Constructing pH-sensitive silica-sulfide hafnium dot nanotherapeutics for synergistically enhanced chemoradiotherapy

Inorganic nanoparticles play important roles in cancer treatment, but the issues of biodegradable properties, and tumor penetration restricted further clinical application. Aiming at the low efficiency and toxic side effects problems existing in the current clinical treatment of cancer, a biodegradable mesoporous silica nanoparticle (MSN) platform integrating pH-responsive drug release and synergistic chemo-radiotherapy was developed. The doxorubicin hydrochloride (DOX) was loaded in MSNs via electrostatic interactions, with ultra-small hafnium sulfide (HfS 2 ) nanodots were anchored to the surface of MSN. At physiological pH, HfS₂ reinforces DOX retention through steric and electrostatic effects, while in acidic tumor microenvironments, it triggers DOX release. Concurrently, dissociated HfS 2 acts as a radiosensitizer, enhancing X-ray-induced cytotoxicity and promoting deep tumor penetration. Both the in vitro cellular and in vivo animal level results confirmed synergistically enhanced chemoradiotherapy efficiency. Therefore, this research, we believed, will bring a new train of thought and scientific support for more safety and more efficiency in cancer therapy.