Targeted Tumor Cell Internalization and Imaging of Multifunctional Quantum Dot-Conjugated Immunoliposomes in Vitro and in Vivo

• Published in: Nano letters Vol. 8; no. 9; pp. 2851 - 2857
• Main Authors: Weng, Kevin C, Noble, Charles O, Papahadjopoulos-Sternberg, Brigitte, Chen, Fanqing F, Drummond, Daryl C, Kirpotin, Dmitri B, Wang, Donghui, Hom, Yun K, Hann, Byron, Park, John W
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 01.09.2008
• Subjects: Animals; Applied sciences; Cell Line, Tumor; Condensed matter: electronic structure, electrical, magnetic, and optical properties; Cross-disciplinary physics: materials science; rheology; Electronics; Exact sciences and technology; Freeze Fracturing; Humans; Liposomes; Materials science; Mice; Microscopy, Electron; Molecular electronics, nanoelectronics; Nanocrystalline materials; Nanoscale materials and structures: fabrication and characterization; Optical properties and condensed-matter spectroscopy and other interactions of matter with particles and radiation; Optical properties of low-dimensional, mesoscopic, and nanoscale materials and structures; Physics; Quantum Dots; Semiconductor electronics. Microelectronics. Optoelectronics. Solid state devices; Drug delivery systems; Tumor cells; Quantum dots; Fluorescence; Cytotoxicity; Confocal microscopy; Drug carrier; Electron microscopy; Potassium alloys; Nanoparticles; In vivo; Endocytosis; Fractures; Tumours; Imaging; Targeted drug; Optical properties; Nanostructured materials; Medical application; Sodium alloys
• ISSN: 1530-6984; 1530-6992
• DOI: 10.1021/nl801488u

Targeted drug delivery systems that combine imaging and therapeutic modalities in a single macromolecular construct may offer advantages in the development and application of nanomedicines. To incorporate the unique optical properties of luminescent quantum dots (QDs) into immunoliposomes for cancer diagnosis and treatment, we describe the synthesis, biophysical characterization, tumor cell-selective internalization, and anticancer drug delivery of QD-conjugated immunoliposome-based nanoparticles (QD-ILs). Pharmacokinetic properties and in vivo imaging capability of QD-ILs were also investigated. Freeze-fracture electron microscopy was used to visualize naked QDs, liposome controls, nontargeted QD-conjugated liposomes (QD-Ls), and QD-ILs. QD-ILs prepared by insertion of anti-HER2 scFv exhibited efficient receptor-mediated endocytosis in HER2-overexpressing SK-BR-3 and MCF-7/HER2 cells but not in control MCF-7 cells as analyzed by flow cytometry and confocal microscopy. In contrast, nontargeted QD-Ls showed minimal binding and uptake in these cells. Doxorubicin-loaded QD-ILs showed efficient anticancer activity, while no cytotoxicity was observed for QD-ILs without chemotherapeutic payload. In athymic mice, QD-ILs significantly prolonged circulation of QDs, exhibiting a plasma terminal half-life (t 1/2) of ∼2.9 h as compared to free QDs with t 1/2 < 10 min. In MCF-7/HER2 xenograft models, localization of QD-ILs at tumor sites was confirmed by in vivo fluorescence imaging.