PMID- 25248645 OWN - NLM STAT- MEDLINE DCOM- 20160515 LR - 20211021 IS - 2040-3372 (Electronic) IS - 2040-3364 (Print) IS - 2040-3364 (Linking) VI - 6 IP - 21 DP - 2014 Nov 7 TI - Dual-modality, fluorescent, PLGA encapsulated bismuth nanoparticles for molecular and cellular fluorescence imaging and computed tomography. PG - 13104-12 LID - 10.1039/c4nr01405g [doi] AB - 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 approximately 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. muCT 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. FAU - Swy, Eric R AU - Swy ER AD - Department of Radiology, Michigan State University, East Lansing, MI 48824, USA. erik.shapiro@rad.msu.edu. FAU - Schwartz-Duval, Aaron S AU - Schwartz-Duval AS FAU - Shuboni, Dorela D AU - Shuboni DD FAU - Latourette, Matthew T AU - Latourette MT FAU - Mallet, Christiane L AU - Mallet CL FAU - Parys, Maciej AU - Parys M FAU - Cormode, David P AU - Cormode DP FAU - Shapiro, Erik M AU - Shapiro EM LA - eng GR - DP2 OD004362/OD/NIH HHS/United States GR - R00 EB012165/EB/NIBIB NIH HHS/United States GR - DP2 OD001886/OD/NIH HHS/United States GR - R21 EB017881/EB/NIBIB NIH HHS/United States GR - DP2 OD001880/OD/NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - England TA - Nanoscale JT - Nanoscale JID - 101525249 RN - 0 (Contrast Media) RN - 0 (Coumarins) RN - 0 (Thiazoles) RN - 0 (coumarin 6) RN - 1SIA8062RS (Polylactic Acid-Polyglycolic Acid Copolymer) RN - 26009-03-0 (Polyglycolic Acid) RN - 33X04XA5AT (Lactic Acid) RN - U015TT5I8H (Bismuth) SB - IM MH - Animals MH - Apoptosis MH - Bismuth/*chemistry MH - Cell Proliferation MH - Cell Survival MH - Chickens MH - Contrast Media/chemistry MH - Coumarins/chemistry MH - Lactic Acid/*chemistry MH - Lysosomes/metabolism MH - Male MH - Metal Nanoparticles/*chemistry MH - Mice MH - Microscopy, Electron, Transmission MH - *Microscopy, Fluorescence MH - Nanoparticles/chemistry MH - Nanotechnology MH - Polyglycolic Acid/*chemistry MH - Polylactic Acid-Polyglycolic Acid Copolymer MH - Rats MH - Rats, Sprague-Dawley MH - *Spectrometry, Fluorescence MH - Temperature MH - Thiazoles/chemistry MH - *Tomography, X-Ray Computed MH - X-Ray Microtomography PMC - PMC4362618 MID - NIHMS630841 EDAT- 2014/09/25 06:00 MHDA- 2016/05/18 06:00 PMCR- 2015/11/07 CRDT- 2014/09/25 06:00 PHST- 2014/09/25 06:00 [entrez] PHST- 2014/09/25 06:00 [pubmed] PHST- 2016/05/18 06:00 [medline] PHST- 2015/11/07 00:00 [pmc-release] AID - 10.1039/c4nr01405g [doi] PST - ppublish SO - Nanoscale. 2014 Nov 7;6(21):13104-12. doi: 10.1039/c4nr01405g.