Mesangial cells represent one third of all cells in the glomerulus, where they build up the central stalk and regulate the turnover of the mesangial matrix [1]. Lately, mesangial cells emerged as an interesting target for drug delivery with nanoparticles because of their tremendous contribution to the pathogenesis of several glomerular diseases like diabetic or IgA nephropathy. In addition, mesangial cells can be passively targeted with nanoparticles smaller than 100 nm. This is possible due to the size of the endothelial fenestrations they are located behind [2]. Here we want to show a ligand-mediated targeting of rat mesangial cells with quantum dots (Qdots) coupled to angiotensin II, the physiological receptor agonist of the angiotensin II receptor type 1 (AT1).Amine-terminated Qdots were covalently labeled with an N-terminal thiolated angiotensin II derivative using the heterobifunctional linker sulfo-SMCC. To show that mesangial cells express a functional Gq-coupled AT1 receptor, intracellular calcium measurements were conducted using Fura-2AM. Angiotensin II itself as well as the modified Qdots displayed a strong intracellular calcium signal. In flow cytometry experiments the angiotensin II-modified Qdots exhibited a high binding to the mesangial cells that was displaceable with the AT1 receptor antagonist EXP3174. The binding of these ligand-coupled nanoparticles to receptor-negative cell lines was negligible. Additionally, confocal laser scanning microscopy revealed the uptake of the modified Qdots into vesicle-like structures, which is a prerequisite for nanoparticle delivery to cells. In conclusion we could show that ligand-modified Qdots can be used to target mesangial cells in vitro. The nanoparticles specifically bind the AT1 receptor and are taken up by the cells whereas off-target cells do not interact with the Qdots.[1] D. Schl�ndorff et al., J. Am. Soc. Nephrol., 2009, 6, 1179�1187[2] C.H. Choi et al., Proc. Natl. Acad. Sci. U.S.A., 2011, 16, 6656�6661

Targeting of mesangial cells with ligand-conjugated quantum dots

246th National Meeting (2013)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.