Targeting of Cancer Cells Using Quantum Dot-Polypeptide Hybrid Assemblies that Function as Molecular Imaging Agents and Carrier Systems.
We report a highly tunable quantum dot (QD)-polypeptide hybrid assembly system with potential uses for both molecular imaging and delivery of biomolecular cargo to cancer cells. In this work, we demonstrate the tunability of the assembly system, its application for imaging cancer cells, and its ability to carry a biomolecule. The assemblies are formed through the self-assembly of carboxyl-functionalized QDs and poly(diethylene glycol-L-lysine)-poly(L-lysine) (PEGLL-PLL) diblock copolypeptide molecules, and they are modified with peptide ligands containing a cyclic arginine-glycine-aspartate [c(RGD)] motif that has affinity for αvβ3and αvβ5integrins overexpressed on the tumor vasculature. To illustrate the tunability of the QD-polypeptide assembly system, we show that binding to U87MG glioblastoma cells can be modulated and optimized by changing either the conditions under which the assemblies are formed or the relative lengths of the PEGLL and PLL blocks in the PEGLL-PLL molecules. The optimized c(RGD)-modified assemblies bind integrin receptors on U87MG cells and are endocytosed, as demonstrated by flow cytometry and live-cell imaging. Binding specificity is confirmed by competition with an excess of free c(RGD) peptide. Finally, we show that the QD-polypeptide assemblies can be loaded with fluorescently labeled ovalbumin, as a proof-of-concept for their potential use in biomolecule delivery.
Department of Chemical Engineering, Stanford University, 381 North-South Mall, Stauffer III, Stanford, CA 94305. U.S.A.
Bayu
B
Atmaja
Department of Bioengineering, Stanford University, The James H. Clark Center, W250, Stanford, CA 94305. U.S.A.
Bertrand H
BH
Lui
Department of Chemical Engineering, Stanford University, 381 North-South Mall, Stauffer III, Stanford, CA 94305. U.S.A.
Yuhua
Y
Hu
DMA/OBP/CDER/FDA.
Stayce E
SE
Beck
Department of Chemical Engineering, Stanford University, 381 North-South Mall, Stauffer III, Stanford, CA 94305. U.S.A.
Curtis W
CW
Frank
Department of Bioengineering, Stanford University, The James H. Clark Center, W250, Stanford, CA 94305. U.S.A ; Department of Bioengineering, Stanford University, The James H. Clark Center, W250, Stanford, CA 94305. U.S.A.
Jennifer R
JR
Cochran
hybrid materials; nanostructures; quantum dots; self-assembly; supramolecular materials