ICD和免疫激动剂协作的树形高分子纳米平台作为极简“原位”肿瘤疫苗用于高效化学免疫治疗  

Minimalist“in situ”tumor vaccine leveraging versatile dendrimer nanoplatform coordinated ICD and immunoagonist for boosted chemoimmunotherapy

作　　者：孙艳菊 陈文强 孙硕 商洪才 关秀文 张维芬 Yanju Sun;Wenqiang Chen;Shuo Sun;Hongcai Shang;Xiuwen Guan;Weifen Zhang(College of Pharmacy,Shandong Second Medical University,Weifang 261053,China;School of Clinical Medicine,Shandong Second Medical University,Weifang 261053,China;Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing,Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine,Beijing 100700,China)

机构地区：[1]College of Pharmacy,Shandong Second Medical University,Weifang 261053,China [2]School of Clinical Medicine,Shandong Second Medical University,Weifang 261053,China [3]Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing,Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine,Beijing 100700,China

出　　处：《Science China Materials》2024年第8期2700-2708,共9页中国科学（材料科学）（英文版）

基　　金：the National Natural Science Foundation of China(82102883)for financial support to this work。

摘　　要：作为一种新兴的联合治疗策略,肿瘤化学免疫治疗拓展了传统化疗药物的潜在可能性,利用某些化疗药物诱发免疫原性细胞死亡(ICD)激活抗肿瘤免疫应答,提升肿瘤治疗效率.本文设计了一种ICD和免疫激动剂协作的树形高分子纳米平台作为极简“原位”肿瘤疫苗用于高效的化学免疫治疗.利用树状高分子PAMAM担载ICD引发药物DOX以及免疫激动剂CpG,该DOX@PAMAM/CpG(简称DPC)纳米粒子物理性能适宜,通过便捷的瘤内注射可在肿瘤组织良好蓄积和内化,并最大限度地降低全身毒性.在CpG的协助下该纳米粒子可引发强劲的ICD并激活全面的抗肿瘤免疫反应,体内动物实验证实该DPC纳米粒子对侵袭性黑色素瘤具有显著的抑制.本研究为肿瘤化学免疫治疗纳米递药平台的构建提供了一种切实可行的策略.As a burgeoning combination tactic,cancer chemoimmunotherapy has brightened up the potential possibility of conventional chemotherapy by virtue of the activation capacity on antitumor immunity induced by certain chemotherapeutic agents through tumor immunogenic cell death(ICD)pathway,which has collaboratively promoted the therapeutic outcome against malignancies.Here,a minimalist“in situ”tumor vaccine leveraging versatile dendrimer nanoplatform coordinated ICD and immunoagonist was developed for boosted chemoimmunotherapy.ICD inducer doxorubicin(DOX)and immunoagonist unmethylated cytosine-phosphate-guanine(CpG)were expediently co-hitchhiked by cationic dendrimer polyamidoamine(PAMAM),with DOX packaged in the hydrophobic core and CpG adsorbed on the positive PAMAM surface.The constructed DOX@PAMAM/CpG nanoparticle(DPC NP)presented suitable physical characteristics and could be employed as a minimalist“in situ”tumor vaccine nanoplatform,which endowed competent tumor accumulation and excellent internalization in tumor cells through convenient intratumoral injection along with minimized systemic toxicity.DPC NP further triggered robust tumor ICD and instigated comprehensive antitumor immunity under the assisted boosting of CpG immunoagonist.The availability of this DPC NP was further verified by the remarkable tumor inhibition in aggressive melanoma tumorbearing mice.This work has presented a feasible and promising paradigm nanoplatform to co-deliver various functional agents for boosted cancer chemoimmunotherapy.

关 键 词：化学免疫治疗 瘤内注射 药物诱发 全身毒性 肿瘤疫苗 激动剂 黑色素瘤 树状高分子 

分 类 号：TQ460.1[化学工程—制药化工] TB383.1[一般工业技术—材料科学与工程] R730.51[医药卫生—肿瘤]