Institute of Smart Biomedical Materials, School of Materials Science and Engineering, Zhejiang Sci-Tech University, Hangzhou 310018, PR China; Zhejiang-Mauritius Joint Research Center for Biomaterials and Tissue Engineering, Zhejiang Sci-Tech University, Hangzhou 310018, PR China.
Institute of Smart Biomedical Materials, School of Materials Science and Engineering, Zhejiang Sci-Tech University, Hangzhou 310018, PR China; Zhejiang-Mauritius Joint Research Center for Biomaterials and Tissue Engineering, Zhejiang Sci-Tech University, Hangzhou 310018, PR China; South China Advanced Institute for Soft Matter Science and Technology, School of Emergent Soft Matter, Guangdong Provincial Key Laboratory of Functional and Intelligent Hybrid Materials and Devices, South China University of Technology, Guangzhou 510640, PR China.
J Control Release. 2024 Sep;373:547-563. doi: 10.1016/j.jconrel.2024.07.050. Epub 2024 Jul 29.
Melanoma, known for its aggressive metastatic nature, presents a formidable challenge in cancer treatment, where conventional therapies often fall short. This study introduces a pioneering approach utilizing metal-free nanosystem as tumor vaccines, spotlighting their potential in revolutionizing melanoma treatment. This work employed organic nitroxides, specifically 4-carboxy-TEMPO, in combination with chitosan (CS), to create a novel nanocomposite material - the CS-TEMPO-OVA nanovaccines. This composition not only improves biocompatibility and extends blood circulation time of TEMPO but also marks a significant departure from traditional gadolinium-based contrast agents in MRI technology, addressing safety concerns. CS-TEMPO-OVA nanovaccines demonstrate excellent biocompatibility at both the cellular and organoid level. They effectively stimulate bone marrow-derived dendritic cells (BMDCs), which in turn promote the maturation and activation of T cells. This ultimately leads to a strong production of essential cytokines. These nanovaccines serve a dual purpose as both therapeutic and preventive. By inducing an immune response, activating cytotoxic T cells, and promoting macrophage M1 polarization, they effectively inhibit melanoma growth and enhance survival in mouse models. When combined with αPD-1, the CS-TEMPO-OVA nanovaccines significantly bolster the infiltration of cytotoxic T lymphocytes (CTLs) within tumors, sparking a powerful systemic antitumor response that effectively curbs tumor metastasis. The ability of these nanovaccines to control both primary (subcutaneous) and metastatic B16-OVA tumors highlights their remarkable efficacy. Furthermore, the CS-TEMPO-OVA nanovaccine can be administered in vivo via both intravenous and intramuscular routes, both of which effectively enhance the T contrast of magnetic resonance imaging in tumor tissue. This study offers invaluable insights into the integrated application of these nanovaccines in both clinical diagnostics and treatment, marking a significant stride in cancer research and patient care.
黑色素瘤以其侵袭性和转移性而闻名，是癌症治疗中的一个巨大挑战，传统疗法往往力不从心。本研究引入了一种利用无金属纳米系统作为肿瘤疫苗的开创性方法，强调了其在颠覆黑色素瘤治疗方面的潜力。本工作采用有机氮氧自由基，特别是 4-羧基-TEMPO，与壳聚糖（CS）结合，制备了一种新型纳米复合材料 - CS-TEMPO-OVA 纳米疫苗。这种组合不仅提高了 TEMPO 的生物相容性和血液循环时间，而且在 MRI 技术中与传统的基于钆的对比剂相比，具有显著的安全性优势。CS-TEMPO-OVA 纳米疫苗在细胞和类器官水平均表现出良好的生物相容性。它们有效地刺激骨髓来源的树突状细胞（BMDCs），进而促进 T 细胞的成熟和激活。这最终导致必需细胞因子的强烈产生。这些纳米疫苗具有治疗和预防的双重作用。通过诱导免疫反应、激活细胞毒性 T 细胞和促进巨噬细胞 M1 极化，它们有效地抑制黑色素瘤的生长，并提高小鼠模型的存活率。当与 αPD-1 联合使用时，CS-TEMPO-OVA 纳米疫苗可显著增强肿瘤内细胞毒性 T 淋巴细胞（CTL）的浸润，引发强大的系统抗肿瘤反应，有效抑制肿瘤转移。这些纳米疫苗控制原发性（皮下）和转移性 B16-OVA 肿瘤的能力突出了其显著的疗效。此外，CS-TEMPO-OVA 纳米疫苗可通过静脉内和肌肉内途径在体内给药，这两种途径均可有效增强肿瘤组织中磁共振成像的 T 对比。本研究为这些纳米疫苗在临床诊断和治疗中的综合应用提供了宝贵的见解，标志着癌症研究和患者护理的重大进展。
