Drug-Loaded Mesoporous Tantalum Oxide Nanoparticles for Enhanced Synergetic Chemoradiotherapy with Reduced Systemic Toxicity

Abstract

Combining chemotherapy and radiotherapy (chemoradiotherapy) has been widely applied in many clinical practices, showing promises in enhancing therapeutic outcomes. Nontoxic nanocarriers that not only are able to deliver chemotherapeutics into tumors, but could also act as radiosensitizers to enhance radiotherapy would thus be of great interest in the development of chemoradiotherapies. To achieve this aim, herein mesoporous tantalum oxide (mTa₂ O₅ ) nanoparticles with polyethylene glycol (PEG) modification are fabricated. Those mTa₂ O₅ -PEG nanoparticles could serve as a drug delivery vehicle to allow efficient loading of chemotherapeutics such as doxorubicin (DOX), whose release appears to be pH responsive. Meanwhile, owing to the interaction of Ta with X-ray, mTa₂ O₅ -PEG nanoparticles could offer an intrinsic radiosensitization effect to increase X-ray-induced DNA damages during radiotherapy. As a result, DOX-loaded mTa₂ O₅ -PEG (mTa₂ O₅ -PEG/DOX) nanoparticles can offer a strong synergistic therapeutic effect during the combined chemoradiotherapy. Furthermore, in chemoradiotherapy, such mTa₂ O₅ -PEG/DOX shows remarkably reduced side effects compared to free DOX, which at the same dose appears to be lethal to animals. This work thus presents a new type of mesoporous nanocarrier particularly useful for the delivery of safe and effective chemoradiotherapy.

Keywords: chemoradiotherapy; drug delivery; mesoporous tantalum oxide; systemic toxicity.