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用于癌症免疫治疗的合成与生物纳米颗粒。

Synthetic and biological nanoparticles for cancer immunotherapy.

作者信息

Oliveira Inês, Rodrigues-Santos Paulo, Ferreira Lino, Pires das Neves Ricardo

机构信息

Center for Neuroscience and Cell Biology (CNC), University of Coimbra, 3004-504 Coimbra, Portugal.

Center for Innovation in Biomedicine and Biotechnology (CIBB), University of Coimbra, 3004-504 Coimbra, Portugal.

出版信息

Biomater Sci. 2024 Nov 19;12(23):5933-5960. doi: 10.1039/d4bm00995a.

Abstract

Cancer is becoming the main public health problem globally. Conventional chemotherapy approaches are slowly being replaced or complemented by new therapies that avoid the loss of healthy tissue, limit off-targets, and eradicate cancer cells. Immunotherapy is nowadays an important strategy for cancer treatment, that uses the host's anti-tumor response by activating the immune system and increasing the effector cell number, while, minimizing cancer's immune-suppressor mechanisms. Its efficacy is still limited by poor therapeutic targeting, low immunogenicity, antigen presentation deficiency, impaired T-cell trafficking and infiltration, heterogeneous microenvironment, multiple immune checkpoints and unwanted side effects, which could benefit from improved delivery systems, able to release immunotherapeutic agents to tumor microenvironment and immune cells. Nanoparticles (NPs) for immunotherapy (Nano-IT), have a huge potential to solve these limitations. Natural and/or synthetic, targeted and/or stimuli-responsive nanoparticles can be used to deliver immunotherapeutic agents in their native conformations to the site of interest to enhance their antitumor activity. They can also be used as co-adjuvants that enhance the activity of IT effector cells. These nanoparticles can be engineered in the natural context of cell-derived extracellular vesicles (EVs) or exosomes or can be fully synthetic. In this review, a detailed SWOT analysis is done through the comparison of engineered-synthetic and naturaly-derived nanoparticles in terms of their current and future use in cancer immunotherapy.

摘要

癌症正成为全球主要的公共卫生问题。传统化疗方法正逐渐被新疗法所取代或补充,这些新疗法可避免健康组织受损、限制脱靶效应并根除癌细胞。免疫疗法如今是癌症治疗的一项重要策略,它通过激活免疫系统、增加效应细胞数量,同时尽量减少癌症的免疫抑制机制来利用宿主的抗肿瘤反应。其疗效仍受限于治疗靶向性差、免疫原性低、抗原呈递缺陷、T细胞运输和浸润受损、微环境异质性、多个免疫检查点以及不良副作用,而改进的递送系统可能会带来益处,这种系统能够将免疫治疗药物释放到肿瘤微环境和免疫细胞中。用于免疫治疗的纳米颗粒(Nano-IT)在解决这些局限性方面具有巨大潜力。天然和/或合成的、靶向和/或刺激响应性纳米颗粒可用于将处于天然构象的免疫治疗药物递送至感兴趣的部位,以增强其抗肿瘤活性。它们还可作为共佐剂来增强免疫治疗效应细胞的活性。这些纳米颗粒可以在细胞衍生的细胞外囊泡(EVs)或外泌体的天然环境中进行工程改造,也可以完全合成。在本综述中,通过比较工程合成纳米颗粒和天然来源纳米颗粒在癌症免疫治疗中的当前及未来应用,进行了详细的SWOT分析。

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