Combined multimodal optical imaging and targeted gene silencing using stimuli-transforming nanotheragnostics.
Combined diagnosis and therapy for cancer has been of great interest in medicine. Small interference RNA (siRNA)-encapsulating polyplexes were covalently coated with small gold nanoparticles (Au NPs) via acid-cleavable linkages in order to explore the possibility of achieving combined stimuli-responsive multimodal optical imaging and stimuli-enhanced gene silencing. In a mildly acidic tumor environment, Au NPs are dissociated from the siRNA-carrying polyplexes, generating various optical signal changes such as diminished scattering intensity, increased variance of Doppler frequency, and blue-shifted UV absorbance (stimuli-responsive imaging). Simultaneously, Au NP dissociation exposes the siRNA-carrying polyplex with elevated surface charge and results in enhanced cellular uptake and transfection (stimuli-enhanced therapy). In this study, the feasibility of achieving combined diagnosis and therapy for cancer (theragnostics) is demonstrated by (1) microscopic and spectrophotometric confirmation of acid-transformation of the nanoparticles, (2) reduced scattering intensity and increased variance of Doppler frequency in an acidic pH upon the nanoparticle's transformation, and (3) simultaneous optical signal changes and gene silencing in vitro under a tumor pH-mimicking condition. This novel type of stimuli-responsive nanotheragnostics will provide a new paradigm for pinpointed, multimodal, and combined imaging and therapy for cancer.
Department of Chemical Engineering and Materials Science, University of California, Irvine, California 92697, USA.
Min Suk
MS
Shim
Chang Soo
CS
Kim
Yeh-Chan
YC
Ahn
Zhongping
Z
Chen
Young Jik
YJ
Kwon
D000818:Animals; D001483:Base Sequence; D020868:Gene Silencing; D006046:Gold / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D053768:Metal Nanoparticles / Q000737:chemistry* / Q000627:therapeutic use; D051379:Mice; D008853:Microscopy; D057054:Molecular Imaging; D041681:NIH 3T3 Cells; D009369:Neoplasms / Q000175:diagnosis / Q000628:therapy; D055620:Optical Phenomena; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D011094:Polyethyleneimine / Q000737:chemistry; D034741:RNA, Small Interfering / Q000737:chemistry* / Q000235:genetics*; D013056:Spectrophotometry, Ultraviolet; D013499:Surface Properties
D034741:RNA, Small Interfering; D011092:Polyethylene Glycols; D006046:Gold; D011094:Polyethyleneimine