Enhanced Chemotherapeutic Efficacy of Paclitaxel Nanoparticles Co-delivered with MicroRNA-7 by Inhibiting Paclitaxel-Induced EGFR/ERK pathway Activation for Ovarian Cancer Therapy

• DOI: 10.1021/acsami.7b19183
• Publication Date: 2018-02-07T14:09:03Z
• Authors: Xiaojuan Cui; Ying Sun; Ming Shen; Keqi Song; Xia Yin; Wen Di; Yourong Duan
• Keywords: Ovarian Neoplasms; 0301 basic medicine; 2. Zero hunger; Paclitaxel; MAP Kinase Signaling System; 02 engineering and technology; Antineoplastic Agents, Phytogenic; 3. Good health; ErbB Receptors; MicroRNAs; 03 medical and health sciences; Cell Line, Tumor; Humans; Nanoparticles; Female; Extracellular Signal-Regulated MAP Kinases; 0210 nano-technology

Chemotherapy-induced activation of cell survival pathways leads to drug resistance. MicroRNAs (miRNAs) post-transcriptionally regulate gene expression in many biological pathways. Paclitaxel (PTX) is one the first-line chemotherapy drugs for ovarian cancer, and it induces epidermal growth factor receptor (EGFR)/extracellular signal-regulated kinase (ERK) pathway that tumor proliferation, survival, invasion, MicroRNA-7 (miR-7) has ability suppress EGFR/ERK pathway. To sensitize chemotherapy, we developed monomethoxy(poly(ethylene glycol))–poly(d,l-lactide-co-glycolide)–poly(l-lysine) nanoparticles simultaneous co-delivery PTX miR-7. The resulting PTX/miR-7 (P/MNPs) protect miRNA from degradation, possess a sequential controlled release drugs, improve transfection efficiency miRNA, decrease half-maximal inhibitory concentration PTX, increase apoptosis cancer cells. chemotherapeutic efficacy prominently enhanced vitro vivo via inhibition PTX-induced by Our studies P/MNPs reveal novel paradigm dual-drug-delivery system chemotherapeutics therapy treating cancers.