Responsive accumulation of ultrasmall DNA@WO3-x nanodots for suppressing tumor progression and metastasis via single-nanodot triple-therapeutic effects.

Abstract

Effective treatment for malignant tumors continues to represent an urgent unmet clinical need. Triple-negative breast cancer (TNBC) constitutes a therapeutic challenge on account of its aggressive nature and limited response to conventional therapies. Radiotherapy serves as a cornerstone for cervical cancer treatment. Nevertheless, radioresistance frequently gives rise to therapeutic failure in cervical cancer. We developed ultrasmall, pH-responsive DNA@WO3-x nanodots to enhance the accumulation of nanodots within tumors, thereby improving therapeutic efficacy. The nanodots undergo intelligent self-assembly within the acidic tumor microenvironment, leading to enhanced accumulation and retention. DNA@WO3-x functions dually as an effective computed tomography (CT) contrast agent for tumor visualization and a potent radiosensitizer. The high-Z element tungsten and remarkable photothermal conversion capability in the NIR-II window enable synergistic radio-photothermal therapy (RT-PTT). In vitro and in vivo studies demonstrated that the combined treatment via single-nanodot triple-therapeutic effects potently suppresses the growth of tumor cells. Consequently, this synergistic strategy achieved remarkable inhibition of primary tumor growth and suppression of distant metastasis in orthotopic TNBC models, with no significant systemic toxicity observed. Furthermore, in vitro validation experiments verified that the developed nanodots can effectively sensitize cervical cancer cells to radiotherapy, thereby achieving prominent anti-tumor therapeutic effects. This work presents a versatile and integrated theranostic strategy that realizes potent tumor suppression via single-nanodot triple-therapeutic effects, offering a promising approach for the precise and effective treatment of aggressive solid tumors.