Hollow gold nanoshells-incorporated injectable genetically engineered hydrogel for sustained chemo-photothermal therapy of tumor

BACKGROUND: Combined therapy has demonstrated to be an effective strategy for cancer therapy. Herein, an injectable hydrogel based on the genetically engineered polypeptide and hollow gold nanoshells (HAuNS) has been developed for chemo-photothermal therapy of HepG2 tumor. METHODS: PC(10)A/DOX/HAuNS nanogel was prepared with layer-by-layer through the adsorption of DOX and PC(10)A successively. DOX with positive charge and PC(10)A with negative charge were coated step by step onto the surface of negatively charged HAuNS. The multifunctional hydrogel PC(10)A/DOX/HAuNS were prepared via dissolving hybrid PC(10)A/DOX/HAuNS nanogel in polypeptide PC(10)A. Chemotherapy drug DOX in the PC(10)A/DOX/HAuNS hydrogel was absorbed on the HAuNS and directly embedded in the PC(10)A hydrogel, which contributes to sequentially release of the drug. Specifically, DOX adsorbed on the HAuNS could be released slowly for sustainable chemotherapy. RESULTS: The PC(10)A/DOX/HAuNS hydrogel could pass 26-gauge needle without clogging, indicating that it is injectable. In addition, the PC(10)A/DOX/HAuNS hydrogel possessed outstanding photothermal effect and photothermal stability. In both in vitro cell and in vivo tumor-bearing mice experiments, a remarkably enhance tumor inhibition was observed by the combined therapy of chemo-photothermal therapy compared with photothermal therapy or chemotherapy alone. CONCLUSIONS: The combined chemotherapy and photothermal therapy of PC(10)A/DOX/HAuNS hydrogels could significantly improve the therapeutic effect. Therefore, the multifunctional hydrogel PC(10)A/DOX/HAuNS is promising to provide a new strategy for sustained chemo-photothermal therapy.