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Formulation and In Vitro Characterization of Composite Biodegradable Magnetic Nanoparticles for Magnetically Guided Cell Delivery

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ABSTRACT

Purpose

Cells modified with magnetically responsive nanoparticles (MNP) can provide the basis for novel targeted therapeutic strategies. However, improvements are required in the MNP design and cell treatment protocols to provide adequate magnetic properties in balance with acceptable cell viability and function. This study focused on select variables controlling the uptake and cell compatibility of biodegradable polymer-based MNP in cultured endothelial cells.

Methods

Fluorescent-labeled MNP were formed using magnetite and polylactide as structural components. Their magnetically driven sedimentation and uptake were studied fluorimetrically relative to cell viability in comparison to non-magnetic control conditions. The utility of surface-activated MNP forming affinity complexes with replication-deficient adenovirus (Ad) for transduction achieved concomitantly with magnetic cell loading was examined using the green fluorescent protein reporter.

Results

A high-gradient magnetic field was essential for sedimentation and cell binding of albumin-stabilized MNP, the latter being rate-limiting in the MNP loading process. Cell loading up to 160 pg iron oxide per cell was achievable with cell viability >90%. Magnetically driven uptake of MNP-Ad complexes can provide high levels of transgene expression potentially useful for a combined cell/gene therapy.

Conclusions

Magnetically responsive endothelial cells for targeted delivery applications can be obtained rapidly and efficiently using composite biodegradable MNP.

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Abbreviations

Ad:

adenovirus

BAEC:

bovine aortic endothelial cells

BSA:

bovine serum albumin

CAR:

Coxsackie-adenovirus receptor

CMV:

cytomegalovirus

DCC:

1,3-dicyclohexylcarbodiimide

DMEM:

Dulbecco’s modification of Eagle’s medium

EDC:

1-ethyl-3-(3-dimethylaminopropyl)carbodiimide

FBS:

fetal bovine serum

GFP:

green fluorescent protein

MNP:

magnetic nanoparticle

PBS:

phosphate buffered saline

PLA:

polylactide

SPDP:

N-succinimidyl 3-(2-pyridyldithio)propionate

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ACKNOWLEDGMENTS & DISCLOSURES

This research was supported in part by grants from the NIH (HL72108 and HL94816), the American Heart Association (Scientist Development Grant 10SDG4020003), the Nanotechnology Institute and the William J. Rashkind Endowment of The Children’s Hospital of Philadelphia.

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Authors and Affiliations

  1. Division of Cardiology, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, 19104, USA

    Michael Chorny, Ivan S. Alferiev, Ilia Fishbein, Jillian E. Tengood, Zoë Folchman-Wagner, Scott P. Forbes & Robert J. Levy

  2. The Children’s Hospital of Philadelphia, Abramson Research Building Suite 702 G, 3615 Civic Center Boulevard, Philadelphia, Pennsylvania, 19104-4318, USA

    Michael Chorny

Authors
  1. Michael Chorny
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  2. Ivan S. Alferiev
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  3. Ilia Fishbein
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  4. Jillian E. Tengood
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  5. Zoë Folchman-Wagner
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  6. Scott P. Forbes
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  7. Robert J. Levy
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Correspondence to Michael Chorny.

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Chorny, M., Alferiev, I.S., Fishbein, I. et al. Formulation and In Vitro Characterization of Composite Biodegradable Magnetic Nanoparticles for Magnetically Guided Cell Delivery. Pharm Res 29, 1232–1241 (2012). https://doi.org/10.1007/s11095-012-0675-y

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  • DOI: https://doi.org/10.1007/s11095-012-0675-y

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