All-in-One Theranostic Nanoplatform Based on Hollow TaOx for Chelator-Free Labeling Imaging, Drug Delivery, and Synergistically Enhanced Radiotherapy

摘要

Despite extensive use of radiotherapy in cancer treatment, there has been huge demand to improve its efficacy and accuracy in tumor destruction. To this end, nanoparticle-based radiosensitizers, particularly those with high-Z elements, have been explored to enhance radiotherapy. Meanwhile, imaging is an essential tool prior to the individual planning of precise radiotherapy. Here, hollow tantalum oxide (H-TaOx) nanoshells are prepared using a onepot template-free method and then modified with polyethylene glycol (PEG), yielding H-TaOx-PEG nanoshells for imaging-guided synergistically enhanced radiotherapy. H-TaOx-PEG nanoshells show strong intrinsic binding with metal ions such as Fe3+ and Tc-99m(4+) upon simple mixing, enabling magnetic resonance imaging and single photon emission computed tomography imaging, respectively, which are able to track in vivo distribution of those nanoshells and locate the tumor. With mesoporous shells and large cavities, those H-TaOx-PEG nanoshells show efficient loading of 7-ethyl-10-hydroxycamptothecin (SN-38), a hydrophobic chemotherapeutic drug. By means of the radiosensitization effect of Ta to deposit X-ray energy inside tumors, as well as SN-38-induced cell cycle arrest into radiation-sensitive phases, H-TaOx-PEG@SN-38 can offer remarkable synergistic therapeutic outcome in the combined chemoradiotherapy. Without appreciable systemic toxicity, such hollow-TaOx nanostructure may therefore find promising applications in multimodal imaging and enhanced cancer radiotherapy.