Synthesis of Polymer–Lipid Nanoparticles for Image-Guided Delivery of Dual Modality Therapy

Abstract

For advanced treatment of diseases such as cancer, multi component, multi functional 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.