Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Institute of Molecular Medicine, State Key Laboratory of Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.
Shanghai Key Laboratory of Gynecologic Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.
Angew Chem Int Ed Engl. 2021 Jul 5;60(28):15459-15465. doi: 10.1002/anie.202102631. Epub 2021 Jun 3.
A tumor-targeting enhanced chemotherapy, enabled by aptamer-drug conjugate nanomicelles, is reported that boosts antitumor immune responses. Multivalent aptamer drug conjugate (ApMDC), an amphiphilic telodendrimer consisting of a hydrophilic aptamer and a hydrophobic monodendron anchored with four anticancer drugs by acid-labile linkers, was designed and synthesized. By co-self-assembly with an ApMDC analogue, in which aptamer is replaced with polyethylene glycol, the surface aptamer density of these nanomicelles can be screened to reach an optimal complementation between blood circulation and tumor-targeting ability. Optimized nanomicelles can enhance immunogenic cell death of tumor cells, which strikingly augments the tumor-specific immune responses of the checkpoint blockade in immunocompetent tumor-bearing mice. ApMDC nanomicelles represent a robust platform for structure-function optimization of drug conjugates and nanomedicines.
一种基于适体-药物偶联纳米胶束的肿瘤靶向增强化疗被报道可以增强抗肿瘤免疫反应。多价适体药物偶联物（ApMDC）是一种两亲性树状大分子，由一个亲水适体和一个疏水单树突组成，通过酸不稳定键连接四个抗癌药物。通过与 ApMDC 类似物共自组装，其中适体被聚乙二醇取代，可以筛选这些纳米胶束的表面适体密度，以达到血液循环和肿瘤靶向能力之间的最佳互补。优化后的纳米胶束可以增强肿瘤细胞的免疫原性细胞死亡，从而显著增强免疫功能正常的荷瘤小鼠中检查点阻断的肿瘤特异性免疫反应。ApMDC 纳米胶束为药物偶联物和纳米药物的结构功能优化提供了一个强大的平台。
