title: Working together: the combined application of a magnetic field and penetratin for the delivery of magnetic nanoparticles to cells in 3D.
abstract: Nanoparticles (NPs) are currently being developed as vehicles for in vivo drug delivery. Two of the biggest barriers facing this therapy are the site-specific targeting and consequent cellular uptake of drug-loaded NPs(1). In vitro studies in 2D cell cultures have shown that an external magnetic field (MF) and functionalization with cell-penetrating peptides (CPPs) have the capacity to overcome these barriers. This study aimed to investigate if the potential of these techniques, which has been reported in 2D, can be successfully applied to cells growing in a 3D environment. As such, this study provides a more realistic assessment of how these techniques might perform in future clinical settings. The effect of a MF and/or penetratin attachment on the uptake of 100 and 200 nm fluorescent iron oxide magnetic NPs (mNPs) into a fibroblast-seeded 3D collagen gel was quantified by inductively coupled plasma mass spectrometry. The most suitable mNP species was further investigated by fluorescence microscopy, histology, confocal microscopy, and TEM. Results show that gel mNP uptake occurred on average twice as fast in the presence of a MF and up to three times faster with penetratin attachment. In addition, a MF increased the distance of mNP travel through the gel, while penetratin increased mNP cell localization. This work is one of the first to demonstrate that MFs and CPPs can be effectively translated for use in 3D systems and, if applied together, will make excellent partners to achieve therapeutic drug delivery in vivo.
authors: Centre for Cell Engineering, Glasgow University, Joseph Black Building, G12 8QQ, U.K.
authors: Hannah W
authors: HW
authors: Child
authors: Pablo A
authors: PA
authors: Del Pino
authors: Jesus M
authors: JM
authors: De La Fuente
authors: Andrew S
authors: AS
authors: Hursthouse
authors: David
authors: D
authors: Stirling
authors: Margaret
authors: M
authors: Mullen
authors: Gordon M
authors: GM
authors: McPhee
authors: Colin
authors: C
authors: Nixon
authors: Vineetha
authors: V
authors: Jayawarna
authors: Catherine C
authors: CC
authors: Berry
mesh_terms: D001692:Biological Transport; D002352:Carrier Proteins / Q000737:chemistry*; D018929:Cell Culture Techniques / Q000379:methods*; D057846:Cell-Penetrating Peptides; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D005290:Ferric Compounds / Q000737:chemistry*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006801:Humans; D060526:Magnetic Fields; D013058:Mass Spectrometry; D008853:Microscopy; D053758:Nanoparticles / Q000737:chemistry*; D012212:Rheology
chemical_list: D002352:Carrier Proteins; D057846:Cell-Penetrating Peptides; D004337:Drug Carriers; D005290:Ferric Compounds; C000499:ferric oxide; C414409:penetratin