Liu Yarong, Fang Jinxu, Joo Kye-Il, Wong Michael K, Wang Pin
Mork Family Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, California, United States of America.
Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
PLoS One. 2014 Oct 17;9(10):e110611. doi: 10.1371/journal.pone.0110611. eCollection 2014.
Multidrug resistance (MDR) is a significant challenge to effective cancer chemotherapy treatment. However, the development of a drug delivery system that allows for the sustained release of combined drugs with improved vesicle stability could overcome MDR in cancer cells. To achieve this, we have demonstrated codelivery of doxorubicin (Dox) and paclitaxel (PTX) via a crosslinked multilamellar vesicle (cMLV). This combinatorial delivery system achieves enhanced drug accumulation and retention, in turn resulting in improved cytotoxicity against tumor cells, including drug-resistant cells. Moreover, this delivery approach significantly overcomes MDR by reducing the expression of P-glycoprotein (P-gp) in cancer cells, thus improving antitumor activity in vivo. Thus, by enhancing drug delivery to tumors and lowering the apoptotic threshold of individual drugs, this combinatorial delivery system represents a potentially promising multimodal therapeutic strategy to overcome MDR in cancer therapy.
多药耐药性（MDR）是有效癌症化疗治疗面临的重大挑战。然而，开发一种能够实现联合药物持续释放且囊泡稳定性提高的药物递送系统，可以克服癌细胞中的多药耐药性。为实现这一目标，我们已证明通过交联多层囊泡（cMLV）实现阿霉素（Dox）和紫杉醇（PTX）的共递送。这种组合递送系统实现了增强的药物积累和滞留，进而提高了对肿瘤细胞（包括耐药细胞）的细胞毒性。此外，这种递送方法通过降低癌细胞中P-糖蛋白（P-gp）的表达，显著克服了多药耐药性，从而提高了体内抗肿瘤活性。因此，通过增强药物向肿瘤的递送并降低单个药物的凋亡阈值，这种组合递送系统代表了一种在癌症治疗中克服多药耐药性的潜在有前景的多模式治疗策略。
