Tumor-targeting gene-photothermal synergistic therapies based on multifunctional polydopamine nanoparticles

Abstract

Gene-photothermal synergistic therapy shows great potential for breast cancer treatment. Polydopamine (PDA) is a widely used photothermal therapeutic agent and delivery vector. Herein, a tumor-targeted nanoplatform of PDA grafted with PEG-g-PEI and folic acid (FA) (PPF) was elaborately fabricated for precisely intracellular delivery of microRNA-21 inhibitor (miR-21i). The multifunctional nanoplatform possessed a narrow size distribution, good stability, and excellent photothermal conversion efficiency. In vitro FA modification more effectively promoted the intracellular uptake of the nanocomposites by MCF-7 and 4T1 cells, and facilitated the miR-21i escape from the lysosomes, thus significantly inhibiting cell proliferation and inducing tumor cell apoptosis. More importantly, in vivo satisfactory tumor growth inhibition effects were observed in PPF/miR21 and laser co-treated group due to the near-infrared (NIR) responsive PDA and conjugated tumor-targeting FA. In conclusion, this nanocarrier delivery system exhibit enhanced anti-cancer effect, indicating the outstanding advantages of synergistic therapy by intergrating photothermal, gene, and accurate cancer-targeted treatment into one system, which will provide a valuable strategy for the clinical treatment of breast cancer.