Journal
BIOMATERIALS SCIENCE
Volume 9, Issue 6, Pages 2295-2312Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/d0bm01970d
Keywords
-
Categories
Funding
- Ministry of Human Resource Development (MHRD), Government of India
- Indian Institute of Technology (IIT) Indore, India
- Newton-Bhabha Research Fellowship, Keele University
- British Council
Ask authors/readers for more resources
This report presents the development of a novel near-infrared nanoprobe PSMA-QD655 for intraoperative navigation in prostate cancer surgery, showing high affinity and penetrative capacity in vitro 2D and 3D tissue models.
The current challenge in fluorescence guided surgery (FGS) for prostate cancer (PCa) is in the design of imaging probes with high selectivity, clear visualization of tumour margins, and minimal toxicity. This report aims to design and develop a novel NIR-nanoprobe, and evaluate its potential in the penetration of PCa tumour tissues. The PSMA receptor-targeted quantum dot (PSMA-QD655) is a NIR, deep-tissue imaging agent, which has the potential for intraoperative navigation during surgery and improved detection specificity for PCa. The probe was designed and synthesized by conjugating functionalized amino-PEG quantum dots (QDs) through a heterobifunctional linker to a DUPA targeted polypeptide construct. The nanoprobe was evaluated in vitro in PSMA(+) PCa cell lines for specificity and its binding affinity was determined by flow cytometric analysis. The penetration efficacy was tested further on large PCa 3D tumour spheroids (dia similar to 1200 mu m, thickness similar to 450 mu m) by deep tissue multiphoton imaging. PSMA-QD655 was found to be an efficient deep tissue intra-operative guided surgical tool with a high affinity (K-D = 15.3 nM) and penetrative capacity. The results have been demonstrated in vitro in 2D and 3D tissue models, mimicking cancer lesions in vivo. In summary, we have developed a deep-tissue imaging NIR nanoprobe targeting prostatic lesions that (i) binds to PSMA(+) tumour with sub-nanomolar affinity and high specificity, (ii) shows an excellent safety profile in primary cell lines in vitro and (iii) shows high penetrative capacity in a 3D prostate tumour model (similar to 450 mu m tissue depth).
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available