title: Noninvasive fluorescence resonance energy transfer imaging of in vivo premature drug release from polymeric nanoparticles.
abstract: Understanding in vivo drug release kinetics is critical for the development of nanoparticle-based delivery systems. In this study, we developed a fluorescence resonance energy transfer (FRET) imaging approach to noninvasively monitor in vitro and in vivo cargo release from polymeric nanoparticles. The FRET donor dye (DiO or DiD) and acceptor dye (DiI or DiR) were individually encapsulated into poly(ethylene oxide)-b-polystyrene (PEO-PS) nanoparticles. When DiO (donor) nanoparticles and DiI (acceptor) nanoparticles were coincubated with cancer cells for 2 h, increased FRET signals were observed from cell membranes, suggesting rapid release of DiO and DiI to cell membranes. Similarly, increased FRET ratios were detected in nude mice after intravenous coadministration of DiD (donor) nanoparticles and DiR (acceptor) nanoparticles. In contrast, another group of nude mice i.v. administrated with DiD/DiR coloaded nanoparticles showed decreased FRET ratios. Based on the difference in FRET ratios between the two groups, in vivo DiD/DiR release half-life from PEO-PS nanoparticles was determined to be 9.2 min. In addition, it was observed that the presence of cell membranes facilitated burst release of lipophilic cargos while incorporation of oleic acid-coated iron oxide into PEO-PS nanoparticles slowed the release of DiD/DiR to cell membranes. The developed in vitro and in vivo FRET imaging techniques can be used to screening stable nanoformulations for lipophilic drug delivery.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan , Ann Arbor, Michigan 48109, United States.
authors.forename: Peng
authors.initials: P
authors.lastname: Zou
authors.forename: Hongwei
authors.initials: H
authors.lastname: Chen
authors.forename: Hayley J
authors.initials: HJ
authors.lastname: Paholak
authors.forename: Duxin
authors.initials: D
authors.lastname: Sun
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D031541:Fluorescence Resonance Energy Transfer / Q000379:methods*; D006801:Humans; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D011137:Polystyrenes / Q000737:chemistry
chemical_list: D011108:Polymers; D011137:Polystyrenes; C541965:polystyrene-b-poly(ethylene oxide); D011092:Polyethylene Glycols
references.citation: Langmuir. 2008 May 20;24(10):5213-7
references.pmid: 18257595
references.citation: Clin Cancer Res. 2002 Sep;8(9):2992-9
references.pmid: 12231546
references.citation: Mol Pharm. 2012 Feb 6;9(2):248-60
references.pmid: 22204437
references.citation: Biochim Biophys Acta. 2000 Jul 31;1467(1):101-12
references.pmid: 10930513
references.citation: Pharm Res. 1993 Jul;10(7):1093-5
references.pmid: 8378254
references.citation: Mol Pharm. 2010 Dec 6;7(6):1974-84
references.pmid: 20845930
references.citation: J Med Chem. 2008 Jun 12;51(11):3288-96
references.pmid: 18465845
references.citation: J Gen Physiol. 1979 Nov;74(5):643-6
references.pmid: 512634
references.citation: Pharm Res. 2012 Feb;29(2):448-59
references.pmid: 21879388
references.citation: Drug Metab Dispos. 2008 Aug;36(8):1709-15
references.pmid: 18490436
references.citation: Phys Rev E Stat Nonlin Soft Matter Phys. 2008 Mar;77(3 Pt 1):031806
references.pmid: 18517413
references.citation: Br J Cancer. 2004 Jun 1;90(11):2085-91
references.pmid: 15150584
references.citation: J Control Release. 2006 Nov 28;116(2):139-49
references.pmid: 16926059
references.citation: Macromolecules. 2011 Aug 9;44(15):6002-6008
references.pmid: 21818161
references.citation: Expert Opin Drug Metab Toxicol. 2010 Dec;6(12):1477-91
references.pmid: 20969450
references.citation: Nat Nanotechnol. 2007 Dec;2(12):751-60
references.pmid: 18654426
references.citation: Biochemistry. 1985 Jan 29;24(3):582-6
references.pmid: 3994976
references.citation: J Mol Biol. 1983 May 15;166(2):211-7
references.pmid: 6854644
references.citation: Mol Biol Cell. 2004 Aug;15(8):3509-19
references.pmid: 15169870
references.citation: J Chromatogr B Analyt Technol Biomed Life Sci. 2010 Feb 1;878(3-4):315-26
references.pmid: 20022309
references.citation: Angew Chem Int Ed Engl. 2012 Mar 19;51(12):2864-9
references.pmid: 22253091
references.citation: Noise Health. 2002;4(14):15-24
references.pmid: 12678924
references.citation: Biophys J. 2002 Dec;83(6):3652-64
references.pmid: 12496132
references.citation: J Am Chem Soc. 2010 Aug 11;132(31):10683-5
references.pmid: 20681699
references.citation: Mol Pharm. 2009 Jan-Feb;6(1):190-201
references.pmid: 19035785
references.citation: Pharm Res. 2006 Mar;23(3):460-74
references.pmid: 16400516
references.citation: Biophys J. 1998 May;74(5):2702-13
references.pmid: 9591694
references.citation: Biophys J. 2001 Oct;81(4):2395-402
references.pmid: 11566809
references.citation: Proc Natl Acad Sci U S A. 2008 May 6;105(18):6596-601
references.pmid: 18445654
references.citation: Anal Biochem. 1995 Dec 10;232(2):149-57
references.pmid: 8747469
references.citation: Pharm Res. 2012 Jan;29(1):69-82
references.pmid: 21739321
references.citation: Biomaterials. 2011 Aug;32(22):5148-57
references.pmid: 21546083
references.citation: Mol Pharm. 2010 Aug 2;7(4):1355-60
references.pmid: 20575526
references.citation: Biotechnol Bioeng. 2010 Nov 1;107(4):633-41
references.pmid: 20552670
references.citation: Neuro Oncol. 2007 Oct;9(4):393-403
references.pmid: 17652269
references.citation: Angew Chem Int Ed Engl. 2010 Nov 2;49(45):8426-30
references.pmid: 20718010
references.citation: J Control Release. 2008 Oct 6;131(1):2-4
references.pmid: 18625275
references.citation: J Cell Sci. 2012 Feb 1;125(Pt 3):743-50
references.pmid: 22389408