Dual-Responsive Dextran-Based Nanosystem for NIR Dual-Modal Imaging-Guided Photothermal-Chemotherapy of Breast Cancer

Abstract Breast cancer is a highly prevalent malignancy, but the conventional single chemotherapy suffers from insufficient therapeutic outcomes. To overcome this challenge, this study developed a dextran-based prodrug nanogel (DDIR) with dual pH/GSH responsiveness to the tumor microenvironment, enabling near-infrared (NIR) fluorescence−photothermal dual-modal imaging-guided chemo-photothermal synergistic therapy. Specifically, DDIR was prepared by conjugating doxorubicin to aldehyde-functionalized dextran via acid-sensitive Schiff-base linkages, crosslinking with a disulfide-containing linker, and encapsulating the NIR-II photothermal agent IR-1061 through hydrophobic interactions. In the acidic tumor microenvironment with elevated glutathione (GSH) levels, DDIR release drugs of DOX and IR-1061, and efficiently suppresses tumor proliferation, and ablates tumor lesions in tumor-bearing mice. This study provides a novel theranostic platform for the synergistic treatment of breast cancer and holds a promising potential for clinical translation.