Rod-Scale Design Strategies for Immune-Targeted Delivery System toward Cancer Immunotherapy
Rod-Scale Design Strategies for Immune-Targeted Delivery System toward Cancer Immunotherapy
复制标题
DOI：
10.1021/acsnano.9b01271
复制
发表时间：
2019-07-01
期刊：
影响因子：
17.1
通讯作者：
Ohno, Tadao
中科院分区：
文献类型：
--
作者：
Wang, Xiupeng;Ihara, Shu;Ohno, Tadao
加强抗肿瘤免疫反应，突破免疫抑制肿瘤微环境的激活能屏障，是肿瘤免疫治疗的一个活跃领域。新出现的证据表明，借助载体系统输送免疫刺激分子对于癌症免疫治疗是必不可少的。然而，递送系统对免疫靶点和抗癌免疫反应的大小依赖效应尚未得到全面了解。在这里，为了阐明递送系统对潜在的抗癌免疫机制的尺寸依赖效应，设计了长度从100 nm到10微米的棒状羟基磷灰石(HA)颗粒。HA棒以一种大小依赖的方式刺激抗癌免疫。长度从100到500 nm的较短的HA棒促进抗原细胞摄取、树突状细胞(DC)成熟和淋巴结靶向抗原。相反，长度从500 nm到10微米的较长HA棒延长了抗原保留时间，并增加了DC的聚集。长度为500 nm的中等尺寸HA棒，利用短棒和长棒的优势，显示出优化的抗原释放和摄取，增加了DC的聚集和成熟，最高的CD4(+)和CD8(+)T细胞群，以及最好的体内抗癌免疫。本研究为未来针对癌症免疫治疗的免疫靶向递送系统提供了一种杆状规模的设计策略。
Strengthening the antitumor immune response to surpass the activation energy barrier associated with the immunosuppressive tumor microenvironment is an active area of cancer immunotherapy. Emerging evidence suggests that delivery of immunostimulatory molecules with the aid of a carrier system is essential for cancer immunotherapy. However, the size-dependent effect of the delivery system on immune-targeted sites and anticancer immune responses is yet to be comprehensively understood. Herein, to clarify the size-dependent effect of the delivery system on the underlying anticancer immune mechanism, rod-shaped hydroxyapatite (HA) particles with lengths from 100 nm to 10 mu m are designed. HA rods stimulate anticancer immunity in a size-dependent manner. Shorter HA rods with lengths ranging from 100 to 500 nm promote antigen cellular uptake, dendritic cell (DC) maturation, and lymph node targeting antigen. In contrast, longer HA rods with lengths ranging from 500 nm to 10 mu m prolong antigen retention and increase DC accumulation. Medium-sized HA rods with a length of 500 nm, taking advantage of both short and long rods, show optimized antigen release and uptake, increased DCs accumulation and maturation, highest CD4(+) and CD8(+) T cell population, and the best anticancer immunity in vivo. The present study provides a rod-scale design strategy for an immune-targeted delivery system toward cancer immunotherapy in the future.