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Combined multimodal optical imaging and targeted gene silencing using stimuli-transforming nanotheragnostics.

ABSTRACT: 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.

SUBMITTER: Shim MS

PROVIDER: S-EPMC2903751 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature

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Combined multimodal optical imaging and targeted gene silencing using stimuli-transforming nanotheragnostics.

Shim Min Suk MS Kim Chang Soo CS Ahn Yeh-Chan YC Chen Zhongping Z Kwon Young Jik YJ

Journal of the American Chemical Society 20100601 24

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 ...[more]

PMID: 20518502

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Project description:Spatial frequency domain imaging (SFDI) applies patterned near-infrared illumination to quantify the optical properties of subsurface tissue. The periocular region is unique due to its complex ocular adnexal anatomy. Although SFDI has been successfully applied to relatively flat in vivo tissues, regions that have significant height variations and curvature may result in optical property inaccuracies. We characterize the geometric impact of the periocular region on SFDI imaging reliability. SFDI was employed to measure the reduced scattering coefficient ( μs' ) and absorption coefficient ( μa ) of the periocular region in a cast facial tissue-simulating phantom by capturing images along regions of interest (ROIs): inferior temporal quadrant (ITQ), inferior nasal quadrant (INQ), superior temporal quadrant (STQ), central eyelid margin (CEM), rostral lateral nasal bridge (RLNB), and forehead (FH). The phantom was placed on a chin rest and imaged nine times from an "en face" or "side profile" position, and the flat back of the phantom was measured 15 times. The measured μa and μs' of a cast facial phantom are accurate when comparing the ITQ, INQ, STQ, and FH to its flat posterior surface. Paired t tests of ITQ, INQ, STQ, and FH μa and μs' concluded that there is not enough evidence to suggest that imaging orientation impacted the measurement accuracy. Regions of extreme topographical variation, i.e., CEM and RLNB, did exhibit differences in measured optical properties. We are the first to evaluate the geometric implications of wide-field imaging along the periocular region using a solid tissue-simulating facial phantom. Results suggest that the ITQ, INQ, STQ, and FH of a generalized face have minimal impact on the SFDI measurement accuracy. Areas with heightened topographic variation exhibit measurement variability. Device and facial positioning do not appear to bias measurements. These findings confirm the need to carefully select ROIs when measuring optical properties along the periocular region.

Dataset Information

Combined multimodal optical imaging and targeted gene silencing using stimuli-transforming nanotheragnostics.

Publications

Combined multimodal optical imaging and targeted gene silencing using stimuli-transforming nanotheragnostics.

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