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用于寻找癌症治疗途径的蛋白质及其功能化:现状与未来展望。

Proteins and their functionalization for finding therapeutic avenues in cancer: Current status and future prospective.

作者信息

Mohanty Sonali, Panda Sikta, Devadharshini U, Paul Subhankar

机构信息

Department of Biotechnology & Medical Engineering, National Institute of Technology Rourkela, Rourkela 769008, Odisha, India.

Department of Mechanical Engineering, National Institute of Technology Rourkela, Rourkela, 769008, Odisha, India.

出版信息

Biochim Biophys Acta Rev Cancer. 2023 Mar;1878(2):188862. doi: 10.1016/j.bbcan.2023.188862. Epub 2023 Feb 13.

Abstract

Despite the remarkable advancement in the health care sector, cancer remains the second most fatal disease globally. The existing conventional cancer treatments primarily include chemotherapy, which has been associated with little to severe side effects, and radiotherapy, which is usually expensive. To overcome these problems, target-specific nanocarriers have been explored for delivering chemo drugs. However, recent reports on using a few proteins having anticancer activity and further use of them as drug carriers have generated tremendous attention for furthering the research towards cancer therapy. Biomolecules, especially proteins, have emerged as suitable alternatives in cancer treatment due to multiple favourable properties including biocompatibility, biodegradability, and structural flexibility for easy surface functionalization. Several in vitro and in vivo studies have reported that various proteins derived from animal, plant, and bacterial species, demonstrated strong cytotoxic and antiproliferative properties against malignant cells in native and their different structural conformations. Moreover, surface tunable properties of these proteins help to bind a range of anticancer drugs and target ligands, thus making them efficient delivery agents in cancer therapy. Here, we discuss various proteins obtained from common exogenous sources and how they transform into effective anticancer agents. We also comprehensively discuss the tumor-killing mechanisms of different dietary proteins such as bovine α-lactalbumin, hen egg-white lysozyme, and their conjugates. We also articulate how protein nanostructures can be used as carriers for delivering cancer drugs and theranostics, and strategies to be adopted for improving their in vivo delivery and targeting. We further discuss the FDA-approved protein-based anticancer formulations along with those in different phases of clinical trials.

摘要

尽管医疗保健领域取得了显著进展,但癌症仍是全球第二大致命疾病。现有的传统癌症治疗方法主要包括化疗(其副作用从轻微到严重不等)和放疗(通常费用高昂)。为了克服这些问题,人们探索了靶向特异性纳米载体来递送化疗药物。然而,最近关于使用一些具有抗癌活性的蛋白质并将其进一步用作药物载体的报道,引发了人们对推进癌症治疗研究的极大关注。生物分子,尤其是蛋白质,由于具有生物相容性、可生物降解性以及易于表面功能化的结构灵活性等多种有利特性,已成为癌症治疗中合适的替代物。多项体外和体内研究报告称,源自动物、植物和细菌物种的各种蛋白质,在天然状态及其不同结构构象下,对恶性细胞均表现出强大的细胞毒性和抗增殖特性。此外,这些蛋白质的表面可调谐特性有助于结合一系列抗癌药物和靶向配体,从而使其成为癌症治疗中高效的递送剂。在此,我们讨论从常见外源获得的各种蛋白质,以及它们如何转化为有效的抗癌剂。我们还全面讨论了不同膳食蛋白质(如牛α-乳白蛋白、鸡蛋清溶菌酶及其缀合物)的肿瘤杀伤机制。我们还阐述了蛋白质纳米结构如何用作递送癌症药物和治疗诊断剂的载体,以及为改善其体内递送和靶向性而应采用的策略。我们进一步讨论了美国食品药品监督管理局(FDA)批准的基于蛋白质的抗癌制剂以及处于不同临床试验阶段的制剂。

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