An injectable nanocomposite hydrogel with deep penetration ability for enhanced photothermal and chemotherapy

The excessive extracellular matrix (ECM) in solid tumors significantly inhibits the deep penetration and homogeneous distribution of nanodrugs, which greatly reduces the therapeutic efficacy. In the present work, an injectable polyelectrolyte hydrogel (CD@IPH) containing collagenase and doxorubicin-loaded polyacrylic acid@polyaniline nanoparticles (DOX@NP) were developed for improved photothermal and chemotherapy. The collagenase is released quickly from the polyelectrolyte hydrogel in the first 12 h, effectively degrading ECM and enhancing the deep penetration and evenly distribution of DOX@NP in tumor tissues. Then, the tumor microenvironment-triggered release of DOX from DOX@NP exhibits improved photothermal and chemotherapeutic efficiency. Owing to the excellent photoacoustic and photothermal properties of polyaniline inner cores of DOX@NP, the drug penetration process can be monitored to enable the image-guided cancer therapy. Both in vitro and in vivo assays prove the superior therapeutic efficacy of collagenase-enhanced photothermal and chemotherapy. The designed nanocomposite hydrogel therefore provides a versatile drug delivery system for deep tumor synergistic therapies.