<p>Targeted Nanobubbles Carrying Indocyanine Green for Ultrasound, Photoacoustic and Fluorescence Imaging of Prostate Cancer</p>

Abstract

Objective: To construct prostate-specific membrane antigen (PSMA)-targeting, indocyanine green (ICG)-loaded nanobubbles (NBs) for multimodal (ultrasound, photoacoustic and fluorescence) imaging of prostate cancer. Methods: The mechanical oscillation method was used to prepare ICG-loaded photoacoustic NBs (ICG NBs). Then, PSMA-binding peptides were connected to the surface of ICG NBs using the biotin-avidin method to make targeted photoacoustic NBs, namely, PSMAP/ICG NBs. Their particle sizes, zeta potentials, and in vitro ultrasound, photoacoustic and fluorescence imaging were examined. Confocal laser scanning microscopy and flow cytometry were used to detect the binding ability of the PSMAP/ICG NBs to PSMA-positive LNCaP cells, C4-2 cells, and PSMAnegative PC-3 cells. The multimodal imaging effects of PSMAP/ICG NBs and ICG NBs were compared in nude mouse tumor xenografts. Results: The particle size of the PSMAP/ICG NBs was approximately 457.7 nm, and the zeta potential was approximately −23.5 mV. Both confocal laser scanning microscopy and flow cytometry confirmed that the PSMAP/ICG NBs could specifically bind to both LNCaP and C4-2 cells, but they rarely bound to PC-3 cells. The ultrasound, photoacoustic and fluorescence imaging intensities of the PSMAP/ICG NBs in vitro positively correlated with their concentrations. The ultrasound and photoacoustic imaging effects of the PSMAP/ICG NBs in LNCaP and C4-2 tumor xenografts were significantly enhanced compared with those in PC-3 tumor xenografts, which were characterized by a significantly increased duration of ultrasound enhancement and heightened photoacoustic signal intensity (P < 0.05). Fluorescence imaging showed that PSMAP/ICG NBs could accumulate in LNCaP and C4-2 tumor xenografts for a relatively long period. Conclusion: The targeted photoacoustic nanobubbles prepared in this study can specifically bind to PSMA-positive prostate cancer cells and have the ability to enhance ultrasound, photoacoustic and fluorescence imaging of PSMA-positive tumor xenografts. Photoacoustic imaging could visually display the intensity of the red photoacoustic signal in the tumor region, providing a more intuitive imaging modality for targeted molecular imaging. This study presents a potential multimodal contrast agent for the accurate diagnosis and assessment of prostate cancer.

Photoacoustic Properties of Polypyrrole Nanoparticles

“…We also confirmed that polypyrrole nanoparticles provided a substantially higher PA signal at the same experimental conditions than a commercial ICG, which is broadly used as a photoacoustic tracer or label [ 43 , 44 , 45 ]. The intent of the study was indeed the physical characterization of the particles, which may enable further optimization of their preparation for future applications.…”

Targeted contrast agents and activatable probes for photoacoustic imaging of cancer

“…Since recognizing its link to cancer, PSMA has emerged as an attractive target for the development of diagnostic tools via PA imaging. 157–160…”

“…13a). 158 To achieve this, authors loaded phospholipid-based bubbles with ICG and appended PSMA-binding peptide (WQPDTAHHWATL) via a biotin–streptavidin linkage. After obtaining promising in vitro results, they sought to investigate the PA enhancement of their nanobubbles, PSMAP/ICG NBs, in vivo .…”

Broad-Spectrum Theranostics and Biomedical Application of Functionalized Nanomaterials

“…This nanoparticle effectively bound to PSMA-positive prostate cancer cells, LNCaP cellsand C4-2 cells, and also enhancedthe imaging potential of multimodal techniques. Ultimately, this multimodal contrast agent was found to helpwith prostate cancer diagnosis and assessment [ 169 ]. A study designed the USF contrast agents (ICG-NPs and ExiTron nano 12000) with particle sizes ranging from 70 nm to 330 nm and administered themintravenously to understand the distribution of contrast agents in tumor and normal tissues including liver, kidney, and spleen.…”