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新型细胞外囊泡工程方法提高抗癌疗法疗效。

New approaches in extracellular vesicle engineering for improving the efficacy of anti-cancer therapies.

机构信息

Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Institute for Digital Medicine, Immunology Programme and Cancer Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; N.1 Institute for Health, National University of Singapore, Singapore; Department of Biomedical Sciences, College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Hong Kong.

Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Institute for Digital Medicine, Immunology Programme and Cancer Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; N.1 Institute for Health, National University of Singapore, Singapore.

出版信息

Semin Cancer Biol. 2021 Sep;74:62-78. doi: 10.1016/j.semcancer.2021.02.010. Epub 2021 Feb 17.

DOI:10.1016/j.semcancer.2021.02.010
PMID:33609665
Abstract

Cancer is a disease that evolves continuously with unpredictable outcomes. Although conventional chemotherapy can display significant antitumor effects, the lack of specificity and poor bioavailability remain major concerns in cancer therapy. Moreover, with the advent of novel anti-cancer gene therapies, there is an urgent need for drug delivery vectors capable of bypassing cellular barriers and efficiently transferring therapeutic cargo to recipient cells. A number of drug delivery systems have been proposed to overcome these limitations, but their successful clinical translation has been hampered by the onset of unexpected side effects and associated toxicities. The application of extracellular vesicles (EVs), a class of naturally released, cell-derived particles, as drug delivery vectors presents a breakthrough in nanomedicine, taking into account their biocompatibility and natural role in intercellular communication. Combining the advantageous intrinsic properties of EVs with surface functionalization and the encapsulation of drugs allows for a new class of engineered EVs that serve as effective therapeutic carriers. Here, we describe the various successful approaches involving the application of engineered EVs as bio-derived drug delivery vectors in cancer therapy. The latest and most effective strategies of engineering EVs to improve drug loading, stealth properties and tumour targeting capabilities of EVs are debated. Finally, current obstacles and future perspectives of smart engineered EVs are discussed.

摘要

癌症是一种不断演变的疾病,其结果难以预测。尽管传统的化疗可以显示出显著的抗肿瘤效果,但缺乏特异性和较差的生物利用度仍然是癌症治疗中的主要关注点。此外,随着新型抗癌基因治疗方法的出现,迫切需要能够绕过细胞屏障并将治疗货物有效递送至靶细胞的药物递送载体。已经提出了许多药物递送系统来克服这些限制,但它们的成功临床转化受到意外副作用和相关毒性的影响。细胞外囊泡(EVs)作为药物递送载体的应用是纳米医学的一个突破,考虑到它们的生物相容性和在细胞间通讯中的天然作用。将 EVs 的有利固有特性与表面功能化和药物包封结合起来,可以产生一类新的工程 EVs,作为有效的治疗载体。在这里,我们描述了涉及将工程 EVs 作为生物衍生的药物递送载体应用于癌症治疗的各种成功方法。讨论了最新和最有效的工程 EVs 策略,以提高 EVs 的药物装载、隐形特性和肿瘤靶向能力。最后,讨论了智能工程 EVs 的当前障碍和未来前景。

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