1 research outputs found
A targeted near-infrared nanoprobe for deep-tissue penetration and imaging of prostate cancer
Fluorescent guided surgery (FGS) has been highlighted as a potential to increase precision of
diseased tissue whilst minimising the removal of surrounding healthy tissue, particularly
relevant for increasingly prevalent prostate cancer (PCa). There remain challenges in the
design of imaging probes presenting high selectivity for tumour tissue, clear visualization and
minimal toxicity. Here we report the design and development of a novel NIR-nanoprobe and
evaluate its potential in penetration inside PCa tumour tissues. Prostate-specific membrane
antigen (PSMA) receptor-targeted near infrared emitting quantum dots (PSMA-NIR-QDot)
are demonstrated as deep tissue imaging agents for intraoperative navigation during surgery
and improving detection specificity for PCa. Probes were designed and synthesized by
conjugating functionalized amino-PEG QDots through a heterobifunctional linker to a DUPA
targeted polypeptide construct. Nanoprobes were evaluated in vitro in PSMA+ PCa cell lines
for specificity and affinity determined by flow cytometric analysis. The penetration efficacy
was tested further on large PCa 3D tumour spheroids (dia ~ 1.2 mm, width ~ 250 µm) by
deep tissue multiphoton imaging. The PSMA-NIR-Qdot was found to be an efficient deep
tissue penetrating intra-operative guided surgical tool with high affinity (KD = 15 nM) and
penetrative capacity. The results have been demonstrated in vitro in 2D and 3D tissue models,
mimicking cancer lesions in vivo. The presented deep-tissue imaging NIR nanoprobes target
prostatic lesions that (i) bind to PSMA+
tumour with sub-nanomolar affinity and high
specificity, (ii) show excellent safety profile in primary cell lines in vitro, and (iii) show high
penetrative capacity in 3D prostate tumour model (~ 250 µm tissue depth). These probes may
potentially offer vastly improved surgical accuracy for diseased tissue removal.</p