2007 NSTI Nanotechnology Conference and Trade Show - Nanotech 2007 - 10th Annual

Optimizing Quantum Dot-Conjugated Immunoliposomes for Cancer Diagnostics and Targeted Therapeutics

K.C. Weng, C.O. Noble, B. Papahadjopoulos-Sternberg, F.F. Chen and J.W. Park
UCSF Comprehensive Cancer Center, US

Keywords:
quantum dots, immunoliposomes, nanomedicine, anti-HER2, targeted drug delivery systems

Abstract:
A multifunctional nanoparticle that combines the optical properties of luminescent quantum dots (QDs) and therapeutic modality of immunoliposomes (ILs) has been developed. Carboxylate-derivatized QDs cross-linked with amino- poly(ethylene glycol)-functionalized liposomes were modified with anti-human epidermal growth factor receptor 2 (anti- HER2) scFv, resulting in quantum dot-conjugated immunoliposomes (QD-ILs). QD-ILs exhibited highly efficient and specific internalization by HER2-overexpressing tumor cells and facilitated long-term tracking of the drug delivery systems in vitro. However, reduced uptake and increased cell surface binding were observed for some aggregated, bulkier QD-ILs. To use QD-ILs for in vivo applications, a thorough understanding of the physical properties of the nanocomplex is necessary. A systematic investigation on how the synthesis parameters, particularly the ratios of various reagents and building components, affect the geometry, degree of crosslinking, and the interactions of resulting nanostructures with cells is reported in this study. Flow cytometry is used to quantitate the amount of cellular uptake while spatial distributions of QD-ILs within the cellular matrix are determined by confocal microscopy. Freeze-fracture electron microscopy and dynamic light scattering are used to characterize the morphology and size of nanostructures. The study also provides guidelines for the design of nanomedicine from the perspective of cellular interactions.

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