Postgraduate Seminar Presentation : Molecular Engineering of Conjugated Polymers for Biocompatible Organic Nanoparticles with Highly Efficient Photoacoustic and Photothermal Performance in Glioma Theranostics

Speaker Guo Bing (Supervisor: Prof Liu Bin)

Host

Date/Time 13 Oct - 13 Oct, 3.00PM

Venue E5-02-32 , Faculty of Engineering, National University of Singapore

Synopsis

Photoacoustic (PA) imaging is a state-of-the-art diagnostic tool, which is undergoing active translation from bench-to-bedside. However, the use of PA imaging to delineate deep glioma remains challenging due to strong light attenuation of the skull, severe background interference and lack of intrinsic contrast agents within tumors. Importantly, PA imaging contrasts can also serve as photothermal therapeutic agents to ablate tumors. Recently, conjugated polymer nanoparticles (CP NPs) have emerged as candidates of “all-in-one” theranostic nanoplatforms for PA and photothermal applications. So far, very limited molecular design guidelines have been developed for achieving CP NPs with highly efficient PA and photothermal performance.

Herein, we applied molecular engineering approach to design CPs with different electron acceptors (A) and a planar electron donor (D), and demonstrated how the planar structure and D-A strength affect their absorption from the first near-infrared (NIR-I) window to the second near-infrared (NIR-II) window, emission, extinction coefficient, PA and photothermal performance.

For the NIR-I CP NPs, we examined the photothermal and PA performance on subcutaneous glioma. The resultant CP NPs show excellent biocompatibility in vitro and in vivo, with strong PA signals and high photothermal conversion efficiencies. The obtained CP NPs show extremely low IC50 value (0.88 μg/mL) for U87 glioma cell ablation, and they also offer a very high signal to background ratio (47) in PA imaging of U87 tumor-bearing mice. These results are significantly better than other reported PA and photothermal reagents, which prove that CP NPs are promising for future personalized nanomedicine.

For the NIR-II CPs, we examined the PA performance on orthotopic glioma. It is demonstrated that the 1064 nm pulse laser excitation is far more effective than other wavelength excitation (e.g., 800, 900 and 1210 nm) to achieve ultra-low background interference, significantly weakened light attenuation and highly enhanced signal/background ratio for brain tumor PA imaging. Due to the exceptional performance of the CP NPs, the PA signal in the glioma at 24 h post-injection is 94-fold of the initial PA signal before NP injection. In addition, as the first successful example of NIR II PA probe based glioma imaging, a very high tumor single intensity to background (composed of brain skull and skin) intensity ratio of more than 59 is achieved for a deep tumor at 3.4 mm underneath the skull. This study thus not only provides an insight into the design of CP nanoparticle-based NIR II PA contrast agents, but also demonstrates the superiority of 1064 nm PA imaging for deep glioma diagnosis.

Biography