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基于靶向纳米载体的药物传递策略提高 PARP 抑制剂治疗卵巢癌的疗效。

Targeted Nanocarrier-Based Drug Delivery Strategies for Improving the Therapeutic Efficacy of PARP Inhibitors against Ovarian Cancer.

机构信息

Department of Medical Biophysics, Institute of Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland.

出版信息

Int J Mol Sci. 2024 Jul 30;25(15):8304. doi: 10.3390/ijms25158304.

Abstract

The current focus of ovarian cancer (OC) research is the improvement of treatment options through maximising drug effectiveness. OC remains the fifth leading cause of cancer-induced mortality in women worldwide. In recent years, nanotechnology has revolutionised drug delivery systems. Nanoparticles may be utilised as carriers in gene therapy or to overcome the problem of drug resistance in tumours by limiting the number of free drugs in circulation and thereby minimising undesired adverse effects. Cell surface receptors, such as human epidermal growth factor 2 (HER2), folic acid (FA) receptors, CD44 (also referred to as homing cell adhesion molecule, HCAM), and vascular endothelial growth factor (VEGF) are highly expressed in ovarian cancer cells. Generation of active targeting nanoparticles involves modification with ligands that recognise cell surface receptors and thereby promote internalisation by cancer cells. Several poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi) are currently used for the treatment of high-grade serous ovarian carcinomas (HGSOC) or platinum-sensitive relapsed OC. However, PARP resistance and poor drug bioavailability are common challenges, highlighting the urgent need to develop novel, effective strategies for ovarian cancer treatment. This review evaluates the utility of nanoparticles in ovarian cancer therapy, with a specific focus on targeted approaches and the use of PARPi nanocarriers to optimise treatment outcomes.

摘要

目前,卵巢癌(OC)研究的重点是通过最大限度地提高药物疗效来改善治疗方案。OC 仍然是全球女性癌症相关死亡的第五大主要原因。近年来,纳米技术彻底改变了药物传递系统。纳米粒子可用作基因治疗的载体,或通过限制循环中游离药物的数量来克服肿瘤的耐药性问题,从而最大限度地减少不良的不良反应。细胞表面受体,如人类表皮生长因子 2(HER2)、叶酸(FA)受体、CD44(也称为归巢细胞黏附分子,HCAM)和血管内皮生长因子(VEGF)在卵巢癌细胞中高度表达。主动靶向纳米粒子的产生涉及与识别细胞表面受体的配体的修饰,从而促进癌细胞的内化。目前有几种多聚(ADP-核糖)聚合酶(PARP)抑制剂(PARPi)用于治疗高级别浆液性卵巢癌(HGSOC)或铂类敏感复发性 OC。然而,PARP 耐药性和药物生物利用度差是常见的挑战,这凸显了迫切需要开发治疗卵巢癌的新的、有效的策略。本文综述了纳米粒子在卵巢癌治疗中的应用,特别关注了靶向方法和 PARPi 纳米载体的使用,以优化治疗效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b587/11312858/506e8c90e212/ijms-25-08304-g001.jpg

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