Nonspecificity and high toxicity limit the treatment efficacy and safety of chemoradiation therapy. Effective tumor targeting of anticancer drugs and radiosensitizing agents is highly desirable to amplify the efficacy of this standard cancer therapy approach. To achieve this goal, we exploited the synergy of cisplatin and gold nanoparticles (AuNPs) co-loaded into alginate hydrogel network, forming so-called ACA nanocomplex, and X-ray radiation. Cisplatin is a commonly used anticancer agent, and at the same time, along with AuNPs could function as radiosensitizers to enhance the radiation-induced damages through various pathways. The ACA nanocomplex improved the therapeutic efficiency of standard chemotherapy and yielded 79% growth inhibition in CT26 colon adenocarcinoma tumor after 28 days, which was significantly higher than that of 9% for free cisplatin administration. Moreover, the combination of ACA nanocomplex with 6 MV X-ray dramatically suppressed tumor growth up to 95%, showing 51% enhancement in antitumor activity compared to standard chemoradiation. The nanocomplex developed herein holds the promise to promote the efficiency of standard chemoradiation while maintaining the patient's safety through reducing the clinically administered doses of anticancer drug and X-ray. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B:2658-2663, 2019.

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