Activity of Psoralen-Functionalized Nanoscintillators against Cancer Cells upon X-ray Excitation

Abstract

We report development of a nanoparticle-based, X-ray-activated anticancer "nanodrug" composed of yttrium oxide (Y(2)O(3)) nanoscintillators, a fragment of the HIV-1 TAT peptide, and psoralen. In this formulation, X-ray radiation is absorbed by the Y(2)O(3) nanoscintillators, which then emit UVA light. Absorption of UVA photons by nanoparticle-tethered psoralen has the potential to cross-link adenine and thymine residues in DNA. UVA-induced cross-linking by free psoralen upon activation with UVA light has previously been shown to cause apoptosis in vitro and an immunogenic response in vivo. Studies using the PC-3 human prostate cancer cell line demonstrate that X-ray excitation of these psoralen-functionalized Y(2)O(3) nanoscintillators yields concentration-dependent reductions in cell number when compared to control cultures containing psoralen-free Y(2)O(3) nanoscintillators.

Exchange of a Tetrapositive Cation into a Zeolite and a New Inorganic Scintillator. I. Crystal Structures and Scintillation Properties of Anhydrous Zr1.7Tl5.4Cl1.7–LTA and Zr2.1Tl1.6Cl3.0–LTA

“…The crystal was then heated under vacuum at 553 K for additional 24 h to distill away any excess ZrCl 4 and TlCl that might be near the crystal or loosely held within. After being allowed to cool to room temperature, the capillary containing the crystal was sealed off under vacuum from the reaction vessel.…”

“…1-3 Nanoparticle based scintillating materials have attracted special attention due to their wide range of applications including some in medicine. For example, Scaffidi et al demonstratedthat psoralen-functionalized nanoscintillators were capable of killing or inhibiting the growth of cells upon X-ray excitation 4. …”

Furanocoumarins

“…One of the most effective scintillating nanoparticle configurations is the combination of a psoralen such as 8-MOP and a fragment of the HIV-1 TAT cell-penetrating/nucleartargeting peptide anchored to UVA radiation-emitting Y 2 O 3 (yttrium oxide) nanoscintillators. Using this combination, Scaffidi et al showed the first evidence of drug-associated, X-ray-activated reduction in the PC-3 human prostate cancer cell growth for psoralen tethered to scintillating nanomaterials [246]. Further analyses of this and other formulations as well as their in vivo animal models efficacy will be evaluated in the future.…”

Engineering Nanomaterials for Biosensors and Therapeutics

“…If nanoscintillator materials can be prepared with low toxicity and easily modified with biomarkers and photosensitizers, these materials might be promising for use in X-ray-induced PDT. Indeed, a photosensitive nanocomposite comprising 12 nm Y 2 O 3 nanoscintillator bioconjugated with psoralen can be excited by X-ray and emits 370 nm UV light to kill tumor cells in vitro more effectively than using Y 2 O 3 alone [121].…”