Tumor-Targeted Injectable Double-Network Hydrogel for Prevention of Breast Cancer Recurrence and Wound Infection via Synergistic Photothermal and Brachytherapy

Abstract

The high locoregional recurrence rate and potential wound infection in breast cancer after surgery pose enormous risks to patient survival. In this study, a polyethylene glycol acrylate (PEGDA)-alginate double-network nanocomposite hydrogel (GPA) embedded with 125I-labeled RGDY peptide-modified gold nanorods (125I-GNR-RGDY) is fabricated. The double-network hydrogel is formed by injection of GPA precursor solutions into the cavity of resected cancerous breasts of mice where gelation occurred rapidly. The enhanced temperature-induced PEGDA polymerization driven by near-infrared light irradiation, and then, the second polymer network is crosslinked between alginate and endogenous Ca2+ around the tumor. The double-network hydrogel possesses a dense polymer network and tightly fixes 125I-GNR-RGDY, which exhibit superior persistent photothermal and radioactive effects. Hyperthermia induced by photothermal therapy can inhibit self-repair of damaged DNA and promote blood circulation to improve the hypoxic microenvironment, which can synergistically enhance the therapeutic efficacy of brachytherapy and simultaneously eliminate pathogenic bacteria. Notably, this nanocomposite hydrogel facilitates antibacterial activity to prevent potential wound infection and is tracked by single-photon emission computerized tomography imaging owing to isotope labeling of loaded 125I-GNR-RGDY. The combination of photothermal therapy and brachytherapy has enabled the possibility of proposing a novel postoperative adjuvant strategy for preventing tumor recurrence and wound infection.