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PHOTOACOUSTIC IMAGING IN THE NIR-II WINDOW USING SEMICONDUCTING POLYMERS

thesis
posted on 19.04.2020 by Jiayingzi Wu

Molecular imaging revolutionized the way researchers and clinicians visualize and investigate complex biochemical phenomena, and it is beneficial for disease diagnosis, drug design and therapy assessment. Among a variety of different imaging techniques, the non-ionizing and non-invasive photoacoustic (PA) imaging is attracting increased attentions, owing to its high spatial and temporal resolutions with reasonable penetration depth in tissue. Parallel efforts have been the preparation of PA imaging agents which has high PA efficacy and can specifically label the targets at cellular or molecular level. Particularly, there is exponentially growing interest in imaging in the second near-infrared (NIR-II) window (1000–1700 nm), where offers reduced tissue background and improved penetration depth. However, study of PA imaging in the NIR-II window is incomplete, partly due to the lack of suitable materials. Therefore, in my dissertation work I studied NIR-II PA imaging through semiconducting polymer.

Firstly, the performance of PA imaging in the NIR-II window is explored by using a semiconducting polymer nanoparticle (SPN) which has strong absorption in the NIR-II window. Compared with lipid, blood and water, such SPN shows outstanding PA contrast in the NIR-II window in situ and in vivo, and an imaging depth of more than 5 cm at 1064 nm excitation is achieved in chicken-breast tissue. These results suggest that SPN as a PA contrast in the NIR-II window opens new opportunities for biomedical imaging with improved imaging contrast and centimeter-deep imaging depth.

Next, targeted PA imaging of prostate cancer is achieved by functionalizing a NIR-II absorbing SPN with prostate-specific membrane antigen (PSMA)-targeted ligands. Insights into the interaction of the imaging probes with the biological targets are obtained from single-cell to whole-organ by transient absorption (TA) microscopy and PA imaging. TA microscopy reveals the targeting efficiency, kinetics, and specificity of the functionalized SPN to PSMA-positive prostate cancer at cellular level. Meanwhile, the functionalized SPN demonstrates selective accumulation and retention in the PSMA-positive tumor after intravenous administration in vivo. Taken together, it is demonstrated that BTII-DUPA SPN is a promising targeted probe for prostate cancer diagnosis by PA imaging.

Lastly, PA imaging in the NIR-II window is also achieved water-soluble semiconducting polymer, which is prepared by oxygen-doping. After doping, it shows broadband absorption in the entire NIR-II window, with great chemical stability, photostability and biocompatibility. Owing to its merit of broadband absorption, the imaging depth comparison among different NIR-II wavelengths is also achieved. Moreover, this doped semiconducting polymer is readily soluble in normal physiological pH by virtue of carboxyl groups on side chains and tends to aggregate at an acidic environment which results in a 7.6-fold PA enhancement at pH 5.0. Importantly, a 3.4±1.0-fold greater signal in tumor tissue than that in muscle is revealed in vivo. This study provides a more attainable yet effective platform to the field for achieving water-soluble NIR-II absorbing contrast agents for activatable PA imaging.

Funding

Keck Foundation

R01HL12385

Showalter Trust Research Award

History

Degree Type

Doctor of Philosophy

Department

Chemistry

Campus location

West Lafayette

Advisor/Supervisor/Committee Chair

Jianguo Mei

Additional Committee Member 2

Ji-Xin Cheng

Additional Committee Member 3

Chengde Mao

Additional Committee Member 4

Shelley Claridge

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