A biodegradable thermo-responsive hybrid hydrogel: Therapeutic applications in preventing the post-operative recurrence of breast cancer

Abstract

Smart hydrogels that undergo structural changes in response to stimuli (for example, pH, heat, light) have promising biomedical applications as delivery systems, especially for the locally controlled release of drugs. Early prevention of locoregional recurrence (LRR) is critical for patients who have undergone breast-conserving therapy. This work reports the preparation of a hybrid hydrogel system in which gold nanorods (GNRs) were doped into a thermally responsive hydrogel. A near-infrared (NIR) laser was used to trigger the release of loaded Doxorubicin (DOX) by utilizing the photothermal effect of GNRs to induce the contraction of the thermo-responsive hydrogels. In a 4T1 breast cancer model of the in vivo locoregional prevention of post-operative recurrence, we found that after NIR irradiation, DOX/GNR-embedded Methoxylpoly(ethylene glycol)-poly(ϵ-caprolactone)-acryloyl chloride (PECA)/glycidylmethacrylated chitooligosaccharide (COS-GMA)/N-isopropylacrylamide (NIPAm)/acrylamide (AAm) (PCNA) hydrogels (DOX-PCNA-GNR hydrogels) significantly reduced tumor recurrence to 16.7%, compared with 50% for DOX-PCNAGNRs without NIR irradiation, 83.3% for PCNA-GNRs with NIR irradiation, 100% for PCNA-GNRs without NIR irradiation, 83.3% for single systemic or local administration of Dox, 100% for intravenous DOX administration once or three times, and 100% for the blank control. This study demonstrates that these DOX-PCNA-GNR hybrid hydrogels with NIR-triggered thermo-responsive drug release exhibit great potential in preventing post-operation cancer relapse.