<p><a>Molecular imaging revolutionized the way researchers and
clinicians visualize and investigate complex biochemical phenomena, and it is
beneficial </a><a>for
disease diagnosis, drug design and therapy assessment</a>. 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. </p>
<p>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 <i>in situ</i> and <i>in vivo</i>, 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.</p>
<p>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 <i>in vivo</i>. Taken together, it is demonstrated that BTII-DUPA
SPN is a promising targeted probe for prostate cancer diagnosis by PA imaging. </p>
<p>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 <i>in vivo</i>. 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. </p>
| Identifer | oai:union.ndltd.org:purdue.edu/oai:figshare.com:article/12148590 |
| Date | 19 April 2020 |
| Creators | Jiayingzi Wu (8727825) |
| Source Sets | Purdue University |
| Detected Language | English |
| Type | Text, Thesis |
| Rights | CC BY 4.0 |
| Relation | https://figshare.com/articles/PHOTOACOUSTIC_IMAGING_IN_THE_NIR-II_WINDOW_USING_SEMICONDUCTING_POLYMERS/12148590 |
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