cRGD-Targeted MXene Nanocomposite Delivers Potent Bladder Cancer Therapy via Dual PTT/PDT and Immune Activation

Treating bladder cancer remains challenging, with conventional therapies often facing issues like drug resistance, systemic toxicity, and limited efficacy. Photothermal therapy (PTT) and photodynamic therapy (PDT) offer non-invasive alternatives, but current photothermal agents frequently suffer from poor tumor accumulation, non-specific thermal damage, and insufficient monotherapy effects. There's a critical need for targeted, multi-modal platforms that can enhance therapeutic outcomes while minimizing off-target effects. This study addresses this gap by developing a novel nanocomposite designed for precise tumor targeting and synergistic PTT/PDT, aiming to improve treatment specificity and potency.

Researchers engineered a multifunctional MXene-based nanocomposite by integrating MnFe2O4 nanoparticles onto TiVNbMoC3 MXene nanosheets, forming a layer-on-layer Schottky junction. This core was then conjugated with cRGD peptides for specific tumor targeting. The team confirmed successful synthesis, colloidal stability, broad optical absorption, and efficient photothermal conversion and ROS generation under 808 nm laser irradiation. In vitro assessments utilized 5637 bladder cancer cells to evaluate proliferation, migration, colony formation, apoptosis, and immunogenic cell death. In vivo efficacy was tested in a murine bladder tumor model, comparing the nanocomposite's performance against doxorubicin (DOX), with biocompatibility also assessed.

The engineered MnFe2O4/TiVNbMoC3-cRGD nanocomposite demonstrated robust characteristics, including favorable colloidal stability and efficient ROS generation under 808 nm laser irradiation. In vitro, the cRGD-targeted nanocomposite was efficiently internalized by 5637 bladder cancer cells, exhibiting significantly higher anticancer efficacy than doxorubicin (DOX). This included potent inhibition of proliferation, migration, and colony formation, alongside strong induction of apoptosis and immunogenic cell death. In the murine bladder tumor model, the nanocomposite achieved the strongest tumor growth suppression. > The nanocomposite reduced final tumor volume more effectively than DOX, showcasing superior therapeutic outcomes. Biocompatibility studies confirmed minimal hemolysis and no major organ damage at therapeutic doses, suggesting a favorable safety profile for the novel platform.