Developing Impermeable Nanocapsules for Efficient Remote Delivery of Cytotoxic Drugs at Precise Locations

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Cancer therapeutics have dramatic side effects on healthy tissues. A prominent research area focuses on encapsulating cytotoxic drugs for targeted delivery to cancer tissues thereby reducing off-target side-effects. However, significant challenges remain for encapsulated clinical drugs.1. Drug loading is low and the manufacturing process is inefficient and expensive2. Once encapsulated, drug leaching over time is often high (especially on dilution)3. Typically, release specifically within tumours is not achieved.Recently developed methods for metallic-shell microcapsules able to permanently retain small molecules and to burst release payloads via ultrasound-based remote activation have recently evolved to produce nanocapsules (50-120nm) that can permanently encapsulate a chemotherapeutic drug (Paclitaxel). This delivery method addresses the above challenges simultaneously by ensuring that a high drug content is present within the nanocapsule cores, that no leaching occurs prior to reaching the site of action, thus preventing any side-effects and that local release of the drugs can be achieved through the use of ultrasound.This project will further develop this methodology and address very important aspects of the technology, which are key for working towards uptake of this delivery method by industry.This project addresses key aspects of cytotoxic drug delivery in a different manner by focusing on developing nano-objects, which aim to prevent side-effects by stopping leaching of the drugs, which is a typical drawback of most current nano-objects (e.g. liposomes, vesicles, micelles, nanoparticles), particularly upon dilution in the bloodstream.Chemotherapy treatment efficacy is still restricted by our inability to deliver high enough doses to allow complete control of cancer cells, resulting from the need to limit systemic drug levels due to toxicity in non-target tissues. Nevertheless, current (low) systemic doses still induce dramatic patient life quality reduction with the majority of administered drugs causing side effects to the rest of the body rather than reaching tumours.Here, a new method for delivering highly toxic chemotherapy drugs at high doses only within the tumour vicinity is developed by locally/remotely releasing drugs encapsulated within metal-shell nanocapsules that prevent any drug leaching prior to activation.Responsible innovation in this project is based on two aspects: 1) understanding the potential toxicity of the metal nanocapsules on human cells in-vitro and on mouse models in-vivo and 2) considering the toxicity of 'potentially stray' nanocapsules on the environment.