Mesoporous polydopamine nanoplatforms loaded with calcium ascorbate for amplified oxidation and photothermal combination cancer therapy

Abstract

Abstract Background Destruction of cellular redox homeostasis to induce cancer cell apoptosis is an emerging tumor therapeutic strategy. To achieve this goal, elevating exogenous oxidative stress or impairing the antioxidant defense system of cancer cells is an effective method. Herein, we firstly report a biocompatible and versatile nanoplatform (MpDA/Vc-Ca/PCM) based on calcium ascorbate (Vc-Ca) loaded mesoporous polydopamine (MpDA) nanoparticles, which simultaneously realized ROS generation, suppression of tumor antioxidant capability, and hyperthermia co-enhanced oncotherapy. Methods In this design, Vc-Ca is first loaded into MpDA, and then phase change material (PCM) is wrapped onto the surface of MpDA to form MpDA/Vc-Ca/PCM. The temperature-controlled release of Vc-Ca is characterized. The photothermal performance and GSH consumption capacity of MpDA are evaluated. The cytotoxicity mechanism of Vc-Ca is systematacially investigated. To confirm the synergistic tumor therapeutic effects, in vitro and in vivo biological tests are implemented. Results Vc-Ca encapsulated in MpDA by PCM is controllably released due to the melting of PCM matrix in response to photothermal heating upon a near-infrared irradiation. Vc-Ca is proved to be a pro-oxidant that can promote production of ROS (H2O2) in tumor site. Remarkably, MpDA can not only act as a photothermal agent, but also can break the redox balance of cancer cells through depleting the primary antioxidant glutathione (GSH), thus amplifying Vc-Ca-mediated oxidative therapy. Both in vitro and in vivo results demonstrate the significantly enhanced antitumor activity of boosted ROS combined with local hyperthermia. Conclusion This study highlights the potential applications of Vc-Ca in cancer treatment, and the prepared multifunctional nanoplatform provides a novel paradigm for high-efficiency oxidation-photothermal therapy.