Melanoma and lymphocyte cell-specific targeting incorporated into a heat shock protein cage architecture.
Protein cages, including viral capsids, ferritins, and heat shock proteins (Hsps), can serve as nanocontainers for biomedical applications. They are genetically and chemically malleable platforms, with potential as therapeutic and imaging agent delivery systems. Here, both genetic and chemical strategies were used to impart cell-specific targeting to the Hsp cage from Methanococcus jannaschii. A tumor vasculature targeting peptide was incorporated onto the exterior surface of the Hsp cage. This protein cage bound to alpha(v)beta(3) integrin-expressing cells. Cellular tropism was also imparted by conjugating anti-CD4 antibodies to the exterior of Hsp cages. These Ab-Hsp cage conjugates specifically bound to CD4(+) cells. Protein cages have the potential to simultaneously incorporate multiple functionalities, including cell-specific targeting, imaging, and therapeutic agent delivery. We demonstrate the simultaneous incorporation of two functionalities, imaging and cell-specific targeting, onto the Hsp protein cage.
Department of Microbiology, Montana State University, Gaines Hall, Bozeman, 59717, USA.
Michelle L
ML
Flenniken
Deborah A
DA
Willits
Ann L
AL
Harmsen
Lars O
LO
Liepold
Allen G
AG
Harmsen
Mark J
MJ
Young
Trevor
T
Douglas
D000818:Animals; D001483:Base Sequence; D015704:CD4 Antigens / Q000276:immunology; D002469:Cell Separation; D002478:Cells, Cultured; D017931:DNA Primers; D004591:Electrophoresis, Polyacrylamide Gel; D005434:Flow Cytometry; D006360:Heat-Shock Proteins / Q000737:chemistry*; D008214:Lymphocytes / Q000166:cytology*; D008545:Melanoma / Q000473:pathology*; D017017:Methanococcus / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence; D036103:Nanotechnology
D015704:CD4 Antigens; D017931:DNA Primers; D006360:Heat-Shock Proteins