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纳米技术与卵巢癌免疫治疗:探索新领域。

Nanotechnology and Immunotherapy in Ovarian Cancer: Tracing New Landscapes.

机构信息

Department of Nanomedicine, Houston Methodist Research Institute, Houston, Texas (B.C., S.P., R.S.C., M.F.); Swansea University Medical School, Singleton Park, Swansea, United Kingdom (B.C., S.P., R.S.C.); and Department of Medicine, Weill Cornell Medical College, New York, New York (M.F.)

Department of Nanomedicine, Houston Methodist Research Institute, Houston, Texas (B.C., S.P., R.S.C., M.F.); Swansea University Medical School, Singleton Park, Swansea, United Kingdom (B.C., S.P., R.S.C.); and Department of Medicine, Weill Cornell Medical College, New York, New York (M.F.).

出版信息

J Pharmacol Exp Ther. 2019 Sep;370(3):636-646. doi: 10.1124/jpet.118.254979. Epub 2019 Feb 8.

Abstract

Ovarian cancer (OC) is the seventh most common cancer in women worldwide. Standard therapeutic treatments involve debulking surgery combined with platinum-based chemotherapies. Of the patients with advanced-stage cancer who initially respond to current treatments, 50%-75% relapse. Immunotherapy-based approaches aimed at boosting antitumor immunity have recently emerged as promising tools to challenge tumor progression. Treatments with inhibitors of immune checkpoint molecules have shown impressive results in other types of tumors. However, only 15% of checkpoint inhibitors evaluated have proven successful in OC due to the immunosuppressive environment of the tumor and the transport barriers. This limits the efficacy of the existing immunotherapies. Nanotechnology-based delivery systems hold the potential to overcome such limitations. Various nanoformulations including polymeric, liposomes, and lipid-polymer hybrid nanoparticles have already been proposed to improve the biodistribution and targeting capabilities of drugs against tumor-associated immune cells, including dendritic cells and macrophages. In this review, we examine the impact of immunotherapeutic approaches that are currently under consideration for the treatment of OC. In this review, we also provide a comprehensive analysis of the existing nanoparticle-based synthetic strategies and their limitations and advantages over standard treatments. Furthermore, we discuss how the strength of the combination of nanotechnology with immunotherapy may help to overcome the current therapeutic limitations associated with their individual application and unravel a new paradigm in the treatment of this malignancy.

摘要

卵巢癌 (OC) 是全球女性中第七种最常见的癌症。标准的治疗方法包括肿瘤细胞减灭术联合铂类化疗。在最初对现有治疗方法有反应的晚期癌症患者中,有 50%-75%会复发。基于免疫疗法的方法旨在增强抗肿瘤免疫力,最近已成为挑战肿瘤进展的有前途的工具。免疫检查点分子抑制剂的治疗在其他类型的肿瘤中已显示出令人印象深刻的效果。然而,由于肿瘤的免疫抑制环境和转运障碍,在 OC 中只有 15%的检查点抑制剂被证明是成功的。这限制了现有免疫疗法的疗效。基于纳米技术的递药系统有潜力克服这些限制。各种纳米制剂,包括聚合物、脂质体和脂质-聚合物杂化纳米粒子,已经被提出用于改善针对肿瘤相关免疫细胞(包括树突状细胞和巨噬细胞)的药物的生物分布和靶向能力。在这篇综述中,我们研究了目前正在考虑用于治疗 OC 的免疫治疗方法的影响。在这篇综述中,我们还全面分析了现有的基于纳米粒子的合成策略及其与标准治疗相比的局限性和优势。此外,我们还讨论了纳米技术与免疫疗法的结合如何有助于克服其单独应用相关的当前治疗局限性,并为这种恶性肿瘤的治疗开辟一个新的范例。

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