Gram-scale synthesis of highly biocompatible and intravenous injectable hafnium oxide nanocrystal with enhanced radiotherapy efficacy for cancer theranostic

Abstract

Based on the ionizing radiation applied to the malignant tumor tissue, radiation therapy (RT) is the frequently-used non-surgical approach for cancer treatment. Hafnium Oxide (HfO₂) based nanoagent has been used in clinical trials for radiosensitized tumor therapy. However, the current reported clinically used HfO₂ nanoparticles are relay on intratumoral injectable, and the unmodified HfO₂ nanoparticles tend to be aggregated in serum and cannot be injected by intravenous route, which significantly limited the types of treatable cancer. To overcome the limitation, in this work, we developed a large-scalable, intravenously injectable, and clearable HfO₂ nanoassemblies (NAs) to enhance the radiotherapeutic effects. The HfO₂ NAs exhibited meaningfully promoted free-radical generation upon X-ray radiation for cancer cell killing due to the improved the sensitiveness of the breast cancer cells. The PEGylated HfO₂ NAs demonstrated efficient tumor-homing ability via intravenous injection and manifested by HfO₂ NAs enhanced CT imaging in a 4T1 breast tumor model. Utilizing the radiation sensitization function of HfO₂ NAs, excellent tumor killing efficacy was achieved via both intratumoral and intravenously injection administration. Importantly, our HfO₂ NAs could be degraded and excreted efficiently in a reasonable period in living body and avoid long-term toxicity. Taken together, our work provides a new technique by an injectable CT imaging-guided radio-sensitivitiable nanosystem for the further potential clinic translation.

Keywords: CT imaging; HfO(2) nanoassemblies; Intravenous injection; Large-scale and reproducible synthesis; Radiation therapy.