Dual-modality, fluorescent, PLGA encapsulated bismuth nanoparticles for molecular and cellular fluorescence imaging and computed tomography

Abstract

Reports of molecular and cellular imaging using computed tomography (CT) are rapidly increasing. Many of these reports use gold nanoparticles. Bismuth has similar CT contrast properties to gold while being approximately 1000-fold less expensive. Herein we report the design, fabrication, characterization, and CT and fluorescence imaging properties of a novel, dual modality, fluorescent, polymer encapsulated bismuth nanoparticle construct for computed tomography and fluorescence imaging. We also report on cellular internalization and preliminary in vitro and in vivo toxicity effects of these constructs. 40 nm bismuth(0) nanocrystals were synthesized and encapsulated within 120 nm Poly(DL-lactic-co-glycolic acid) (PLGA) nanoparticles by oil-in-water emulsion methodologies. Coumarin-6 was co-encapsulated to impart fluorescence. High encapsulation efficiency was achieved ∼ 70% bismuth w/w. Particles were shown to internalize within cells following incubation in culture. Bismuth nanocrystals and PLGA encapsulated bismuth nanoparticles exhibited >90% and >70% degradation, respectively, within 24 hours in acidic, lysosomal environment mimicking media and both remained nearly 100% stable in cytosolic/extracellular fluid mimicking media. μCT and clinical CT imaging was performed at multiple X-ray tube voltages to measure concentration dependent attenuation rates as well as to establish the ability to detect the nanoparticles in an ex vivo biological sample. Dual fluorescence and CT imaging is demonstrated as well. In vivo toxicity studies in rats revealed neither clinically apparent side effects nor major alterations in serum chemistry and hematology parameters. Calculations on minimal detection requirements for in vivo targeted imaging using these nanoparticles are presented. Indeed, our results indicate that these nanoparticles may serve as a platform for sensitive and specific targeted molecular CT and fluorescence imaging.

In Vivo Microcomputed Tomography of Nanocrystal-Doped Tissue Engineered Scaffolds

“…Nanocrystal samples were zinc oxide (ZnO) (10–30 nm, SkySpring Nanomaterials, Inc.), gadolinium oxide (Gd 2 O 3 ) (<100 nm, SkySpring Nanomaterials, Inc.), zirconium oxide (ZrO 2 ) (<100 nm, Sigma-Aldrich), or bismuth (Bi) nanocrystals (~40 nm, synthesized by reduction of bismuth dodecanethiolate by tri- n -octylphosphine). 24 For each nanocrystal, an agarose and an alginate sample were made containing a concentration of 15, 30, 50, 75, and 100 mM of the nanocrystals (concentration of the high Z-metal). The agarose samples were bath sonicated for 20 min to disperse the nanocrystals throughout then heated in a boiling water bath and immediately placed in an ice bath to gel.…”

Heterocyclic Bismuth(III) Dithiocarbamato Complexes as Single‐Source Precursors for the Synthesis of Anisotropic Bi2S3 Nanoparticles

“…[1][2][3][4][5] Among these materials, bismuth sulfide (Bi 2 S 3 ), owing to its high figure of merit (ZT value)w ith al arge absorption coefficient and high energy conversion efficiency,i sw idely used as at hermoelectric-cooling material. [1][2][3][4][5] Among these materials, bismuth sulfide (Bi 2 S 3 ), owing to its high figure of merit (ZT value)w ith al arge absorption coefficient and high energy conversion efficiency,i sw idely used as at hermoelectric-cooling material.…”

“…Semiconductor materialso ft ype V-VI have recently attracted attention due to their photoconductive, photosensitive, thermoelectric and fluorescencep roperties. [1][2][3][4][5] Among these materials, bismuth sulfide (Bi 2 S 3 ), owing to its high figure of merit (ZT value)w ith al arge absorption coefficient and high energy conversion efficiency,i sw idely used as at hermoelectric-cooling material. It has ad irect energy bandgapb etween 1.3 and 1.7 eV and finds applications in photovoltaic converters [6] and photodiode arrays.…”

Three-dimensional visualisation of soft biological structures by X-ray computed micro-tomography

“…A current research goal is to determine effective particle compositions for microCT contrast agents to label and visualise live cells; so far, gold and bismuth nanoparticles have been used successfully (Naha et al, 2014;Swy et al, 2014;Zhu et al, 2014). These studies demonstrate that 40-nm bismuth particle cores encapsulated in 120-nm poly(lactic-coglycolic acid) (PLGA) are biocompatible and able to offer economical advantage over gold, which is 1000 times more expensive than bismuth.…”