MRI/CT dual-model guided multifunctional acid neutralization nanoplatform for tumor alkalization combined photothermal-chemotherapy

The acidic tumor microenvironment (TME) frequently diminishes the overall uptake of chemotherapeutic drugs, leading to inefficient drug delivery and tumor resistance. To address this challenge, this study constructed a theranostic nanoplatform (PDA@ACC-DOX-Gd³⁺, abbreviated as PADG) via a simple alkaline vapor diffusion method. This system is designed to alkalize the acidic TME and allows for Magnetic resonance imaging /X-ray computed Tomography (MRI/CT) dual-modal imaging-guided photothermal therapy combined with alkalization-enhanced chemotherapy. The strategy employs in situ alkaline-induced polymerization to form a stable polydopamine (PDA) coating both within and on the surface of amorphous calcium carbonate (ACC), thereby overcoming the inherent instability, rapid dissolution, and recrystallization of ACC in aqueous environments. The resulting PADG not only neutralizes the TME through proton consumption, reducing the reversed pH gradient across tumor cell membranes and improving the utilization of weakly basic drugs, but also enhances tumor chemosensitivity through PDA-mediated photothermal therapy. Both in vitro and in vivo results confirm that PADG exhibits excellent dual-modal MRI/CT imaging performance, effectively consumes protons to alkalize the TME for improved drug efficacy, and achieves significant synergistic photothermal/chemotherapeutic antitumor outcomes.