Engineering Plasma-Polymerised Nanoparticles for Breast Cancer Therapy

Abstract

Breast cancer remains one of the most prevalent cancers worldwide and a leading cause of cancer-related mortality among women. Polymeric nanoparticles (NPs) have strong potential to improve therapeutic efficacy by overcoming biological barriers associated with free drug administration; however, clinical translation is often hindered by wet-chemical synthesis methods that rely on toxic solvents, multi-step conjugation reactions, and complex purification, limiting scalability and regulatory approval. Plasma polymerisation offers a dry, reagent-free alternative for producing plasma-polymerised nanoparticles (PPNs) with surface-embedded, long-lived radicals that enable single-step, solvent-free covalent conjugation of biomolecules. This dissertation advances plasma polymerisation as a scalable strategy for engineering PPNs as next-generation nanocarriers for breast cancer therapy. Systematic optimisation of particle size, surface chemistry, and biofunctionalisation enhanced performance across key stages of drug delivery. A one-pot conjugation strategy was developed to functionalise PPNs with anticancer drugs and fluorophores and validated through comprehensive physicochemical characterisation. Fluorescently labelled PPNs demonstrated efficient cellular uptake, while drug-conjugated PPNs showed enhanced cytotoxic efficacy in both in vitro and in vivo breast cancer models. Long-term storage conditions were also established to preserve particle integrity and radical stability. Overall, this work establishes PPNs as a robust, scalable, and sustainable nanoplatform capable of improving the therapeutic performance of conventional drugs while addressing key translational limitations of traditional nanoparticle synthesis. Beyond oncology, the modular PPN platform demonstrates broad applicability for covalent functionalisation with biomolecules for imaging, biosensing, regenerative medicine, and gene therapy.