Zhang Xiaoyang, Liu Yarong, Kim Yu Jeong, Mac John, Zhuang Rachel, Wang Pin
Mork Family Department of Chemical Engineering and Materials Science , University of Southern California , 3710 McClintock Ave. , RTH509 , Los Angeles , CA 90089 , USA . Email:
Department of Pharmacology and Pharmaceutical Sciences , University of Southern California , Los Angeles , CA 90089 , USA.
RSC Adv. 2017 Apr 3;7(32):19685-19693. doi: 10.1039/c7ra01100h.
Carboplatin (CPT) and paclitaxel (PTX) used in combination is one of the most effective treatments for ovarian cancer. However, the traditional combination methods used to co-administrate CPT and PTX showed limited clinical efficacy due to their distinct pharmacokinetics. Although much effort has been devoted to developing nanoparticles capable of encapsulating drugs with different lipophilicites, co-delivery of carboplatin with paclitaxel by a single nanoparticle has rarely been reported. Here, we encapsulated and delivered this drug combination to ovarian cancer cells at a controlled ratio by a previously reported crosslinked multilamellar liposome vesicle (cMLV). A 1 : 1 CPT/PTX molar ratio for cMLVs (CPT/PTX) combination treatment was found to induce the strongest anti-tumor synergism and to target ALDH+ cancer stem cells (CSC) . Moreover, we demonstrated that this co-encapsulation strategy reduced systemic cytotoxicity and resulted in a stronger anti-tumor effect when compared to free drug combinations and individual drug-loaded cMLVs in an OVCAR8 ovarian cancer xenograft mouse model. Thus, this study suggests a potentially promising combination therapy for ovarian cancer in clinical practice.
卡铂（CPT）与紫杉醇（PTX）联合使用是卵巢癌最有效的治疗方法之一。然而，由于其不同的药代动力学特性，用于同时给予CPT和PTX的传统联合方法临床疗效有限。尽管人们致力于开发能够包封不同亲脂性药物的纳米颗粒，但很少有关于通过单个纳米颗粒同时递送卡铂和紫杉醇的报道。在此，我们通过先前报道的交联多层脂质体囊泡（cMLV）以可控比例将这种药物组合包封并递送至卵巢癌细胞。发现cMLV（CPT/PTX）组合治疗的1:1 CPT/PTX摩尔比可诱导最强的抗肿瘤协同作用，并靶向ALDH+癌症干细胞（CSC）。此外，我们证明，与游离药物组合和OVCAR8卵巢癌异种移植小鼠模型中的单个载药cMLV相比，这种共包封策略降低了全身细胞毒性，并产生了更强的抗肿瘤作用。因此，本研究提示了一种在临床实践中对卵巢癌具有潜在前景的联合治疗方法。
