Title
Thermo-Responsive Collagen/Cell Penetrating Hybrid Peptide as Nanocarrier in Targeting-Free Cell Selection and Uptake
Author
Myungeun Oh, Chloe Hu, Selina F Urfano, Merlyn Arostegui, Katarzyna Slowinska
Year
2016
Journal
Analytical Chemistry
Abstract
The effective delivery of therapeutics and imaging agents to a selected group of cells has been at the forefront of biomedical research. Unfortunately, the identification of the unique cell surface targets for cell selection remains a major challenge, particularly if cells within the selected group are not identical. Here we demonstrate a novel approach to cell section relying on a thermo-responsive peptide-based nanocarrier. The hybrid peptide containing cell-penetrating peptide (CPP) and collagen (COLL) domains is designed to undergo coil-to-helix transition (folding) below physiological temperature. Since only helical form undergoes effective internalization by the cells, this approach allows effective temperature-discriminate cellular uptake. The cells selected for uptake are locally cooled down thus enabling the carrier to fold and subsequently internalize. Our approach demonstrates a generic method as selected cells could differ from the adjacent cells or could belong to the same cell population. The method is fast (< 15 min) and selective; over 99.6% of cells in vitro internalized the peptide carrier at low temperatures (15°C), while less than 0.2% internalized at 37°C. In vivo results confirm the high selectivity of the method. The potential clinical applications in mixed cell differentiation carcinoma, most frequently encountered in breast and ovarian cancer, are envisioned.
Instrument
J-810
Keywords
Circular dichroism, Secondary structure, Thermal stability, Nanostructures, Materials, Biochemistry