Institute of Functional Nano & Soft Materials (FUNSOM), Soochow University, Suzhou, Jiangsu, 215123, China.
Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, 199 Ren'ai Rd, Suzhou, Jiangsu, 215123, China.
Small. 2023 Nov;19(46):e2303634. doi: 10.1002/smll.202303634. Epub 2023 Jul 19.
Despite the rapid development of the immune checkpoint blockade (ICB) in melanoma treatment, the immunosuppressive tumor microenvironment (TME) still hinders the efficacy of immunotherapy. Recently, using agonists to modulate the TME have presented promising clinical responses in combination with ICB therapies. However, local intratumoral injection as the commonly used administration route for immune agonists would lead to low patient compliance. Herein, it is demonstrated that fluorocarbon modified chitosan (FCS) can self-assemble with immune adjuvant polyriboinosinic:polyribocytidylic acid (poly(I:C)), forming nanoparticles that can penetrate through cutaneous barriers to enable transdermal delivery. FCS/poly(I:C) can efficiently activate various types of cells presented on the transdermal route (through the skin into the TME), leading to IRF3-mediated IFN-β induction in the activated cells for tumor repression. Furthermore, transdermal FCS/poly(I:C) treatment can significantly magnify the efficacy of the programmed cell death protein 1 (PD-1) blockade in melanoma treatment through activating the immunosuppressive TME. This study approach offered an attractive transdermal approach in combined with ICB therapy for combined immunotherapy, particularly suitable for melanoma treatment.
尽管免疫检查点阻断（ICB）在黑色素瘤治疗方面发展迅速，但免疫抑制性肿瘤微环境（TME）仍然阻碍了免疫疗法的疗效。最近，使用激动剂来调节 TME 与 ICB 治疗联合已显示出有希望的临床反应。然而，免疫激动剂的常用给药途径——局部瘤内注射会导致患者顺应性低。本文证明，氟碳改性壳聚糖（FCS）可以与免疫佐剂聚肌苷酸：聚胞苷酸（poly(I:C)) 自组装，形成纳米颗粒，可穿透皮肤屏障实现经皮给药。FCS/poly(I:C) 可以有效地激活经皮途径（通过皮肤进入 TME）上存在的各种类型的细胞，导致激活细胞中的干扰素调节因子 3 (IRF3) 介导的 IFN-β诱导，从而抑制肿瘤。此外，经皮 FCS/poly(I:C) 治疗可以通过激活免疫抑制性 TME 显著提高程序性细胞死亡蛋白 1 (PD-1) 阻断在黑色素瘤治疗中的疗效。该研究方法为联合 ICB 治疗的联合免疫疗法提供了一种有吸引力的经皮方法，特别适用于黑色素瘤的治疗。
