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
孙艳菊 1陈文强 1孙硕 2商洪才 3关秀文 1张维芬1
作者信息
- 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
- 折叠
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.
Abstract
As a burgeoning combination tactic,cancer chemoimmunotherapy has brightened up the potential pos-sibility of conventional chemotherapy by virtue of the activa-tion 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 nano-platform coordinated ICD and immunoagonist was developed for boosted chemoimmunotherapy.ICD inducer doxorubicin(DOX)and immunoagonist unmethylated cytosine-phos-phate-guanine(CpG)were expediently co-hitchhiked by ca-tionic 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 tu-mor accumulation and excellent internalization in tumor cells through convenient intratumoral injection along with mini-mized systemic toxicity.DPC NP further triggered robust tumor ICD and instigated comprehensive antitumor im-munity under the assisted boosting of CpG immunoagonist.The availability of this DPC NP was further verified by the remarkable tumor inhibition in aggressive melanoma tumor-bearing mice.This work has presented a feasible and pro-mising paradigm nanoplatform to co-deliver various func-tional agents for boosted cancer chemoimmunotherapy.
关键词
cancer chemoimmunotherapy/"in situ"vaccine/im-munogenic cell death/immunoagonist/dendrimer nanoplatformKey words
cancer chemoimmunotherapy/"in situ"vaccine/im-munogenic cell death/immunoagonist/dendrimer nanoplatform引用本文复制引用
基金项目
National Natural Science Foundation of China(82102883)
出版年
2024
NETL
NSTL
万方数据