Controllable self-assembly of nanoparticles for specific delivery of multiple therapeutic molecules to cancer cells using RNA nanotechnology.
By utilizing RNA nanotechnology, we engineered both therapeutic siRNA and a receptor-binding RNA aptamer into individual pRNAs of phi29's motor. The RNA building block harboring siRNA or other therapeutic molecules was fabricated subsequently into a trimer through the interaction of engineered right and left interlocking RNA loops. The incubation of the protein-free nanoscale particles containing the receptor-binding aptamer or other ligands resulted in the binding and co-entry of the trivalent therapeutic particles into cells, subsequently modulating the apoptosis of cancer cells and leukemia model lymphocytes in cell culture and animal trials. The use of such antigenicity-free 20-40 nm particles holds promise for the repeated long-term treatment of chronic diseases.
Khaled
Annette
A
Department of Pathobiology and Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana 47907, USA.
Guo
Songchuan
S
Li
Feng
F
Guo
Peixuan
P
D000818:Animals; D001483:Base Sequence; D015704:CD4 Antigens / Q000235:genetics; D045744:Cell Line, Tumor; D005818:Genetic Engineering; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008958:Models, Molecular; D049329:Nanostructures / Q000737:chemistry; D036103:Nanotechnology / Q000379:methods*; D009369:Neoplasms / Q000628:therapy; D009374:Neoplasms, Experimental / Q000235:genetics / Q000628:therapy*; D009690:Nucleic Acid Conformation; D012313:RNA / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics
D015704:CD4 Antigens; D034741:RNA, Small Interfering; D012313:RNA