Beretta Giovanni L, Cavalieri Francesca
Dipartimento di Scienze e Tecnologie Chimiche Università di Roma Tor Vergata, Via della ricerca scientifica 1 00173, Roma, Italy.
Curr Med Chem. 2016;23(1):3-22. doi: 10.2174/0929867322666151006094559.
Drug resistance to conventional antitumor drugs represents one of the major causes of treatment failure in patients affected by tumors. Two main types of drug resistance to anticancer drugs are found in tumors, namely intrinsic resistance, in which tumor cells are inherently resistant to chemotherapy, and acquired resistance, which results from previous drug exposure. Tumor cells resistant to a chemotherapeutic agent become cross-resistant to both similar and structurally unrelated classes of antitumor drugs, a biological mechanism known as multi drug resistance (MDR). Among the strategies considered to overcome MDR, nanovector-mediated drug administration represents an innovative and promising alternative. In this review, we report a number of nanovectors including polymer-drug conjugates, polymeric micelles, nanotubes, LbL nanocapsules, and silica and gold nanoparticles. These systems are designed for the efficient delivery of anthracyclines, vinca alkaloids, taxanes, and others drugs. The development of these nanovectos to specifically overcome MDR and their mechanisms of action are covered and discussed. Finally, we discuss challenges and opportunities for further development of nanodevices-based chemotherapies to circumvent MDR through the design of nanovectors for the delivery of multiple cargoes.
对传统抗肿瘤药物的耐药性是肿瘤患者治疗失败的主要原因之一。肿瘤中发现的抗癌药物耐药性主要有两种类型，即内在耐药性，肿瘤细胞对化疗天然耐药；以及获得性耐药，这是先前药物暴露导致的结果。对化疗药物耐药的肿瘤细胞会对相似和结构不相关的各类抗肿瘤药物产生交叉耐药，这种生物学机制称为多药耐药（MDR）。在被认为可克服多药耐药的策略中，纳米载体介导的药物给药是一种创新且有前景的选择。在本综述中，我们报告了多种纳米载体，包括聚合物 - 药物偶联物、聚合物胶束、纳米管、层层组装纳米胶囊以及二氧化硅和金纳米颗粒。这些系统旨在高效递送蒽环类药物、长春花生物碱、紫杉烷类及其他药物。本文涵盖并讨论了这些纳米载体专门用于克服多药耐药的研发情况及其作用机制。最后，我们讨论了基于纳米装置的化疗进一步发展所面临的挑战和机遇，即通过设计用于递送多种药物的纳米载体来规避多药耐药。
