Fabrication of targeted PDA-Hemin-Dox-FA nanoplatform for enhanced chemodynamic therapy synergized with chemo/photothermal therapy

Abstract

Chemotherapy (CT) is widely used in clinical practice due to its simple and convenient steps, but its characteristics of systemic administration also results in a lack of targeting and a tendency to develop drug resistance, which greatly limits its therapeutic effect. In order to overcome these problems, a PDA-Hemin-Dox-FA (PHDF) nanoplatform was constructed in this work for the combined treatment of tumors. Firstly, hemin was introduced into the self-polymerization of dopamine to synthesize PDA-Hmein (PH) nanoparticles. Then, the chemotherapy drug doxorubicin (Dox) and targeted folic acid (FA) were loaded onto PH surfaces through Schiff base and amide bonds respectively to construct PHDF. When PHDF enters the tumor cells through the targeting guidance of FA, the acidic microenvironment of the tumor will induce the cleavage of the Schiff base bond in PHDF to release Dox. The presence of hemin makes PHDF have high Fenton-like activity, which generate large amount of·OH to perform chemodynamic therapy (CDT). Driven by near infrared laser light, PHDF exhibited wonderful photo-thermal conversion performance which not only brings excellent photo-thermal therapy (PTT) effect, but also promotes the uptake of Dox and the production of·OH, leading to enhanced CT and CDT efficacy. Taken together, the PHDF nanoplatform constructed in this study shows good CT/PTT/CDT combined therapy against tumor cells and it also provides a promising alternative for the combination therapy of tumors.