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Enhanced NIR-II Nanoparticle Probe for PSMA-Targeted Molecular Imaging and Prostate Cancer Diagnosis

Year: 2025

Type: article

Abstract: Introduction: Prostate-specific membrane antigen (PSMA) is a well-established biomarker overexpressed in prostate cancer (PCa). However, existing PSMA-targeted imaging probes suffer from radiation exposure, limited tissue penetration, and inadequate intraoperative performance. To overcome these challenges, we developed a novel near-infrared-II (NIR-II) fluorescent nanoprobe for both in vivo and ex vivo imaging of PCa. Methods: An organic semiconducting polymer (OSP 12 ) with strong NIR-II fluorescence and excellent photostability was self-assembled into nanoparticles (NPs) using DSPE-PEG-Mal. These OSP 12 NPs were then conjugated with ACUPA-SH, (S)-2-[3-((S)-5-amino-1-carboxypentyl)ureido]pentanedioic acid, a thiol-modified glutamate-urea-lysine derivative that specifically targets PSMA, via a maleimide-thiol click reaction to form PSMA-OSP 12 NPs. The probe’s targeting specificity was assessed using PSMA positive and negative cell lines under NIR-II imaging. For in vivo evaluation, subcutaneous xenograft tumors were established in BALB/c nude mice. Animals were randomly assigned to PSMA-OSP 12 NP, blocking (ACUPA pre-injection), and control (OSP 12 NPs) groups (n = 3 per group). Ex vivo tumor slice imaging was performed on fresh tissue sections. Biosafety was evaluated in healthy mice (n=5) through hematological, biochemical, and histopathological analyses. Results: PSMA-OSP 12 NPs exhibited excellent optical properties in the NIR-II window, including high photostability, negligible autofluorescence, and deep tissue penetration. In vitro assays confirmed selective binding to PSMA-positive cells, while in vivo imaging demonstrated sustained tumor accumulation with a peak TBR of 7.40 ± 1.28 at 48 h post-injection. This performance significantly surpassed OTL78 and Cy-KUE-OA, enabling flexible surgical planning and real-time intraoperative guidance. In ex vivo tissue imaging, PSMA-OSP 12 NPs provided high-contrast tumor delineation without systemic administration. Biosafety evaluations revealed no significant systemic toxicity, and biodistribution analysis indicated hepatic metabolism and biliary clearance. Conclusion: PSMA-OSP 12 NPs are a promising NIR-II fluorescent probe with excellent tumor specificity, deep tissue imaging capability, and good biocompatibility, supporting their application in fluorescence-guided surgery and ex vivo tumor evaluation. Keywords: prostate cancer, prostate-specific membrane antigen, NIR-II, fluorescence-guided surgery, tumor targeting, molecular imaging, organic semiconducting polymer, nanoparticles

Source: International Journal of Nanomedicine

DOI: 10.2147/ijn.s532080