Functionalized PAMAM-Based system for targeted delivery of miR-205 and 5-fluorouracil in breast cancer

Abstract

Chemotherapy combined with gene therapy is a promising treatment strategy for breast cancer. However, nonspecific bio-distribution and lack of targeting ability are major challenge for breast cancer therapy. Herein, we investigated whether the anticancer drug 5-fluorouracil (5-FU) and miR-205 could be co-delivered by functionalized PAMAM to the breast cancer cells and realize enhanced therapeutic efficacy relative to mono-treatment. The fifth-poly(amidoamine) (PAMAM) functionalized with human luteinizing hormone releasing hormone (LHRH) and the acetic anhydride was designed as a drug and gene carrier, providing reduced toxicity of the PAMAM and improving the targeting properties of drugs during delivery. The functionalized PAMAM-based 5-FU and miR-205 co-delivery system (LHRH-G5.0NHAC-FUA/miR-205) was fabricated through an amide condensation reaction and an electrostatic self-assembly. Size, zeta potential and the drug loading of the developed co-delivery system were 238.4 ± 2.3 nm, 4.40 ± 0.23 mV and 40.76%, respectively. Cytotoxicity studies showed a greater antiproliferation effect of LHRH-G5.0NHAC-FUA/miR-205 than its nontargeted counterpart. In vivo studies exhibited a higher antitumor efficiency of LHRH-G5.0NHAC-FUA/miR-205 than its nontargeted counterpart. Therefore, the developed co-delivery system is a promising platform for the efficient co-delivery of miR-205 and 5-FU and shows good anti-breast cancer effect.