2 research outputs found
Synthesis of Polymer–Lipid Nanoparticles for Image-Guided Delivery of Dual Modality Therapy
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-<i>co</i>-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
Near-Infrared Fluorescence Energy Transfer Imaging of Nanoparticle Accumulation and Dissociation Kinetics in Tumor-Bearing Mice
In the current study we show the dissociation and tumor accumulation dynamics of dual-labeled near-infrared quantum dot core self-assembled lipidic nanoparticles (SALNPs) in a mouse model upon intravenous administration. Using advanced <i>in vivo</i> fluorescence energy transfer imaging techniques, we observed swift exchange with plasma protein components in the blood and progressive SALNP dissociation and subsequent trafficking of individual SALNP components following tumor accumulation. Our results suggest that upon intravenous administration SALNPs quickly transform, which may affect their functionality. The presented technology provides a modular <i>in vivo</i> tool to visualize SALNP behavior in real time and may contribute to improving the therapeutic outcome or molecular imaging signature of SALNPs