Optical Fibre-Enabled Photoswitching for Localised Activation of an Anti-Cancer Therapeutic Drug

Abstract

Local activation of an anti-cancer drug when and where needed can improve selectivity and reduce undesirable side effects. Photoswitchable drugs can be selectively switched between active and inactive states by illumination with light; however, the clinical development of these drugs has been restricted by the difficulty in delivering light deep into tissue where needed. Optical fibres have great potential for light delivery in vivo, but their use in facilitating photoswitching in anti-cancer compounds has not yet been explored. In this paper, a photoswitchable chemotherapeutic is switched using an optical fibre, and the cytotoxicity of each state is measured against HCT-116 colorectal cancer cells. The performance of optical-fibre-enabled photoswitching is characterised through its dose response. The UV–Vis spectra confirm light delivered by an optical fibre effectively enables photoswitching. The activated drug is shown to be twice as effective as the inactive drug in causing cancer cell death, characterised using an MTT assay and fluorescent microscopy. This is the first study in which a photoswitchable anti-cancer compound is switched using an optical fibre and demonstrates the feasibility of using optical fibres to activate photoswitchable drugs for potential future clinical applications.

Recent clinical trials and optical control as a potential strategy to develop microtubule-targeting drugs in colorectal cancer management

“…Although it is not related to combretastatins, endoscope-assisted phototherapy was carried out using a photoswitchable proteasome inhibitor and HCT-116 human CRC cell line recently[ 69 ]. Thus, photopharmacology was achieved with a CRC cell line model system.…”

Using GPCRs as Molecular Beacons to Target Ovarian Cancer with Nanomedicines

“…Additionally, recent design efforts have been directed toward the development of NP systems that feature stimuli-responsive drug release; triggered by light, redox reactions, temperature, or pH; further enhancing spatial or temporal drug release [64][65][66][67][68]. pHresponsivity is particularly advantageous in the context of cancer treatment, as the tumor milieu exhibits a characteristically lower pH (6.5-7.2) than physiological pH (7.4) due to lactic acid production [69].…”

Exploring Photoswitchable Binding Interactions with Small‐Molecule‐ and Peptide‐Based Inhibitors of Trypsin

“…[5,6] Such photoswitchable drugs have been reported to target ion channels, [7] receptors, [8] and enzymes, [9] for treatment of diseases such as cancers [10,11] and bacterial infections. [12] Despite reports of numerous such photoswitchable drugs, [6,13] and also novel ways to deliver the required light source where and when required, [13,14] most reported exam-ples only show a modest two-to tenfold difference in biological activity between isomers. [6] More recent studies have reported compounds with a > 20-fold difference, [15] however still only a few reported photoswitchable drugs have been trialled in animal studies [13] and there are even fewer examples of human clinical trials.…”