Co-delivery of Cisplatin and Rapamycin for Enhanced Anticancer Therapy through Synergistic Effects and Microenvironment Modulation

• DOI: 10.1021/nn5010815
• Publication Date: 2014-04-10T16:37:34Z
• Authors: Shutao Guo; C. Michael Lin; Zhenghong Xu; Lei Miao; Yuhua Wang; Leaf Huang
• Keywords: PLGA

The tumor microenvironment plays an important role in the tumor's progression and metastasis. Therefore, successful alteration of this delicate setting against favor can open a window for therapeutic efficacy. We have developed modality to bring about treatment-induced alterations by employing synergistic effects between two drugs. Co-delivery rapamycin (RAPA), mTOR inhibitor that may offer notable therapy through antiangiogenic activity, alongside cisplatin foster significant potency as RAPA sensitizes A375 melanoma cells modulation. However, encapsulation these drugs into poly(lactic-co-glycolic acid) (PLGA) NPs was inefficient due incompatibility free polymer matrix. Here, we show be made hydrophobic coating nanoprecipitate (cores) drug with dioleoylphosphatidic acid (DOPA). These DOPA coated cores are compatible PLGA coencapsulated at molar ratio promote antitumor activity. presence significantly improved NPs. Furthermore, containing both induced apoptosis on A375-luc human vitro. Additionally, they inhibited growth xenograft model modulation vasculature permitted enhanced penetration tumor.