Ashfaq Usman Ali, Riaz Muhammad, Yasmeen Erum, Yousaf Muhammad Zubair
Department of Bioinformatics & Biotechnology, Government College University, 38000 Faisalabad, Pakistan.
Government College University, 38000 Faisalabad, Pakistan; National Centre for Bioinformatics, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan.
Crit Rev Ther Drug Carrier Syst. 2017;34(4):317-353. doi: 10.1615/CritRevTherDrugCarrierSyst.2017017845.
Cancer is one of the major causes of death worldwide. The silent activation of cellular factors responsible for deviation from normal regulatory pathways leads to the development of cancer. Nano-biotechnology is a novel drug-delivery system with high potential of efficacy and accuracy to target lethal cancers. Various biocompatible nanoparticle (NP)-based drug-delivery systems such as liposomes, dendrimers, micelles, silica, quantum dots, and magnetic, gold, and carbon nanotubes have already been reported for successful targeted cancer treatment. NPs are functionalized with different biological molecules, peptides, antibody, and protein ligands for targeted drug delivery. These systems include a hydrophilic central core, a target-oriented biocompatible outer layer, and a middle hydrophobic core where the drug destined to reach target site resides. Most of the NPs have the ability to maintain their structural shape and are constructed according to the cancer microenvironment. The self-assembling and colloidal properties of NPs have caused them to become the best vehicles for targeted drug delivery. The tumor microenvironment (TME) plays a major role in cancer progression, detection, and treatment. Due to its continuous complex behavior, the TME can hinder delivery systems, thus halting cancer treatment. Nonetheless, a successful biophysiological interaction between the NPs and the TME results in targeted release of drugs. Currently, a number of drugs and NP-based delivery systems against cancer are in clinical and preclinical trials and a few have been approved by Food and Drug Administration (FDA); for example: taxol, doxil, cerubidine, and adrucil. This review summarizes topical advances about the drugs being used for cancer treatment, their targeted delivery systems based on NPs, and the role of TME in this connection.
癌症是全球主要死因之一。负责偏离正常调节途径的细胞因子的沉默激活会导致癌症的发展。纳米生物技术是一种新型药物递送系统,在靶向治疗致命癌症方面具有高效和精准的巨大潜力。各种基于生物相容性纳米颗粒(NP)的药物递送系统,如脂质体、树枝状大分子、胶束、二氧化硅、量子点以及磁性、金和碳纳米管,已被报道用于成功的靶向癌症治疗。NP通过不同的生物分子、肽、抗体和蛋白质配体进行功能化,以实现靶向药物递送。这些系统包括一个亲水性中心核、一个面向靶标的生物相容性外层以及一个中间疏水性核,其中预定到达靶位点的药物位于该疏水性核中。大多数NP能够保持其结构形状,并根据癌症微环境构建。NP的自组装和胶体性质使其成为靶向药物递送的最佳载体。肿瘤微环境(TME)在癌症进展、检测和治疗中起主要作用。由于其持续复杂的行为,TME会阻碍递送系统,从而使癌症治疗停滞不前。尽管如此,NP与TME之间成功的生物生理相互作用会导致药物的靶向释放。目前,许多抗癌药物和基于NP的递送系统正处于临床和临床前试验阶段,并且有一些已获得美国食品药品监督管理局(FDA)的批准;例如:紫杉醇、多柔比星脂质体、柔红霉素和氟尿嘧啶。本综述总结了用于癌症治疗的药物、基于NP的靶向递送系统以及TME在这方面的作用的最新进展。