An injectable thermosensitive photothermal-network hydrogel for near-infrared-triggered drug delivery and synergistic photothermal-chemotherapy

Near-infrared (NIR)-responsive hydrogels have exhibited remarkable advantages in biomedical applications especially for in situ therapeutic delivery, because of their deep-tissue penetration capacity, minimal invasiveness, and high spatiotemporal selectivity. Nevertheless, conventional NIR-responsive nanocomposite hydrogels suffer from the disadvantages of limited photothermal effect and potential leakage of the physically mixed photothermal nanoagents. To overcome these limitations, we herein designed an injectable thermosensitive photothermal-network hydrogel (PNT-gel) through the host-guest self-assembly of a photothermal conjugated polymers and ɑ-cyclodextrin. The conjugated-polymer backbones can directly convert incident light into heat, endowing the PNT-gel with high photothermal conversion efficiency (η = 52.6%) and enhanced photothermal stability. Meanwhile, the mild host-guest assembly enable the shear-thinning injectability, photothermally-driven and reversible gel-sol conversion of the hydrogel. Consequently, the remotely controlled on-demand release of doxorubicin (DOX) was achieved via photothermal-induced gel-sol transition. Because the backbone of the hydrogel absorbs NIR light and mediates the photothermal conversion itself, the PNT-gel demonstrated the advantage of a prolonged retention time and thus permitting repeatable NIR treatment after a one-time intratumoral injection of this hydrogel. Under repeated NIR laser irradiation (0.15 W cm-2), the synergistic photothermal-chemotherapy mediated by the PNT-gel almost completely eradicated 4T1 breast cancer. This work not only presents a multifunctional therapeutic platform integrated with inherent photothermal characteristic and reversible stimuli responsiveness for on-demand delivery and combinatorial photothermal-chemotherapy, but also provides a new strategy for the development of the next-generation of light-modulated intelligent hydrogels. STATEMENT OF SIGNIFICANCE: The conventional NIR-responsive nanocomposite hydrogels suffer from the disadvantages of limited photothermal effect and possible leakage of the physically mixed photothermal nano-components. To overcome these limitations, we hereby fabricated a NIR-responsive themosensitive photothermal-network hydrogel through the supramolecular assembly of conjugated polymer. The conjugated polymeric backbones of the hydrogel directly convert NIR light to heat, endowing the hydrogel with good photothermal effect and long-term photothermal stability. Meanwhile, the dynamic crosslinkages via supramolecular assembly enabled the shear-thinning injectability and reversible gel-sol transition of the hydrogel, facilitating the photothermal-induced drug release. Our strategy demonstrated the efficacy of using conjugated polymer as the backbone of hydrogel for the construction of a new injectable NIR-responsive hydrogel system with enhanced photothermal capabilities and improved therapy outcomes.