School of Pharmacy and Pharmaceutical Sciences & Institute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, People's Republic of China.
NHC Key Laboratory of Biotechnology Drugs (Shandong Academy of Medical Sciences), Jinan, Shandong, 250117, People's Republic of China.
Int J Nanomedicine. 2023 Apr 12;18:1965-1987. doi: 10.2147/IJN.S394383. eCollection 2023.
Ovarian cancer is one of the most common malignant tumors in gynecology with a high incidence. Combination therapy, eg, administration of paclitaxel followed by a platinum anticancer drug is recommended to treat ovarian cancer due to its advantages in, eg, reducing side effects and reversing (multi)drug-resistance compared to single treatment. However, the benefits of combination therapy are often compromised. In chemo and chemo/gene combinations, co-deposition of the combined therapeutics in the tumor cells is required, which is difficult to achieve due to dramatic pharmacokinetic differences between combinational agents in free forms. Moreover, some undesired properties such as the low-water solubility of chemodrugs and the difficulty of cellular internalization of gene therapeutics also hinder the therapeutic potential. Delivery of dual or multiple agents by nanoparticles provides opportunities to tackle these limits. Nanoparticles encapsulate hydrophobic drug(s) to yield aqueous dispersions facilitating its administration and/or to accommodate hydrophilic genes facilitating its access to cells. Moreover, nanoparticle-based therapeutics can not only improve drug properties (eg, in vivo stability) and ensure the same drug disposition behavior with controlled drug ratios but also can minimize drug exposure of the normal tissues and increase drug co-accumulation at targeted tissues via passive and/or active targeting strategies. Herein, this work summarizes nanoparticle-based combination therapies, mainly including anticancer drug-based combinations and chemo/gene combinations, and emphasizes the advantageous outcomes of nanocarriers in the combination treatment of ovarian cancer. In addition, we also review mechanisms of synergetic effects resulting from different combinations.
卵巢癌是妇科最常见的恶性肿瘤之一，发病率较高。由于联合治疗在减少副作用和逆转（多）药物耐药性方面优于单一治疗，因此推荐使用紫杉醇联合铂类抗癌药物进行治疗。然而，联合治疗的益处往往受到影响。在化疗和化疗/基因联合治疗中，需要联合治疗在肿瘤细胞中共同沉积，但由于游离形式的组合药物之间存在显著的药代动力学差异，因此难以实现。此外，一些不理想的性质，如化疗药物的低水溶性和基因治疗剂的细胞内化困难，也阻碍了治疗潜力。纳米粒子的双重或多重药物输送提供了克服这些限制的机会。纳米粒子将疏水性药物包裹起来，形成水基分散体，便于给药和/或容纳亲水性基因，便于其进入细胞。此外，基于纳米粒子的治疗剂不仅可以改善药物性质（例如体内稳定性），确保相同的药物分布行为和受控的药物比例，还可以通过被动和/或主动靶向策略最小化正常组织的药物暴露，并增加靶向组织的药物共同积累。本文总结了基于纳米粒子的联合治疗，主要包括基于抗癌药物的联合治疗和化疗/基因联合治疗，并强调了纳米载体在卵巢癌联合治疗中的优势。此外，我们还回顾了不同组合产生协同效应的机制。
