Department of Physiology and Pathophysiology, School of Basic Medicine, Qingdao University, QingDao, ShanDong 266071, PR China; Department of Biochemistry and Molecular Biology, Binzhou Medical University, YanTai, ShanDong 264003, PR China.
School of International Studies, Binzhou Medical University, YanTai, ShanDong 264003, PR China.
J Control Release. 2021 Aug 10;336:396-409. doi: 10.1016/j.jconrel.2021.06.034. Epub 2021 Jun 25.
The emergence of multidrug resistance (MDR) in malignant tumors is the primary reason for invalid chemotherapy. Antitumor drugs are often adversely affected by the MDR of tumor cells. Treatments using conventional drugs, which have specific drug targets, hardly regulate the complex signaling pathway of MDR cells because of the complex formation mechanism of MDR. However, natural products have positive advantages, such as high efficiency, low toxicity, and ability to target multiple mechanism pathways associated with MDR. Natural products, as MDR reversal agents, synergize with chemotherapeutics and enhance the sensitivity of tumor cells to chemotherapeutics, and the co-delivery of natural products and antitumor drugs with nanocarriers maximizes the synergistic effects against MDR in tumor cells. This review summarizes the molecular mechanisms of MDR, the advantages of natural products combined with chemotherapeutics in offsetting complicated MDR mechanisms, and the types and mechanisms of natural products that are potential MDR reversal modulators. Meanwhile, aiming at the low bioavailability of cocktail combined natural products and chemotherapeutic in vivo, the advantages of nanoplatform-based co-delivery system and recent research developments are illustrated on the basis of our previous research. Finally, prospective horizons are analyzed, which are expected to considerably improve the nano-co-delivery of natural products and chemotherapeutic systems for MDR reversal in cancer.
多药耐药（MDR）的出现是恶性肿瘤化疗无效的主要原因。抗肿瘤药物常因肿瘤细胞 MDR 的复杂形成机制而受到影响，常规药物的治疗作用具有特定的药物靶点，难以调节 MDR 细胞的复杂信号通路。然而，天然产物具有高效、低毒、能靶向与 MDR 相关的多个机制途径等积极优势。天然产物作为 MDR 逆转剂，与化疗药物协同作用，增强肿瘤细胞对化疗药物的敏感性，纳米载体共载天然产物和抗肿瘤药物可最大限度地发挥对肿瘤细胞 MDR 的协同作用。本文综述了 MDR 的分子机制，天然产物与化疗药物联合应用克服复杂 MDR 机制的优势，以及天然产物作为潜在 MDR 逆转调节剂的类型和作用机制。同时，针对鸡尾酒联合天然产物和化疗药物体内生物利用度低的问题，基于我们以前的研究，阐述了基于纳米平台的共递药系统的优势和最新研究进展。最后，分析了预期的前景，有望显著改善天然产物和化疗药物的纳米共递药系统，从而逆转癌症的 MDR。
