Combined multi-target molecular ultrasono-graphy and photothermal therapy using cancer targeting gold nano rod probes

Dar-Bin Shieh, Ding An An, Ya Na Wu, Ying Yi Chen, Ren Chris Churng-Wang, Pai Chi Li

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

Ultrasound imaging is a relatively low cost, portable and non-invasive medical imaging modality for the diagnosis of a wide spectrum of diseases. Molecular imaging of diseases provide valuable information for improved disease diagnosis and management and has been developed to integrate into various medical imaging platform. However, no molecular probes has been developed for ultrasound imaging to date. In this study, we synthesized gold nano rod (AuNRs) with controllable aspect ratio as the core of molecular probe. The AuNR was modified with poly-ethylene glycol (PEG) and monocolonal antibody specific for the target biomolecules such as Her-2, CXCR4, EGFR in this research. The molecular photoacoustic ultrasonography. The AuNR probe exhibit surface plasmonic resonance frequency (SPR) proportional to their aspect ratio. Two type of AuNR with SPR at 785nm and 1000nm, respectively, were synthesized. The SPR spectra fall into NIR range of biological optical window and thus enabled better tissue penetration of the laser light. Interaction of AuNRs with laser irradiation was able to generate acoustic wave for image reconstruction and precision dynamic measurement of local fluid flow. In vitro study demonstrated a significant photoacoustic molecular imaging of Her-2 in the wild type cancer cells compared to the gene knock down cells mediated by stable transfection of RNAi. The use of molecular probes with different peak SPR frequencies enabled a differential molecular diagnosis of expression level of EGFR or Her2 oncogenes in two cell line models by modulation of laser wavelength. Molecular imaging of cancer bearing animals also obtained primary success with an augmentation in signal intensity from 3db to 5db by using multiple cocktail molecular probes. In addition, AuNR was found to absorb laser light with corresponding SPR frequency to generate local heat at nanometer scale range, which could be applied for precision hyperthermia therapy. AuNRs conjugated HER-2 antibodies successfully target tumor cells of high expression level and induced cancer cell death upon laser irradiation while spare the control cell line of low expression level. A laser wave length guided selective targeting cancer cell therapy was demonstrated using two types of molecular probes (anti-EGFR and anti-Her2) with different peak SPR and four different cancer cell lines. Combined cocktail probes targeting to the same cancer cell significantly improve therapeutic efficacy. In conclusion, a novel AuNR-molecular probe system that combined the power of photoacoustic molecular imaging and targeting therapy in one was developed and demonstrated to be effective. Future preclinical and clinical evaluation is warranted.

Original languageEnglish
Title of host publication2008 8th IEEE Conference on Nanotechnology, IEEE-NANO
Pages841-842
Number of pages2
DOIs
Publication statusPublished - 2008
Event2008 8th IEEE Conference on Nanotechnology, IEEE-NANO - Arlington, TX, United States
Duration: 2008 Aug 182008 Aug 21

Other

Other2008 8th IEEE Conference on Nanotechnology, IEEE-NANO
CountryUnited States
CityArlington, TX
Period08-08-1808-08-21

Fingerprint

Gold
Molecular imaging
Cells
Photoacoustic effect
Lasers
Medical imaging
Laser beam effects
Antibodies
Aspect ratio
Bearings (structural)
Hyperthermia therapy
Ultrasonics
Ultrasonography
Imaging techniques
Wavelength
Biomolecules
Cell death
Image reconstruction
Polyethylene glycols
Flow of fluids

All Science Journal Classification (ASJC) codes

  • Electrical and Electronic Engineering

Cite this

Shieh, D-B., An An, D., Wu, Y. N., Chen, Y. Y., Churng-Wang, R. C., & Li, P. C. (2008). Combined multi-target molecular ultrasono-graphy and photothermal therapy using cancer targeting gold nano rod probes. In 2008 8th IEEE Conference on Nanotechnology, IEEE-NANO (pp. 841-842). [4617232] https://doi.org/10.1109/NANO.2008.250
Shieh, Dar-Bin ; An An, Ding ; Wu, Ya Na ; Chen, Ying Yi ; Churng-Wang, Ren Chris ; Li, Pai Chi. / Combined multi-target molecular ultrasono-graphy and photothermal therapy using cancer targeting gold nano rod probes. 2008 8th IEEE Conference on Nanotechnology, IEEE-NANO. 2008. pp. 841-842
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abstract = "Ultrasound imaging is a relatively low cost, portable and non-invasive medical imaging modality for the diagnosis of a wide spectrum of diseases. Molecular imaging of diseases provide valuable information for improved disease diagnosis and management and has been developed to integrate into various medical imaging platform. However, no molecular probes has been developed for ultrasound imaging to date. In this study, we synthesized gold nano rod (AuNRs) with controllable aspect ratio as the core of molecular probe. The AuNR was modified with poly-ethylene glycol (PEG) and monocolonal antibody specific for the target biomolecules such as Her-2, CXCR4, EGFR in this research. The molecular photoacoustic ultrasonography. The AuNR probe exhibit surface plasmonic resonance frequency (SPR) proportional to their aspect ratio. Two type of AuNR with SPR at 785nm and 1000nm, respectively, were synthesized. The SPR spectra fall into NIR range of biological optical window and thus enabled better tissue penetration of the laser light. Interaction of AuNRs with laser irradiation was able to generate acoustic wave for image reconstruction and precision dynamic measurement of local fluid flow. In vitro study demonstrated a significant photoacoustic molecular imaging of Her-2 in the wild type cancer cells compared to the gene knock down cells mediated by stable transfection of RNAi. The use of molecular probes with different peak SPR frequencies enabled a differential molecular diagnosis of expression level of EGFR or Her2 oncogenes in two cell line models by modulation of laser wavelength. Molecular imaging of cancer bearing animals also obtained primary success with an augmentation in signal intensity from 3db to 5db by using multiple cocktail molecular probes. In addition, AuNR was found to absorb laser light with corresponding SPR frequency to generate local heat at nanometer scale range, which could be applied for precision hyperthermia therapy. AuNRs conjugated HER-2 antibodies successfully target tumor cells of high expression level and induced cancer cell death upon laser irradiation while spare the control cell line of low expression level. A laser wave length guided selective targeting cancer cell therapy was demonstrated using two types of molecular probes (anti-EGFR and anti-Her2) with different peak SPR and four different cancer cell lines. Combined cocktail probes targeting to the same cancer cell significantly improve therapeutic efficacy. In conclusion, a novel AuNR-molecular probe system that combined the power of photoacoustic molecular imaging and targeting therapy in one was developed and demonstrated to be effective. Future preclinical and clinical evaluation is warranted.",
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Shieh, D-B, An An, D, Wu, YN, Chen, YY, Churng-Wang, RC & Li, PC 2008, Combined multi-target molecular ultrasono-graphy and photothermal therapy using cancer targeting gold nano rod probes. in 2008 8th IEEE Conference on Nanotechnology, IEEE-NANO., 4617232, pp. 841-842, 2008 8th IEEE Conference on Nanotechnology, IEEE-NANO, Arlington, TX, United States, 08-08-18. https://doi.org/10.1109/NANO.2008.250

Combined multi-target molecular ultrasono-graphy and photothermal therapy using cancer targeting gold nano rod probes. / Shieh, Dar-Bin; An An, Ding; Wu, Ya Na; Chen, Ying Yi; Churng-Wang, Ren Chris; Li, Pai Chi.

2008 8th IEEE Conference on Nanotechnology, IEEE-NANO. 2008. p. 841-842 4617232.

Research output: Chapter in Book/Report/Conference proceedingConference contribution

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Shieh D-B, An An D, Wu YN, Chen YY, Churng-Wang RC, Li PC. Combined multi-target molecular ultrasono-graphy and photothermal therapy using cancer targeting gold nano rod probes. In 2008 8th IEEE Conference on Nanotechnology, IEEE-NANO. 2008. p. 841-842. 4617232 https://doi.org/10.1109/NANO.2008.250