title: Real-time analysis of composite magnetic nanoparticle disassembly in vascular cells and biomimetic media.
abstract: The fate of nanoparticle (NP) formulations in the multifaceted biological environment is a key determinant of their biocompatibility and therapeutic performance. An understanding of the degradation patterns of different types of clinically used and experimental NP formulations is currently incomplete, posing an unmet need for novel analytical tools providing unbiased quantitative measurements of NP disassembly directly in the medium of interest and in conditions relevant to specific therapeutic/diagnostic applications. In the present study, this challenge was addressed with an approach enabling real-time in situ monitoring of the integrity status of NPs in cells and biomimetic media using Förster resonance energy transfer (FRET). Disassembly of polylactide-based magnetic NPs (MNPs) was investigated in a range of model biomimetic media and in cultured vascular cells using an experimentally established quantitative correlation between particle integrity and FRET efficiency controlled through adjustments in the spectral overlap between two custom-synthesized polylactide-fluorophore (boron dipyrromethene) conjugates incorporated in MNPs. The results suggest particle disassembly governed by diffusion-reaction processes with kinetics strongly dependent on conditions promoting release of oligomeric fragments from the particle matrix. Thus, incubation in gels simulating the extracellular environment and in protein-rich serum resulted in notably lower and higher MNP decomposition rates, respectively, compared with nonviscous liquid buffers. The diffusion-reaction mechanism also is consistent with a significant cell growth-dependent acceleration of MNP processing in dividing vs. contact-inhibited vascular cells. The FRET-based analytical strategy and experimental results reported herein may facilitate the development and inform optimization of biodegradable nanocarriers for cell and drug delivery applications.
authors.affiliation: Division of Cardiology Research, The Children's Hospital of Philadelphia, Philadelphia, PA 19104.
authors.forename: Jillian E
authors.initials: JE
authors.lastname: Tengood
authors.forename: Ivan S
authors.initials: IS
authors.lastname: Alferiev
authors.forename: Kehan
authors.initials: K
authors.lastname: Zhang
authors.forename: Ilia
authors.initials: I
authors.lastname: Fishbein
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Levy
authors.forename: Michael
authors.initials: M
authors.lastname: Chorny
mesh_terms: D000704:Analysis of Variance; D040761:Biomimetic Materials / Q000032:analysis*; D001808:Blood Vessels / Q000166:cytology; D003199:Computer Systems; D004337:Drug Carriers / Q000737:chemistry*; D031541:Fluorescence Resonance Energy Transfer; D058185:Magnetite Nanoparticles / Q000737:chemistry* / Q000627:therapeutic use; D008422:Materials Testing / Q000379:methods*
chemical_list: D004337:Drug Carriers; D058185:Magnetite Nanoparticles
keywords: direct assay; endothelial cell; nanoparticle degradation; restenosis; smooth muscle cell