Journal
RSC ADVANCES
Volume 10, Issue 40, Pages 23759-23766Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/d0ra01878c
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Funding
- National Institutes of Health (NIH) [U54 CA199092, R01 EB021048]
- NIH [R01 CA171651, P50 CA094056, P30 CA091842, S10 OD020129, S10 OD016237, S10 RR031625]
- Department of Defense Breast Cancer Research Program [W81XWH-16-1-0286]
- Alvin J. Siteman Cancer Center Investment Program Research Development Award
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Radionuclide-stimulated therapy (RaST), which is enhanced by Cherenkov radiation, has enabled deep tissue stimulation of UV photosensitizers, providing a new path for cancer treatment. Previous reports have shown UV-active titanium dioxide (TiO2) nanoparticles (NPs) modified with transferrin inhibit tumour growth after orthogonal treatment with Cherenkov radiation-emitting radionuclides such as(18)F-fluorodeoxyglucose (FDG). However, poor understanding of TiO2NP parameters on reactive oxygen species (ROS) generation and particle distribution limits effective therapy. Here we sought to delineate the effects of crystal phase and core TiO(2)crystal dimension (cTd) on ROS production and particle morphology. We prepared Transferrin (Tf)-TiO(2)nanoaggregates (NAGs) using solvothermally synthesized cTd sizes from 5 to 1000 nm diameter and holo- or apo-transferrin. Holo-transferrin was unable to stabilize TiO(2)NPs while apo-transferrin stabilized TiO(2)into uniform nanoaggregates (NAGs), which were invariant with differing cTd, averaging 116 +/- 1.04 nm for cTds below 100 nm. ROS production increased from 5 to 25 nm cTd, attaining a peak at 25 nm before decreasing with larger sizes. The supra-25 nm ROS production decrease was partially driven by a similar to 1/r(3)surface area decline. Additionally, amorphous TiO(2)of equal core size exhibited a 2.6-fold increase in ROS production compared to anatase NAGs, although limited stability halted further use. Although both 5 and 25 nm anatase cTds formed similarly sized NAGs, 5 nm anatase showed a four-fold higher tumour-to-muscle ratio than the 25 nm NPs in tumour-bearing mice, demonstrating the intricate relationships between physical and biological properties of NAGs. The combinedin vivoand ROS results demonstrate that anatase crystals and cTd size of 25 nm or less are ideal particle parameters to balance biodistribution with ROS production efficiency.
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