College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing 211816, China.
School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing 211816, China.
J Control Release. 2022 Oct;350:841-856. doi: 10.1016/j.jconrel.2022.09.009. Epub 2022 Sep 14.
Melanoma is a malignant skin cancer that is prone to metastasis in the early stage and has a poor prognosis. Immunomodulatory therapy for melanoma has been a hot research topic in recent years. However, low immune cell infiltration and loss of tumor immunogenicity may occur in tumors, resulting in low response rates to immunotherapy. Thus, immunomodulatory therapy is usually used in combination with chemotherapy and radiotherapy. Development of combined therapeutic strategies with low systemic toxicity, high immune responsiveness and long-term inhibition of metastasis and recurrence of melanoma is the goal of current research. In this study, the insoluble immune adjuvant imiquimod (R837) was prepared as nanocrystals and coated with polydopamine (PDA) to form R837@PDA, which was then loaded into chitosan hydrogel (CGP) to form the drug-loaded gel system, R837@PDA@CGP (RPC), to combine immunomodulation effects, induction of immunogenic cell death (ICD) effects and immune-enhancement effects. After treatment with RPC, ICD in melanoma was induced, and the infiltration rate of cytotoxic T cells (CTLs) in melanoma was also significantly enhanced, which turned the tumor itself into an in situ vaccine and boosted the cancer-immunity cycle at the tumor site. Therefore, melanoma growth, metastasis and recurrence were notably inhibited.
黑色素瘤是一种恶性皮肤癌，早期易发生转移，预后较差。近年来，黑色素瘤的免疫调节治疗已成为研究热点。然而，肿瘤中可能会发生免疫细胞浸润低和肿瘤免疫原性丧失，导致免疫治疗的反应率低。因此，免疫调节治疗通常与化疗和放疗联合使用。开发具有低全身毒性、高免疫应答性和长期抑制黑色素瘤转移和复发的联合治疗策略是当前研究的目标。在本研究中，将不溶性免疫佐剂咪喹莫特（R837）制备成纳米晶体，并包覆聚多巴胺（PDA）形成 R837@PDA，然后将其载入壳聚糖水凝胶（CGP）中形成载药凝胶系统 R837@PDA@CGP（RPC），以结合免疫调节作用、诱导免疫原性细胞死亡（ICD）效应和免疫增强效应。用 RPC 处理后，黑色素瘤中诱导了 ICD，黑色素瘤中细胞毒性 T 细胞（CTL）的浸润率也显著增强，使肿瘤本身成为原位疫苗，并在肿瘤部位增强了癌症免疫循环。因此，显著抑制了黑色素瘤的生长、转移和复发。
