一种自佐剂光热碳点纳米疫苗用于鼻咽癌的多模式治疗与预防

文献信息

中文摘要

开发一种整合治疗与预防的“全周期”策略仍是抗击鼻咽癌（NPC）的核心挑战。在此，通过将负载丰加霉素（Toy）的氧化还原响应性碳点簇（CDCs）包覆同源癌细胞膜（CCMs），设计了一种仿生纳米疫苗（CDC/Toy@CCM）。所得纳米疫苗平均粒径为70.7 nm，具有高载药量（12.3%）和优异的光热转换效率（48.7%）。该纳米疫苗利用CCMs的同源靶向能力实现精准肿瘤归巢，而二硫键交联的CDCs能够在肿瘤微环境中实现谷胱甘肽触发的药物释放，从而进行可控化疗。在近红外激光照射下，CDCs对原发肿瘤产生强烈的光热消融，化疗与光热治疗（PTT）的联合有效诱导免疫原性细胞死亡（ICD），协同CDCs的自佐剂作用与CCM抗原，在双侧NPC小鼠模型中产生显著的抗肿瘤反应，抑制原发和远端肿瘤。在预防性设置中，纳米疫苗预接种可对后续肿瘤攻击产生有效的免疫保护。这项工作提供了一种有前景的“全周期”纳米平台，协同整合PTT、化疗和免疫治疗，用于NPC的治疗和预防。

英文摘要

Developing a "full-cycle" strategy that integrates both treatment and prophylaxis remains a central challenge against nasopharyngeal carcinoma (NPC). Here, a biomimetic nanovaccine (CDC/Toy@CCM) is designed by coating toyocamycin (Toy)-loaded redox-responsive carbon dot clusters (CDCs) with homologous cancer cell membranes (CCMs). The obtained nanovaccine exhibits an average size of 70.7 nm, a high drug loading capacity (12.3%), and a superior photothermal conversion efficiency of 48.7%. The nanovaccine leverages the homologous targeting capacity of CCMs for precise tumor homing, while the disulfide-cross-linked CDCs enable glutathione-triggered drug release specifically within the tumor microenvironment for controlled chemotherapy. Under near-infrared laser irradiation, the CDCs generate robust photothermal ablation of primary tumors, and the combination of chemotherapy and photothermal therapy (PTT) effectively induces immunogenic cell death (ICD), which synergizes the self-adjuvant of CDCs and CCM antigens to generate significant antitumor response to suppress both primary and distant tumors in a bilateral NPC mouse model. In a prophylactic setting, the nanovaccine pre-vaccination generates effective immune protection against subsequent tumor challenge. This work provides a promising "full-cycle" nanoplatform that synergistically integrates PTT, chemotherapy, and immunotherapy for both NPC treatment and prophylaxis.