Highly efficient, targeted, and traceable perovskite nanocrystals for photoelectrocatalytic oncotherapy

Abstract

Metal halide perovskites have emerged as highly promising materials in optoelectronics, owing to their unique multidimensional crystal structures that impart exceptional optical and electronic properties. These materials exhibit remarkable fluorescence imaging and tracking capabilities, as well as efficient photoelectric conversion, making them suitable for a broad range of applications. Nevertheless, despite their significant potential, their poor water stability has posed a major challenge, particularly in biomedical fields such as drug delivery systems, biological imaging, and photoelectrocatalytic oncotherapy. This limitation has hindered their practical use in medical treatments and diagnostics. In this study, we address the water stability issue by successfully synthesizing CsSn_0.5Pb_0.5Br₃ perovskite nanocrystals (PeNCs) and conjugating them with methotrexate-chitosan-folic acid (MTX-CS-FA), resulting in innovative green light-emitting PeNCs@MTX-CS-FA nanoparticles. These nanoparticles exhibited remarkable water stability, maintaining their structural and functional integrity for up to 228 days, a significant improvement that enables their application in complex biological environments. Under visible light illumination, the nanoparticles demonstrated a dual-action therapeutic mechanism. The perovskites effectively generated electrons and reactive oxygen species (ROS), inducing oxidative stress in tumor cells. At the same time, photogenerated holes oxidized glutathione (GSH), a molecule that is typically overexpressed in tumor cells to protect against oxidative damage. By depleting GSH, the nanoparticles weakened the tumor cells' defense mechanisms, thereby enhancing the oxidative damage caused by ROS. In addition, methotrexate (MTX), a chemotherapeutic agent integrated into the system, inhibited dihydrofolate reductase (DHFR) activity. This inhibition disrupted tumor cell metabolism, particularly nucleotide synthesis, leading to lipid peroxidation and subsequent cell death. Together, these mechanisms generated a potent, synergistic therapeutic effect. The therapeutic efficacy of the PeNCs@MTX-CS-FA nanoparticles was validated through in vivo antitumor experiments in mice. A total dose of 2.4 ​mg of nanoparticles resulted in a 63.68 ​% reduction in tumor volume and a 63.26 ​% decrease in tumor weight, demonstrating significant tumor growth suppression. Biological safety evaluations further confirmed the nanoparticles' biocompatibility. Notably, they were excreted from the mice in their fluorescent form without decomposition, ensuring minimal long-term toxicity. This safe excretion pathway underscores the feasibility of repeated use of these nanoparticles in clinical applications. Overall, this study highlights the transformative potential of metal halide perovskites in cancer treatment. By overcoming the water stability limitations that have previously constrained their biomedical applications, the PeNCs@MTX-CS-FA nanoparticles exhibited outstanding capabilities in real-time bioimaging and effective photoelectrocatalytic chemotherapy, thus paving the way for future innovations in biomedical science.