Synthesis of Hollow Biomineralized CaCO₃–Polydopamine Nanoparticles for Multimodal Imaging-Guided Cancer Photodynamic Therapy with Reduced Skin Photosensitivity

TLDR

Activatable nanoplatforms that enhance diagnosis and therapy while reducing side effects are highly sought after in precision cancer medicine. We develop a one‑pot, dopamine‑mediated biomineralization method to produce CaCO₃–PDA hollow nanoparticles as a multifunctional theranostic platform. The CaCO₃–PDA nanoparticles are pH‑responsive, rapidly degrading in slightly acidic tumor environments to restore Ce6 fluorescence and singlet oxygen production, while their PDA surface binds metal ions to provide multimodal imaging guidance for photodynamic therapy. At physiological pH the nanoparticles remain quenched, minimizing phototoxicity to normal tissues and reducing skin damage, yet they achieve high antitumor photodynamic efficacy in tumors.

Abstract

The development of activatable nanoplatforms to simultaneously improve diagnostic and therapeutic performances while reducing side effects is highly attractive for precision cancer medicine. Herein, we develop a one-pot, dopamine-mediated biomineralization method using a gas diffusion procedure to prepare calcium carbonate-polydopamine (CaCO3–PDA) composite hollow nanoparticles as a multifunctional theranostic nanoplatform. Because of the high sensitivity of such nanoparticles to pH, with rapid degradation under a slightly acidic environment, the photoactivity of the loaded photosensitizer, i.e., chlorin e6 (Ce6), which is quenched by PDA, is therefore increased within the tumor under reduced pH, showing recovered fluorescence and enhanced singlet oxygen generation. In addition, due to the strong affinity between metal ions and PDA, our nanoparticles can bind with various types of metal ions, conferring them with multimodal imaging capability. By utilizing pH-responsive multifunctional nanocarriers, effective in vivo antitumor photodynamic therapy (PDT) can be realized under the precise guidance of multimodal imaging. Interestingly, at normal physiological pH, our nanoparticles are quenched and show much lower phototoxicity to normal tissues, thus effectively reducing skin damage during PDT. Therefore, our work presents a unique type of biomineralized theranostic nanoparticles with inherent biocompatibility, multimodal imaging functionality, high antitumor PDT efficacy, and reduced skin phototoxicity.