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无机纳米生物材料助力肿瘤免疫治疗:策略与应用

Inorganic Nanobiomaterials Boost Tumor Immunotherapy: Strategies and Applications.

作者信息

Meng Qi, Ding Binbin, Ma Ping'an, Lin Jun

机构信息

State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China.

School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, 230026, China.

出版信息

Acc Chem Res. 2025 Apr 15;58(8):1210-1223. doi: 10.1021/acs.accounts.4c00843. Epub 2025 Apr 3.


DOI:10.1021/acs.accounts.4c00843
PMID:40179239
Abstract

ConspectusTumor immunotherapy, as a new antitumor method to fight cancer by activating or enhancing the body's own immune system, has been extensively studied and applied in clinical practice. However, as an extremely complex system, tumor heterogeneity and complex immunosuppressive tumor microenvironment (TME) lead to poor immune response rate or secondary drug resistance. The advent of nanotechnology has ushered in a new era for immunotherapy. In particular, inorganic nanomaterials, with their unique physicochemical properties and excellent biocompatibility, are becoming an important tool for enhancing immunotherapy. Inorganic nanomaterials can be used as carriers for immune agents, improving drug delivery efficiency and thereby reducing systemic immunotoxicity and enhancing immune responses. Inorganic nanomaterials also trigger tumor immunogenic cell death (ICD), stimulate antitumor immune responses, and alleviate immunosuppressive TME by increasing oxygen levels, modulating metabolic pathways, and altering the secretion of immunosuppressive cytokines. The synergistic integration of inorganic nanomaterials with immunotherapy adeptly navigates around the constraints of conventional treatments, reducing side effects while concurrently augmenting therapeutic efficacy. In this review, we summarize our recent efforts in the design and synthesis of inorganic nanobiomaterials to enhance the efficacy of tumor immunotherapy. These nanomaterials achieve the desired immune efficacy mainly through four strategies, including inducing ICD, developing tumor nanovaccines, activating pyroptosis, and regulating tumor metabolism, providing beneficial implications for tumor immunotherapy. For one thing, due to the deficiency of ICD effect in single therapy, we mainly developed nanocatalysts that integrate multiple therapeutic functions to play a catalytic role in TME, converting tumor substances or metabolites into therapeutic products in situ, and further enhancing ICD. For another, in order to solve the problems of low antigen loading and therapeutic efficiency of existing adjuvants, several novel multifunctional nanoadjuvants were prepared, which combine high antigen loading and multimode therapeutic function in one, and achieve efficient immune activation. Moreover, to attain strong inflammatory responses and immunogenicity, we engineer pyroptosis adjuvants that selectively induce tumor cell pyroptosis by enhancing intracellular oxidative stress or ion overload. Finally, to reverse the immunosuppressive microenvironment, we developed nanoplatforms that target tumor metabolism, altering the levels of nutrients and metabolites in tumor such as glucose, lactic acid, citric acid, and tryptophan to effectively alter the TME, thereby activating and enhancing the body's immune response. The implementation of these strategies not only improves the therapeutic effect but also reduces the side effects and provides valuable insights and references for the development of novel nanomaterials to assist immunotherapy.

摘要

综述 肿瘤免疫疗法作为一种通过激活或增强机体自身免疫系统来对抗癌症的新型抗肿瘤方法,已在临床实践中得到广泛研究和应用。然而,作为一个极其复杂的系统,肿瘤异质性和复杂的免疫抑制肿瘤微环境(TME)导致免疫应答率低下或继发耐药性。纳米技术的出现为免疫疗法开创了一个新时代。特别是无机纳米材料,凭借其独特的物理化学性质和优异的生物相容性,正成为增强免疫疗法的重要工具。无机纳米材料可用作免疫剂的载体,提高药物递送效率,从而降低全身免疫毒性并增强免疫应答。无机纳米材料还可引发肿瘤免疫原性细胞死亡(ICD),刺激抗肿瘤免疫应答,并通过提高氧水平、调节代谢途径和改变免疫抑制细胞因子的分泌来缓解免疫抑制性TME。无机纳米材料与免疫疗法的协同整合巧妙地规避了传统治疗的局限性,在降低副作用的同时提高了治疗效果。在这篇综述中,我们总结了我们最近在设计和合成无机纳米生物材料以提高肿瘤免疫疗法疗效方面所做的努力。这些纳米材料主要通过四种策略实现了理想的免疫效果,包括诱导ICD、开发肿瘤纳米疫苗、激活细胞焦亡和调节肿瘤代谢,为肿瘤免疫疗法提供了有益的启示和参考。一方面,由于单一疗法中ICD效应的不足,我们主要开发了整合多种治疗功能的纳米催化剂,在TME中发挥催化作用,将肿瘤物质或代谢产物原位转化为治疗产物,进一步增强ICD。另一方面,为了解决现有佐剂抗原负载量低和治疗效率低的问题,我们制备了几种新型多功能纳米佐剂,它们将高抗原负载量和多模式治疗功能集于一体,实现了高效的免疫激活。此外,为了获得强烈的炎症反应和免疫原性,我们设计了细胞焦亡佐剂,通过增强细胞内氧化应激或离子过载来选择性诱导肿瘤细胞焦亡。最后,为了逆转免疫抑制微环境,我们开发了靶向肿瘤代谢的纳米平台,改变肿瘤中葡萄糖、乳酸、柠檬酸和色氨酸等营养物质和代谢产物的水平,有效改变TME,从而激活和增强机体的免疫应答。这些策略的实施不仅提高了治疗效果,还降低了副作用,为开发辅助免疫疗法的新型纳米材料提供了有价值的见解和参考。

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