Injectable In-Situ Forming Hydrogels of Thermosensitive Polypyrrole Nanoplatforms for Precisely Synergistic Photothermal-Chemo Therapy.

The combination of PTT with chemotherapy has great potential to maximize synergistic effect of thermo-induced chemosensitization and improve treatment performance. For achieving high drug-loading capacity as well as precise synchronization between the controllable release of chemotherapeutics and the duration time span of NIR-PTT, in this work, a facile one-step method was firstly developed to fabricate a novel injectable in-situ forming photothermal modulated hydrogel drug delivery platform (D-PPy@PNAs), in which PNIPAM-based temperature-sensitive acidic triblock polymer (PNA) was utilized as the stabilizing agent in the polymerization of polypyrrole (PPy). The in-situ forming hydrogels showed sensitive temperature-sensitive sol-gel phase transition behavior as well as excellent photothermal property. The strong interaction of ionic bonds together with π-π stacking interactions resulted in high DOX-loading capacity and controlled/sustained drug release behavior. In addition, D-PPy@PNAs also displayed enhanced cellular uptake and promoted intratumoral penetration of DOX upon NIR laser irradiation. The synergistic photothermal-chemo therapy of D-PPy@PNA hydrogels greatly improved the anti-tumor efficacy in vivo. Therefore, thermosensitive polypyrrole-based D-PPy@PNA hydrogels may be a powerful drug delivery nanoplatforms for precisely synergistic photothermal-chemotherapy of tumors.