然而,使用单个纳米颗粒来满足复杂免疫激活过程中的所有要求是有矛盾和障碍的。本文报道了一种超分子组装的可编程免疫激活纳米药物(PIAN),用于在静脉注射后连续完成多个步骤,并在原位诱导强大的抗肿瘤免疫。可编程纳米药物是通过聚-[(N-2-羟乙基)-天冬酰胺]-Pt(IV)/β-环糊精(PPCD)、CpG/聚酰胺-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。在肿瘤部位静脉注射和积聚后,肿瘤微环境中的高水平活性氧促进了PIAN的分离和PPCD(介导肿瘤细胞杀伤和抗原释放)和CpG/PAMAM(介导抗原捕获和传递到肿瘤引流淋巴结)的释放。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。结合抗PD-L1抗体,该药物可治愈40%的结直肠癌模型小鼠。PIAN为设计可编程纳米药物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。