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针对肿瘤微环境中血管生成和免疫功能障碍的纳米治疗方法。

Nanotherapeutic approaches targeting angiogenesis and immune dysfunction in tumor microenvironment.

机构信息

Department of Biomedical Engineering, College of Engineering, Peking University, Beijing, 100871, China.

出版信息

Sci China Life Sci. 2018 Apr;61(4):380-391. doi: 10.1007/s11427-017-9256-1. Epub 2018 Mar 27.

Abstract

Tumor microenvironment (TME) comprising cellular and non-cellular components is a major source of cancer hallmarks. Notably, angiogenesis responsible for normal physiological remodeling process can otherwise harness vessel abnormalities during tumorigenesis eliciting severe therapeutic inefficiency. Currently, FDA approved antiangiogenic drugs have only shown modest clinical success owing to tumor hypoxia, antiangiogenic therapeutic resistance, and limited knowledge in understanding TME. In order to overcome these limitations, targeting angiogenesis combined with immunosuppressive TME could offer potential therapeutic opportunities. Indeed, these therapeutic approaches can be further revisited with the advent of nanotechnology that can target the key cellular components of TME and tumor cells more precisely. Synergetic targeting without eliciting systemic toxicity achieved by integration of antiangiogenic and immunotherapy in a single nanoplatform is vital for therapeutic success. In this review, we will discuss the most promising nanotechnological advancements oriented to modulate the immunosuppressive TME in association with antiangiogenic therapy that has gained immense popularity in cancer treatment.

摘要

肿瘤微环境(TME)由细胞和非细胞成分组成,是癌症标志的主要来源。值得注意的是,血管生成负责正常的生理重塑过程,但在肿瘤发生时可以利用血管异常,导致严重的治疗效率低下。目前,美国食品和药物管理局(FDA)批准的抗血管生成药物仅显示出适度的临床成功,这是由于肿瘤缺氧、抗血管生成治疗耐药性以及对 TME 理解有限。为了克服这些限制,靶向血管生成并结合免疫抑制性 TME 可能提供潜在的治疗机会。事实上,随着纳米技术的出现,这些治疗方法可以进一步重新审视,纳米技术可以更精确地靶向 TME 的关键细胞成分和肿瘤细胞。通过将抗血管生成和免疫疗法整合到单个纳米平台中,实现协同靶向而不引起全身毒性,对于治疗成功至关重要。在这篇综述中,我们将讨论最有前途的纳米技术进展,这些进展旨在调节与抗血管生成治疗相关的免疫抑制性 TME,这种治疗方法在癌症治疗中已经得到了广泛的关注。

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