Near infrared fluorescence probes : towards applications in fluorescence guided surgery

Cheng, Hok Yan

Abstract

Surgery has been a popular method for the treatment of cancers, in particular solid tumours; but the surgical margins for cancerous tissues are often indistinct and in most cases, the poor identification of residual cancer tissues can result in re-excision. Therefore, near infrared (NIR) fluorescence-guided surgery (FGS) is being developed as a real time intra-operative imaging technique to assist surgeons by improving the accuracy and precision of the removal of tumours.

However, current FDA approved fluorophores suffer from poor chemical stability, limited water-solubility, and lack selectivity toward neoplastic tissue, limiting their clinical application. These current challenges have led to the development of new and improved fluorophores capable of absorbing and emitting light at NIR wavelengths, negating autofluorescence and improving deeper light transmission.

Throughout this project, a series of BODIPYs, aza-BODIPYs and bacteriochlorins were synthesised and developed for bioimaging applications. Despite many of them showing interesting fluorescence properties, the investigation suggested aza-BODIPYs were the most promising red / NIR fluorophores (λem 600-700 nm) due to their excellent photostability. Methods have been developed to incorporate functionalities suitable for bioconjugation.

Different bioconjugation strategies have been explored to covalently conjugate the NIR fluorophores to a clinically relevant protein, peptide and antibody under mild conditions. The viability of aza-BODIPY conjugates against biological targets were investigated and a range of other novel targeted NIR fluorophores were successfully developed. In vitro fluorescence imaging was subsequently carried out to demonstrate the enhanced selectivity of the targeting NIR fluorophores toward overexpressed receptors on various cancer cells lines.

This project has demonstrated the potential of aza-BODIPY in biological imaging and developed targeted NIR fluorophores. Further biological evaluation is progressing with the eventual aim of developing a pre-clinical model for NIR FGS in oncology.

Citation

Cheng, H. Y. (2017). Near infrared fluorescence probes : towards applications in fluorescence guided surgery. (Thesis). University of Hull. Retrieved from https://hull-repository.worktribe.com/output/4220740

• Thesis Type: Thesis
• Deposit Date: Oct 11, 2018
• Publicly Available Date: Feb 23, 2023
• Keywords: Chemistry
• Public URL: https://hull-repository.worktribe.com/output/4220740
• Additional Information: School of Mathematics and Physical Sciences, The University of Hull
• Award Date: Dec 1, 2017