RNAi-based glyconanoparticles trigger apoptotic pathways for in vitro and in vivo enhanced cancer-cell killing.
Gold glyconanoparticles (GlycoNPs) are full of promise in areas like biomedicine, biotechnology and materials science due to their amazing physical, chemical and biological properties. Here, siRNA GlycoNPs (AuNP@PEG@Glucose@siRNA) in comparison with PEGylated GlycoNPs (AuNP@PEG@Glucose) were applied in vitro to a luciferase-CMT/167 adenocarcinoma cancer cell line and in vivo via intratracheal instillation directly into the lungs of B6 albino mice grafted with luciferase-CMT/167 adenocarcinoma cells. siRNA GlycoNPs but not PEGylated GlycoNPs induced the expression of pro-apoptotic proteins such as Fas/CD95 and caspases 3 and 9 in CMT/167 adenocarcinoma cells in a dose dependent manner, independent of the inflammatory response, evaluated by bronchoalveolar lavage cell counting. Moreover, in vivo pulmonary delivered siRNA GlycoNPs were capable of targeting c-Myc gene expression (a crucial regulator of cell proliferation and apoptosis) via in vivo RNAi in tumour tissue, leading to an ∼80% reduction in tumour size without associated inflammation.
Massachusetts Institute of Technology, Institute for Medical Engineering and Science, Harvard-MIT Division for Health Sciences and Technology, E25-449 Cambridge, Massachusetts, USA.
João
J
Conde
Furong
F
Tian
Yulan
Y
Hernandez
Chenchen
C
Bao
Pedro V
PV
Baptista
Daxiang
D
Cui
Tobias
T
Stoeger
Jesus M
JM
de la Fuente
D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D005947:Glucose / Q000737:chemistry*; D006046:Gold / Q000737:chemistry; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D053768:Metal Nanoparticles / Q000737:chemistry*; D051379:Mice; D061848:Optical Imaging; D011092:Polyethylene Glycols / Q000737:chemistry; D016271:Proto-Oncogene Proteins c-myc / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000737:chemistry / Q000378:metabolism*; D014057:Tomography, X-Ray Computed; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism
D016271:Proto-Oncogene Proteins c-myc; D034741:RNA, Small Interfering; D019014:fas Receptor; D011092:Polyethylene Glycols; D006046:Gold; D005947:Glucose