Doxorubicin-loaded and antibody-conjugated liposome-QD hybrid vesicles for targeted cancer therapy and imaging

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Quantum dots (QD) have been extensively explored for in vitro and in vivo imaging due to their superior fluorescence properties compared to organic fluorophores. The hydrophobic nature of QD hinders their biomedical applications in biological milieu, therefore many efforts have been made to construct water-soluble QD by substituting the organic surface ligands with hydrophilic moieties. However such surface modifications adversely affected the QD optical properties and colloidal stability. Previously, our group offered an alternative approach to improve QD hydrophilicity by incorporating hydrophobic QD into liposome lipid bilayer (L-QD) which efficiently labelled cancer cells in vitro and in vivo. In this study, we report the engineering of multimodal liposome-QD hybrids (L-QD) for cancer imaging and therapy. L-QD hybrids were loaded with Dox using the osmotic gradient technique, achieving high encapsulation efficiency comparable to liposome alone. Structural elucidation using cryogenic electron microscopy (cryo-EM) clearly showed that QD were incorporated in the lipid bilayer and Dox crystals were encapsulated into the liposome aqueous core. Furthermore, the surface of Dox-loaded hybrids were functionalized with anti-MUC-1 antibody for active targeting, using the post-insertion technique. The specific binding of antibody-targeted hybrids was studied against the MUC1 epitope by surface plasmon resonance (BIACORE) showing higher binding affinity than the antibody alone due to a multivalent effect. In addition, cellular uptake studies of the antibody-targeted hybrids were conducted using confocal laser scanning microscopy (CLSM). The antibody-targeted hybrids showed high binding and uptake by human breast cancer cells (MCF-7) that overexpress MUC-1 receptors in contrast to human pulmonary adenocarcinoma cells (Calu-6) exhibiting low level of MUC-1 expression. Finally, cytotoxicity assays indicated higher toxicity of antibody-targeted hybrids in MCF-7 compared to Calu-6 cells. In conclusion, MUC-1 antibody-targeted L-QD hybrids encapsulating doxorubicin are thought to constitute a potential multimodal system for the simultaneous delivery of therapeutic and diagnostic agents to cancer cells in vitro and in vivo.

Bibliographical metadata

Original languageEnglish
Title of host publicationNanotechnology 2010: Technical Proceedings of the 2010 NSTI Nanotechnology Conference and Expo, NSTI-Nanotech 2010
Place of PublicationBoca Raton
PublisherCRC Press
Pages380-381
Number of pages1
Volume3-Bio Sensors, Instruments, Medical, Environment and Energy
ISBN (Print)9781439834152
Publication statusPublished - 2010