Dendrimeric Guanidinoneomycin for Cellular Delivery of Bio-macromolecules.
We present the synthesis of polymeric amino- and guanidinoglycosides prepared by tethering neomycin and guanidinoneomycin to PAMAM dendrimers of generations 2 and 4. The ability of these conjugates to promote cellular uptake of high-molecular-weight cargo is discussed, together with their cytotoxicity and mechanisms of entry. We demonstrate that the presence of multiple guanidinoneomycin carriers on the PAMAM surface plays an important role in promoting cellular uptake of the dendrimers, maintaining the heparan sulfate specificity and negligible cytotoxicity typical of monomeric guanidinoglycoside molecular transporters.
Department of Chemistry, Material and Chemical Engineering "Giulio Natta", Politecnico di Milano, via Mancinelli 7, 20131, Milano, Italy.
Aurora
A
Sganappa
Department of Chemistry and Biochemistry, University of California, 9500 Gilman Drive, La Jolla, CA, 92093, USA.
Ezequiel
E
Wexselblatt
Department of Food, Environmental and Nutritional Sciences, Università degli Studi di Milano, Via Celoria 2, 20133 Milano, Italy.
Maria Cristina
MC
Bellucci
Department of Cellular and Molecular Medicine, University of California, 9500 Gilman Drive, La Jolla, CA, 92093, USA.
Jeffrey D
JD
Esko
Department of Veterinary Science and Public Health, Università degli Studi di Milano, Via Celoria 2, 20133, Milano, Italy.
Gabriella
G
Tedeschi
Department of Chemistry and Biochemistry, University of California, 9500 Gilman Drive, La Jolla, CA, 92093, USA.
Yitzhak
Y
Tor
Department of Chemistry, Material and Chemical Engineering "Giulio Natta", Politecnico di Milano, via Mancinelli 7, 20131, Milano, Italy.
Alessandro
http://orcid.org/0000-0002-0125-0744
A
Volonterio
D000617:Aminoglycosides / Q000737:chemistry*; D000818:Animals; D001710:Biotin / Q000737:chemistry; D016466:CHO Cells; D002232:Carbocyanines / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D050091:Dendrimers / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry* / Q000494:pharmacology / Q000633:toxicity; D004705:Endocytosis / Q000187:drug effects
D000617:Aminoglycosides; D002232:Carbocyanines; D050091:Dendrimers; D004337:Drug Carriers; C104700:PAMAM Starburst; C085321:cyanine dye 5; C526745:guanidinoneomycin B; D001710:Biotin
PAMAM; cellular uptake; dendrimers; drug delivery; guanidinium-rich transporters; guanidinoglycosides