PAMAM-RGD conjugates enhance siRNA delivery through a multicellular spheroid model of malignant glioma.
Generation 5 poly(amidoamine) (PAMAM) dendrimers were modified by the addition of cyclic RGD targeting peptides and were evaluated for their ability to associate with siRNA and mediate siRNA delivery to U87 malignant glioma cells. PAMAM-RGD conjugates were able to complex with siRNA to form complexes of approximately 200 nm in size. Modest siRNA delivery was observed in U87 cells using either PAMAM or PAMAM-RGD conjugates. PAMAM-RGD conjugates prevented the adhesion of U87 cells to fibrinogen-coated plates, in a manner that depends on the number of RGD ligands per dendrimer. The delivery of siRNA through three-dimensional multicellular spheroids of U87 cells was enhanced using PAMAM-RGD conjugates compared to the native PAMAM dendrimers, presumably by interfering with integrin-ECM contacts present in a three-dimensional tumor model.
Department of Chemical and Biochemical Engineering and Department of Biomedical Engineering, Rutgers University, 599 Taylor Road, Piscataway, NJ 08854, USA.
Carolyn L
CL
Waite
Charles M
CM
Roth
D045744:Cell Line, Tumor; D050091:Dendrimers / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods*; D016326:Extracellular Matrix Proteins / Q000037:antagonists & inhibitors; D005910:Glioma / Q000188:drug therapy; D006801:Humans; D016023:Integrins / Q000037:antagonists & inhibitors; D008958:Models, Molecular; D010456:Peptides, Cyclic / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D018874:Spheroids, Cellular / Q000737:chemistry* / Q000378:metabolism*
D050091:Dendrimers; D016326:Extracellular Matrix Proteins; D016023:Integrins; C104700:PAMAM Starburst; D010456:Peptides, Cyclic; D034741:RNA, Small Interfering; C507169:cyclic arginine-glycine-aspartic acid peptide