Synthesis of Polymer鈥揕ipid Nanoparticles for Image-Guided Delivery of Dual Modality Therapy

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• 作者：Aneta J. Mieszawska ; YongTae Kim ; Anita Gianella ; Inge van Rooy ; Bram Priem ; Matthew P. Labarre ; Canturk Ozcan ; David P. Cormode ; Artiom Petrov ; Robert Langer ; Omid C. Farokhzad ; Zahi A. Fayad ; Willem J. M. Mulder
• 刊名：Bioconjugate Chemistry
• 出版年：2013
• 出版时间：September 18, 2013
• 年：2013
• 卷：24
• 期：9
• 页码：1429-1434
• 全文大小：335K
• 年卷期：v.24,no.9(September 18, 2013)
• ISSN：1520-4812

文摘

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鈥搇ipid 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.