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

•The PEG-g-PEI and folic acid grafted PDA nanoplatform has good stability and photothermal conversion efficiency.•The nanocomposites internalize more miR-21i into cancer cells by FR-mediated endocytosis and help lysosome escape of miR-21i.•The nanocomposites inhibit proliferation and induce apoptosis of breast cancer cells under photothermal and gene therapies.•The nanocomposites showed in vivo satisfactory tumor growth inhibition effects under photothermal and gene therapies. 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.