Pt(IV) prodrug initiated microparticles from microfluidics for tumor chemo-, photothermal and photodynamic combination therapy

Multimodal treatment modalities hold great potential for cancer therapy, thus current efforts are focusing on the development of more effective and practical synergistic therapeutic platforms. Herein, we present a novel trans, trans,trans-Pt(N3)2(OH)2(py)2 (Pt(IV)) prodrug-initiated hydrogel microparticles (MICG-Pt) with indocyanine green (ICG) encapsulation by microfluidics for efficiently synergistic chemo-, photothermal (PTT) and photodynamic therapy (PDT). The employed Pt(IV) could not only serves as an initiator to generate azidyl radical (N3•) for photo-polymerization of methacrylate gelatin (GelMA) matrix, but also be reduced to high cytotoxic platinum(II) (Pt(II)) species for tumor chemotherapy. The laden ICG with highly photothermal heating ability and intrinsic reactive oxygen species (ROS) productivity endows the MICG-Pt with effective PTT/PDT performances upon near-infrared (NIR) light irradiation. In addition, benefiting from the production of oxygen during the photo-activation process of Pt(IV), the PDT efficacy of ICG-laden MICG-Pt could be further enhanced. Based on these advantages, we have demonstrated that the MICG-Pt could significantly eliminate cancer cells in vitro, and remarkably suppressed the tumor growth in vivo via synergistic chemotherapy, PTT, and PDT. These results indicate that such Pt(IV)-initiated hydrogel microparticles are ideal candidates of multimodal treatment platforms, holding great prospects for cancer therapy.