Synthesis of Polymer–Lipid Nanoparticles for Image-Guided Delivery of Dual Modality Therapy
Name
nihms-518046.pdf
Description
Accepted version
Size
1.92 MB
Format
Adobe PDF
Checksum (MD5)
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Author(s)
Mieszawska, Aneta J
Kim, YongTae
Gianella, Anita
van Rooy, Inge
Priem, Bram
Labarre, Matthew P
Ozcan, Canturk
Cormode, David P
Petrov, Artiom
Langer, Robert
Date Issued
2013
Journal
Bioconjugate Chemistry
Publisher
American Chemical Society (ACS)
Citation
Mieszawska, A. J., et al. "Synthesis of Polymer-Lipid Nanoparticles for Image-Guided Delivery of Dual Modality Therapy." Bioconjugate Chemistry 24 9 (2013): 1429-34.
Version
Author's final manuscript
Abstract
For advanced treatment of diseases such as cancer, multicomponent, multifunctional nanoparticles hold great promise. In the current study we report the synthesis of a complex nanoparticle (NP) system with dual drug loading as well as diagnostic properties. To that aim we present a methodology where chemically modified poly(lactic-co-glycolic) acid (PLGA) polymer is formulated into a polymer-lipid NP that contains a cytotoxic drug doxorubicin (DOX) in the polymeric core and an anti-angiogenic drug sorafenib (SRF) in the lipidic corona. The NP core also contains gold nanocrystals (AuNCs) for imaging purposes and cyclodextrin molecules to maximize the DOX encapsulation in the NP core. In addition, a near-infrared (NIR) Cy7 dye was incorporated in the coating. To fabricate the NP we used a microfluidics-based technique that offers unique NP synthesis conditions, which allowed for encapsulation and fine-tuning of optimal ratios of all the NP components. NP phantoms could be visualized with computed tomography (CT) and near-infrared (NIR) fluorescence imaging. We observed timed release of the encapsulated drugs, with fast release of the corona drug SRF and delayed release of a core drug DOX. In tumor bearing mice intravenously administered NPs were found to accumulate at the tumor site by fluorescence imaging. © 2013 American Chemical Society.
MIT Department
Koch Institute for Integrative Cancer Research at MIT
Massachusetts Institute of Technology. Department of Chemical Engineering
Harvard University--MIT Division of Health Sciences and Technology
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DOI of Published Version
https://doi.org/10.1021/BC400166J
