Although multimodal
cancer therapy has shown superior antitumor efficacy in comparison to individual
therapy due to the potential generation of synergistic interactions among the treatments, its clinical usage is highly hampered by systemic dose-limiting toxicities. Herein, we developed a multi-responsive nanocomplex constructed from
alginate hydrogel co-loaded with
cisplatin and
gold nanoparticles (AuNPs) (abbreviated as ACA) to combine
chemotherapy,
radiotherapy (RT) and
photothermal therapy. The nanocomplex markedly improved the efficiency of drug delivery where ACA resulted in noticeably higher
tumor growth inhibition than free
cisplatin. The
tumor treated with ACA showed an increased heating rate upon 532 nm
laser irradiation, indicating the photothermal conversion ability of the nanocomplex. While RT alone resulted in slight
tumor growth inhibition, thermo-chemo
therapy, chemoradiation
therapy and thermo-radio
therapy using ACA dramatically slowed down the rate of
tumor growth. Upon 532 nm
laser and 6 MV X-ray, the nanocomplex could enable a trimodal thermo-chemo-radio
therapy that yielded complete
tumor regression with no evidence of relapse during the 90-days follow up period. The results of this study demonstrated that the incorporation of AuNPs and
cisplatin into
alginate hydrogel network can effectively combine
chemotherapy, RT and
photothermal therapy to achieve a locally synergistic
cancer therapy.