Irma Lerma Rangel College of Pharmacy, Texas A&M Health Science Center, Kingsville, TX 78363, USA.
Expert Opin Drug Deliv. 2012 Mar;9(3):287-301. doi: 10.1517/17425247.2012.665365.
Resistance to chemotherapy is a major obstacle in the successful amelioration of tumors in many cancer patients. Resistance is either intrinsic or acquired, involving mechanisms such as genetic aberrations, decreased influx and increased efflux of drugs. Strategies for the reversal of resistance involve the alteration of enzymes responsible for drug resistance, the modulation of proteins regulating apoptosis mechanisms and improving the uptake of drugs using nanotechnology. Novel strides in the reversal of drug resistance are emerging, involving the use of nanotechnology, targeting stem cells, etc.
This paper reviews the most recent cancer drug reversal strategies involving nanotechnology for targeting cancer cells and cancer stem cells (CSCs), for enhanced uptake of micro- and macromolecular inhibitors.
Nanotechnology used in conjunction with existing therapies, such as gene therapy and P-glycoprotein inhibition, has been shown to improve the reversal of drug resistance; the mechanisms involved in this include specific targeting of drugs and nucleotide therapeutics, enhanced cellular uptake of drugs and improved bioavailability of drugs with poor physicochemical characteristics. Important strategies in the reversal of drug resistance include: a multifunctional nanoparticulate system housing a targeting moiety; therapeutics to kill resistant cancer cells and CSCs; cytotoxic drugs and a tumor microenvironment stimuli-responsive element, to release the encapsulated therapeutics.
化疗耐药性是许多癌症患者成功改善肿瘤的主要障碍。耐药性要么是内在的,要么是获得性的,涉及到基因异常、药物流入减少和流出增加等机制。逆转耐药性的策略包括改变负责耐药性的酶、调节调节细胞凋亡机制的蛋白质以及利用纳米技术提高药物摄取。逆转耐药性的新进展正在出现,涉及利用纳米技术靶向干细胞等。
本文综述了最新的癌症药物逆转策略,涉及纳米技术靶向癌细胞和癌症干细胞(CSC),以增强对小分子和大分子抑制剂的摄取。
纳米技术与现有疗法(如基因治疗和 P-糖蛋白抑制)联合使用已被证明可以改善耐药性的逆转;涉及的机制包括药物和核苷酸治疗的特异性靶向、药物的细胞摄取增强以及改善物理化学性质差的药物的生物利用度。逆转耐药性的重要策略包括:一个多功能纳米颗粒系统,其中包含一个靶向部分;杀死耐药癌细胞和 CSC 的治疗方法;细胞毒性药物和肿瘤微环境刺激反应元件,以释放封装的治疗药物。