Iron-gold Nano-delivery Approaches for Cancer Cell Targeting and T-cell Redirecting

Abstract

Cancer is one of the most significant global public health issues. Traditional cancer treatments involve chemotherapy, surgery, and radiotherapy. However, these treatments are quite invasive and have varying success rates and adverse effects. Thus, more innovative strategies are required to treat cancer.

Targeted drug delivery is among the most promising innovative strategies. Every tumour has overexpressed special receptors; hence, delivery of a specifically targeted drug to those receptors can induce tumour regression. Drug delivery to the tumour can be achieved using nanoparticles. However, bioavailability could still be poor even with targeted drug delivery and when administered directly into the bloodstream. The bioavailability of nanomaterials can be improved greatly when delivered using a T-cell engager nanoparticles-based carrier system.

The aim of this thesis is to develop a next generation nanoparticle (NPs) based on immunotherapy T-cell engager. The NP complex will activate and recruit immune cells to cancer site in order to facilitate their killing effect.

Several strategies have been proposed to develop nanoparticle antibody complexes that have capability of targeting and killing cancer. These strategies are vital in the successful development of new generation immunotherapies and improving T-cell activation.

We developed a novel bispecific platform using a hybrid nanoparticle system. We thoroughly characterised our bispecifics and evaluated their cytotoxic capacity. Based on cytotoxic tests, our bispecifics are excellent drug candidates for various types of cancer.

This idea paves the way to target two mechanisms. The mechanisms include recognising and targeting cancer cells and activating T-cells to induce an immune response involving T-cell proliferation and cytokine production, which leads to the elimination of cancer cells. These concepts are further discussed in subsequent chapters of this thesis.