Department of Pharmaceutical Sciences, Shalom Institute of Health & Allied Sciences, Sam Higginbottom University of Agriculture, Technology & Sciences , Allahabad, India.
Department of Pharmacology, College of Pharmacy, Jouf University , Sakakah, Saudi Arabia.
Expert Opin Drug Deliv. 2020 Jun;17(6):805-816. doi: 10.1080/17425247.2020.1757645. Epub 2020 May 6.
Since decades, cancer is a major public health problem worldwide. The increasing knowledge of molecular and tumor biology has significantly changed the cancer treatment paradigms during the past few years.
Conventionally, the first-line treatment of solid tumors is their surgical removal followed by chemotherapy and/or radiation treatment. Unfortunately, these approaches often fail, and the patient may discontinue the treatment before the complete eradication of tumors due to therapeutic and toxicological limitations. In this regard, the nucleic acid-based treatment therapy has been widely used in the management of cancer. However, nucleic acid delivery to the target sites is highly challenging because of their molecular size, difficulties to pass cellular membranes, and susceptibility toward enzymatic and/or chemical degradation.
Researchers have now overcome many problems associated with delivering nucleic acids to the target tissues by preventing them from off-target side effects and overcoming rapid degradation and clearance in the bloodstream using the lipid-polymer hybrid nanoparticles (LPHNs). The present review, therefore, aims to provide an overview account on LPNHs, their preparation, characterization, application with special emphasis on intracellular delivery/transfection of nucleic acids in the management of cancer, and key aspects of challenges in its delivery and clinical transition.
几十年来,癌症一直是全球主要的公共卫生问题。近年来,分子和肿瘤生物学知识的不断增加,极大地改变了癌症治疗模式。
传统上,实体瘤的一线治疗方法是手术切除,然后进行化疗和/或放疗。不幸的是,由于治疗和毒理学的限制,这些方法往往会失败,患者可能在肿瘤完全清除之前就停止治疗。在这方面,基于核酸的治疗方法已广泛应用于癌症的治疗。然而,由于核酸的分子尺寸较大、难以穿透细胞膜,以及易受到酶和/或化学降解的影响,将核酸递送到靶部位极具挑战性。
研究人员现在已经通过使用脂质-聚合物杂合纳米粒子(LPHN)来防止核酸产生脱靶副作用,并克服其在血液中快速降解和清除的问题,从而克服了将核酸递送到靶组织的许多相关问题。因此,本综述旨在概述 LPHN,及其制备、表征、应用,特别强调其在癌症管理中核酸的细胞内递/转染,以及其递送和临床转化中的关键挑战方面。