Delivery vehicles
Lipid-based nanoparticles
Delivery vehicles need to protect, transport and deliver their cargo while having to bypass various barriers they encounter from administration to entry into the cell. Despite the clinical success of lipid nanoparticles (LNPs), as seen during the COVID-19 pandemic, and other lipid carriers such as vesicles, there remain significant barriers to their applications and rational design such as the ability to control size, shape, stability and their inherent structural heterogeneity limiting insight into their structure–function relationships. Another key limitation is their limited endosomal escape, with clinical formulations leading to protein expression of only a couple of percent.
We engineer a variety of lipid-based nanoparticles (LNPs, vesicles, lyotropic liquid crystalline, as well as hybrid lipid-polymer) to address their current limitations, make them stimuli-responsive, targeted to specific disease sites, as well as understand the impact of formulation and their interaction with biologically relevant components. We aim to correlate their structure to their function and to enable more efficient and safer intracellular delivery of cargo for vaccines and other advanced treatments such as gene editing.
Key references:
Xu Z., Seddon J.M., Beales P.A., et al; Breaking Isolation to Form New Networks: pH-Triggered Changes in Connectivity inside Lipid Nanoparticles. J Am Chem Soc 143, (40), 16556-16565 (2021).
Pramanik A., Xu Z., Shamsuddin S.H., et al; Affimer Tagged Cubosomes: Targeting of Carcinoembryonic Antigen Expressing Colorectal Cancer Cells Using In Vitro and In Vivo Models. ACS Appl Mater Interfaces 14, (9), 11078-11091 (2022).
Xu Z., Booth A., Rappolt M., et al; Topological and Morphological Membrane Dynamics in Giant Lipid Vesicles Driven by Monoolein Cubosomes. Angew Chem Int Ed Engl, 64, (5), e202414970 (2025).
Microbubbles
Many solid tumours and bacterial biofilms possess physical and chemical barriers that hinder drug delivery. For example, many solid tumours have increased tissue stiffness, high interstitial pressure, and reduced interstitial flow, which is a critical barrier for drug delivery. Microbubbles can enhance drug delivery and by increasing cell membrane permeability through sonoporation, restoring interstitial flow and improving therapeutic efficacy.
We develop microbubbles (small gas filled bubbles), to directly deliver a variety of cargo to diseased sites such as tumours, biofilms, as well as for oxygen delivery with applications in cancer treatment, antimicrobial resistance and gene therapy. The microbubbles also act as imaging agents with enhanced sensitivity and specificity.
Key references:
Leeds Microbubble Consortium website
Batchelor D.V.B., Lad A., Burr K.L., et al. S. aureus biofilm disruption using ultrasound and microbubbles: Influence of radiation force, bubble dynamics and biofilm growth conditions. Biofilm 10, 100327 (2025).
Kpeglo D., Haddrick M., Knowles M.A., et al.; Modelling and breaking down the biophysical barriers to drug delivery in pancreatic cancer. Lab Chip 24, (4), 854-868 (2024).
Ingram N., McVeigh L.E., Abou-Saleh R.H., et al.; Ultrasound-triggered therapeutic microbubbles enhance the efficacy of cytotoxic drugs by increasing circulation and tumor drug accumulation and limiting bioavailability and toxicity in normal tissues. Theranostics 10, (24), 10973-10992 (2020).