Advancements in nanoparticle (NP) design can transform Computed Tomography (CT) into a robust molecular imaging platform. Various NPs based on Au, Bi, Ta, etc. have been investigated to substitute for iodine-based Contrast Agents (CAs) currently approved for clinical use. The drawback of CT is the low sensitivity of CT contrast agents; currently 10’s mM is required for detection. As such, pre-amplified radiopaque contrast agents are necessary to realize the molecular imaging potential of CT. Nanocrystals (NCs) are such a pre-amplified system, with 1000’s of radiopaque atoms per NC. The purpose of this work was to develop flexible and biocompatible, pre-amplified NCs and nanoparticles (NPs) for CT. Two different NP platforms were fabricated using Tantalum Oxide (TaOx; k-edge 67.4 keV) NCs as the X-ray dense component. TaOx NCs with high Ta content (78%) were synthesized by a base-catalyzed sol-gel method. Encapsulation of bare NCs within mesoporous silica and PLGA was carried out to afford TaOx@MSNPs and TaOx@PLGA NPs, respectively. Both NP types were characterized for size, structure and composition using DLS, TEM, SEM, EDS and ICP-OES, and for biocompatibility in cell culture. The TaOx NCs and NPs were also evaluated in vivo. Following IV injection in BALB/c mice, TaOx NCs circulated in blood for ~3 hours, accumulating eventually in RES organs. Bolus IM injections of TaOx@PLGA NPs and TaOx@MSNPs produced significant contrast enhancement in BALB/c mice. We also report an intrinsic mesoporous structure for individual TaOx NCs, similar to the intricate pore structure in MSNPs. Both TaOx NCs and TaOx@MSNPs displayed higher Doxorubicin Hydrochloride (DOX) loading as compared to empty MSNPs, with a programmable pH dependent DOX release over 72 h. This work shows considerable promise for TaOx NCs/NPs in theranostics.

Investigating tantalum nanoparticles for X-ray CT and therapeutic use

2019 Fall National Meeting

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.