School of Pharmaceutical Sciences, Sun Yat-sen University, University Town, Guangzhou 510006, China.
College of Pharmacy, Jinan University, Guangzhou 510632, China.
ACS Appl Mater Interfaces. 2020 Jul 22;12(29):32259-32269. doi: 10.1021/acsami.0c05090. Epub 2020 May 22.
In this study, an ingenious core-shell structure microneedle (CSMN) array was designed to synergistically boost robust immune response by the intralesional codelivery of photosensitizer and indoleamine 2,3-dioxygenase (IDO) blockade. Photosensitizer indocyanine green was encapsulated into chitosan nanoparticles (ICG-NPs), followed by concentrating on the tip shell of microneedles. 1-Methyl-tryptophan was loaded into the cross-linked poly(vinyl pyrrolidone) and poly(vinyl alcohol) gel as the microneedle core. Through the direct deposition of the ICG-NP-loaded tips into the tumor site with uniform spatial distribution, the CSMNs effectively converted the near-infrared laser into heat to ablate primary tumors, generated tumor-associated antigens and damage-associated molecular patterns, and promoted the maturation of dendritic cells and the secretion of immunostimulatory cytokines. The IDO blockade further reversed the IDO-mediated immunosuppression, ultimately arousing an effective systematic immune response. The results showed that 80% of the melanoma tumor was eradicated, followed by a relapse-free survival in more than 120 days. Of note, this synergistic strategy significantly inhibited lung metastasis and controlled the development of already metastasized tumors. Our work provides a new, generalizable framework for using the microneedle-based photothermal therapy to initiate antitumor immunity and sensitize tumors to IDO blockade.
在这项研究中，设计了一种巧妙的核壳结构微针（CSMN）阵列，通过光敏剂和吲哚胺 2,3-双加氧酶（IDO）阻断的腔内共递送来协同增强强大的免疫反应。将光敏剂吲哚菁绿封装到壳聚糖纳米颗粒（ICG-NPs）中，然后浓缩到微针的尖端壳层。1-甲基色氨酸被加载到交联的聚（乙烯基吡咯烷酮）和聚（乙烯醇）凝胶中作为微针的核心。通过将负载 ICG-NP 的尖端直接沉积到具有均匀空间分布的肿瘤部位，CSMNs 有效地将近红外激光转化为热量来消融原发性肿瘤，产生肿瘤相关抗原和损伤相关分子模式，并促进树突状细胞的成熟和免疫刺激细胞因子的分泌。IDO 阻断进一步逆转了 IDO 介导的免疫抑制，最终引起有效的系统免疫反应。结果表明，80%的黑色素瘤肿瘤被根除，随后 120 天以上无复发的存活率。值得注意的是，这种协同策略显著抑制了肺转移并控制了已经转移的肿瘤的发展。我们的工作为利用基于微针的光热疗法引发抗肿瘤免疫和使肿瘤对 IDO 阻断敏感提供了一个新的、可推广的框架。
