Colorectal cancer is among the most commonly diagnosed cancer and ranks as the third leading cause of cancer related mortality worldwide. Chemotherapy remains an important strategy for patients diagnosed with advanced stage colorectal cancer. Compared to normal cells, cancer cells have intrinsically higher levels of reactive oxygen species (ROS). Increased reactive oxygen species in cancer cells is crucial in the initiation and progression of cancer. However, excessive ROS production could be toxic and render cancer cells to be more vulnerable to damage by further oxidative stress induced by exogenous agents. Oxidative stress has been reported to induce cell apoptosis via a series of downstream pathways, such as endoplasmic reticulum (ER) stress and mitochondrial cascade. Therefore, manipulating ROS levels in cancer cells is a way to selectively kill cancer cells, and has been involved in the anti-cancer effects of several therapeutic agents including auranofin, disulfiram, and piperlongumine. Cisplatin-based therapy is one of the most important chemotherapy treatments for cancers. However, its efficacy is greatly limited by drug resistance and undesirable side effects. A majority of cancer patients eventually relapse and develop drug resistance despite initial response to cisplatin.
In recent years, there has been a great interest in the development of self-assembled discrete metallosupramolecular architectures such as cages and capsules. Remarkable advances have been made in tuning the ability of these self-assembled molecular cages and capsules to demonstrate host-guest chemistry towards widespread applications in sensing, catalysis and as small-molecule delivery systems. However, many existing systems lack the ability to self-assemble (or dis-assemble) in response to an external stimuli (for example light or pH) which limits the ability of these existing structures to exhibit more sophisticated functions for instance operating as drug delivery systems with targeted release mechanisms. Herein, we aim to develop molecular cages that display responsive behaviour that can be employed towards the encapsulation and controlled release of the anti-cancer drug, cis-platin. The development of these responsive molecular cages will lead to the creation of a new generation of anti-cancer drugs delivery systems with targeted release mechanisms which possess the potential to deliver anti-cancer drugs at the specific site of cancer within the body.
Furthermore, microfluidic reactors will be used to produce fabricate the system into nanoparticulate form to enhance its bioavailability. Nano forms of medicine are known to have a higher dissolution rate as well as higher level of cell penetration. Nano suspensions as well as liposomal forms will be investigated to identify the most suitable form of delivery.
This is a self-funded PhD project; applicants will be expected to pay their own fees or have a suitable source of third-party funding. A bench fee also applies in addition to tuition fees.