Nitroxide radical conjugated ovalbumin theranostic nanosystem for enhanced dendritic cell-based immunotherapy and T1 magnetic resonance imaging

癌症研究 细胞毒性T细胞 纳米笼 生物相容性 黑色素瘤 骨髓 化学 卵清蛋白 免疫疗法 体内 免疫原性细胞死亡 医学 免疫系统 免疫学 生物 体外 有机化学 催化作用 生物技术 生物化学
作者
Yike Hou,Fei Kong,Zhe Tang,Rui Zhang,Dan Li,Jian Ge,Zhangsen Yu,Abdul Wahab,Yunyang Zhang,M. Zubair Iqbal,Xiangdong Kong
出处
期刊:Journal of Controlled Release [Elsevier BV]
卷期号:373: 547-563 被引量:16
标识
DOI:10.1016/j.jconrel.2024.07.050
摘要

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 using tumor vaccine-based nanomaterials, spotlighting their potential in revolutionizing melanoma treatment. This work employed organic nitrogen oxides, 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 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: they are 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
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