Kidney podocytes as specific targets for cyclo(RGDfC)-modified nanoparticles.
Renal nanoparticle passage opens the door for targeting new cells like podocytes, which constitute the exterior part of the renal filter. When cyclo(RGDfC)-modified Qdots are tested on isolated primary podocytes for selective binding to the αvβ3 integrin receptor a highly cell- and receptor-specific binding can be observed. In displacement experiments with free cyclo(RGDfC) IC(50)  values of 150 nM for αvβ3 integrin over-expressing U87-MG cells and 60 nM for podocytes are measured. Confocal microscopy shows a cellular Qdot uptake into vesicle-like structures. Our ex vivo study gives clear evidence that, after renal filtration, nanoparticles can be targeted to podocyte integrin receptors in the future. This could be a highly promising approach for future therapy and diagnostics of podocyte-associated diseases.
Department of Pharmaceutical Technology, University of Regensburg, Universitätsstr. 31, 93053 Regensburg, Germany.
Klaus
K
Pollinger
Robert
R
Hennig
Miriam
M
Breunig
Joerg
J
Tessmar
Andreas
A
Ohlmann
Ernst R
ER
Tamm
Ralph
R
Witzgall
Achim
A
Goepferich
D000818:Animals; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D007668:Kidney / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010456:Peptides, Cyclic / Q000494:pharmacology*; D050199:Podocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000737:chemistry; D045663:Quantum Dots
D039302:Integrin alphaVbeta3; D010456:Peptides, Cyclic; C507169:cyclic arginine-glycine-aspartic acid peptide; C583418:cyclo(arginyl-glycyl-aspartyl-phenylalanyl-cysteinyl); D011092:Polyethylene Glycols