Tan Li , Gengjia Chen , Liteng Lin , Bo Li , Xiaobin Wang , Ye Chen , Wensou Huang , Mingyue Cai , Zecong Xiao , Xintao Shuai , Kangshun Zhu
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引用次数: 0
摘要
以氧化锰为基础的化学动力免疫疗法的发展正成为抗击实体瘤的关键策略。然而,纳米平台在诱导高效肿瘤治疗效果和产生显著抗肿瘤免疫反应方面的功效有限,这仍然是一个关键问题。在这项研究中,我们构建了一种新型多功能仿生物纳米疫苗,该疫苗由氧化锰负载的聚(2-二异丙基氨基乙基甲基丙烯酸酯)(MP)纳米颗粒和由氧化锰重塑的4T1细胞和树突状细胞(DCs)衍生的杂交细胞膜(RHM)包被层(统称为MP@RHM)组成,用于联合化学动力免疫疗法。与单细胞膜包被的纳米疫苗相比,MP@RHM纳米疫苗由于丰富的损伤相关分子模式、Mn2+和T细胞刺激分子的协同作用,能高效激活DC和T细胞,从而增强肿瘤特异性T细胞。瘤周注射 MP@RHM 纳米疫苗后,既能靶向肿瘤部位进行集中的化学动力治疗,又能靶向淋巴结进行强效的肿瘤特异性 T 细胞激活,从而实现高效的化学动力免疫治疗。此外,作为一种预防性癌症纳米疫苗,MP@RHM 还能产生强大的免疫记忆,抑制术后肿瘤转移和复发。我们的研究结果凸显了构建多功能仿生纳米疫苗用于针对实体瘤的个性化化学动力免疫疗法的前景。
Manganese oxide-constructed multifunctional biomimetic nanovaccine for robust tumor-specific T cell priming and chemodynamic therapy
The development of manganese oxide-based chemodynamic immunotherapy is emerging as a key strategy against solid tumors. However, the limited efficacy of nanoplatform in inducing efficient tumor therapeutic effects and creating the prominent antitumor immune responses remains a crucial issue. In this study, we construct a novel multifunctional biomimetic nanovaccine comprising manganese oxide-loaded poly(2-diisopropylaminoethyl methacrylate) (MP) nanoparticles and a coating layer of hybrid cell membrane (RHM) derived from manganese oxide-remodeled 4T1 cells and dendritic cells (DCs) (collectively called MP@RHM) for combination chemodynamic immunotherapy. Compared with the nanovaccines coated with the single cell membrane, the MP@RHM nanovaccine highly efficiently activates both DCs and T cells to boost tumor-specific T cell, owing to the synergistic effects of abundant damage-associated molecular patterns, Mn2+, and T cell-stimulating moieties. Upon peritumoral injection, the MP@RHM nanovaccine targets both the tumor site for focused chemodynamic therapy and the lymph nodes for robust tumor-specific T cell priming, thereby achieving highly efficient chemodynamic immunotherapy. Moreover, as a preventive cancer nanovaccine, MP@RHM generates strong immunological memory to inhibit postoperative tumor metastasis and recurrence. Our study findings highlight a promising approach to construct a multifunctional biomimetic nanovaccine for personalized chemodynamic immunotherapy against solid tumors.
期刊介绍:
Biomaterials is an international journal covering the science and clinical application of biomaterials. A biomaterial is now defined as a substance that has been engineered to take a form which, alone or as part of a complex system, is used to direct, by control of interactions with components of living systems, the course of any therapeutic or diagnostic procedure. It is the aim of the journal to provide a peer-reviewed forum for the publication of original papers and authoritative review and opinion papers dealing with the most important issues facing the use of biomaterials in clinical practice. The scope of the journal covers the wide range of physical, biological and chemical sciences that underpin the design of biomaterials and the clinical disciplines in which they are used. These sciences include polymer synthesis and characterization, drug and gene vector design, the biology of the host response, immunology and toxicology and self assembly at the nanoscale. Clinical applications include the therapies of medical technology and regenerative medicine in all clinical disciplines, and diagnostic systems that reply on innovative contrast and sensing agents. The journal is relevant to areas such as cancer diagnosis and therapy, implantable devices, drug delivery systems, gene vectors, bionanotechnology and tissue engineering.