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

Abstract

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 based on mesoporous polydopamine (MpDA) nanoparticles and a phase-change material (PCM) for delivering calcium ascorbate (Vc-Ca), simultaneously enabling combination therapy of hyperthermia, reactive oxygen species (ROS) generation, and suppression of tumor antioxidant capability. In this design, Vc-Ca encapsulated in MpDA using PCM is controllably released due to the melting of PCM matrix in response to photothermal heating upon near-infrared irradiation. Vc-Ca is proved to be a pro-oxidant that can promote the production of ROS (H₂O₂) in the 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, 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. 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.