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Synthesis of Polymer–Lipid Nanoparticles for Image-Guided Delivery of Dual Modality Therapy
Authors
David P Cormode
Omid C Farokhzad
+11 more
Zahi A Fayad
Anita Gianella
YongTae Kim
Matthew P Labarre
Robert Langer
Aneta J Mieszawska
Willem JM Mulder
Canturk Ozcan
Artiom Petrov
Bram Priem
Inge van Rooy
Publication date
5 September 2019
Publisher
'American Chemical Society (ACS)'
Doi
Cite
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
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Last time updated on 19/12/2021