Towards Hybrid MRI Contrast Agent / Metal-based Drug Carrier with Minimal Adverse Effects

Early detection of cancer allows possibility of curative surgical resection/ chemotherapy/ chemoembolization thereby improving overall prognosis. Limitation of magnetic resonance imaging (MRI) in the detection of cancerous lesion can be overcome by the use of contrast agent. Self-assembling protein nanocapsule (PNC) has been shown as either a potential drug carrier or magnetic resonance imaging (MRI) contrast agent. One aspect of the PNC that is relatively unexplored is its potential as a multifunctional delivery system that allows both diagnosis and therapy of HCC. In this proposal, our goal is to develop multi-cargo PNC derived from Archaeglobus fulgidus (AfPNC) for therapeutic and diagnostic (theranostic) applications with minimal adverse effects. We hypothesize that the PNC cargo carrying ability is expandable beyond the formation of iron nanocore by concurrent loading of therapeutic agents. However, due to its non-human nature, the AfPNC may cause some unwanted responses in vivo. Minimization of the adverse effects is possible by functionalization of the external surface of the PNC. The specific aims of the project are:(1)Co-encapsulation optimization of iron (Fe) and metal-based small molecule drug (e.g. cis-platin (CDDP)) within the AfPNC through modulation of the AfPNC self-assembly property and assessment on the effect of the co-encapsulation on drug delivery/ image enhancement capabilities.(2)Improvement of the effectiveness, undesired side effects, shelf-life, and patient compliance by functionalization of the AfPNC external surface (e.g. poly-ethylene glycol (PEG)) and assessment on its half inhibitory concentration in vitro.(3)Investigation on cellular uptake in vitro and immunological properties of the AfPNC by testing for inflammatory response, circulatory half-life, and clearance rate as well as evaluation of contrast enhancement in vivo.Significance. The proposed work will provide an insight in the development of multifunctionalprotein-based delivery system which will allow advance diagnosis and therapy for HCC patients.