Doxorubicin-encapsulated thermosensitive liposome-functionalized photothermal composite scaffolds for synergistic photothermal therapy and chemotherapy

Abstract

Synergistic therapy, especially the combination of photothermal therapy and chemotherapy, has been proposed as an effective therapeutic approach for breast cancer treatment. In this study, a smart platform for synergistic photothermal therapy and chemotherapy was developed by hybridizing doxorubicin-encapsulated thermosensitive liposomes and gold nanorods into porous scaffolds of gelatin and polyglutamic acid (Dox-lipo/AuNR/Gel/PGA). The Dox-lipo/AuNR/Gel/PGA composite scaffolds had good photothermal conversion and temperature-dependent doxorubicin release properties. Under near-infrared laser irradiation, the composite scaffolds increased the local temperature to not only kill the breast cancer cells in the scaffolds but also accelerate the release of doxorubicin to eliminate the breast cancer cells surrounding the scaffolds. In vitro cell culture and in vivo mouse experiments demonstrated that the synergistic effects of photothermal ablation combined with doxorubicin-induced inhibition of the breast cancer cells in and surrounding the composite scaffolds under near-infrared laser irradiation. Moreover, after drug release was complete, the composite scaffolds fostered human bone marrow-derived mesenchymal stem cell proliferation. These results suggested that the composite scaffolds provided synergistic photothermal therapy and chemotherapy for breast cancer cell elimination at the early stage and promoted stem cell activities at the late stage. Therefore, this composite scaffold holds great potential as a synergistic therapy platform for breast cancer treatment.