Surface Engineering of Protocells for Cascade Reactions and Drug Delivery

Abstract

Protocells that can mimic cellular behaviours provide a valuable opportunity for exploring synthetic biology and the origins of life. By engineering protocells with simple techniques, it is possible to introduce diverse functionalities and dynamic behaviours into these systems, offering potential applications in bioengineering and biomedical research.
In the first section, we demonstrate the surface engineering of inorganic protocells (colloidosomes) using a multilayer coating strategy that combines biopolymers and enzymes to create a programmable enzyme cascade reactor. The enzyme cascade reaction can beregulated by altering the enzyme coating sequence. Additionally, small molecules (substrates and products) can diffuse through the hybrid semipermeable membranes. As a result, these colloidal entities act as biocatalytic microreactors that mimic basic chemical signal
transduction processes observed in biological cells.
In the second section, we introduce a positive polymer coating on proteinosomes, which induces the movement of negatively charged payloads toward the membrane, triggering a shape change in the proteinosomes. Electrostatic interactions, hydrophobic interactions, and osmotic pressure changes play crucial roles in the coating, payload redistribution, and shape
transformation processes. The positively charged polymer-coated proteinosome membrane functions as a catalytic platform for negative enzymes and substrates by screening electrostatic repulsion between negatively charged substrates. The crumpled shape can be restored via a coacervation process, where the introduced negative molecules form coacervates with the
excess positive coating polymers, which then adhere to the proteinosome membrane, forming satellite-like composites.
In the third section, we use the satellite-like coacervate/proteinosomes composite model as a drug delivery platform. These composites combine the advantages of both coacervates and proteinosomes, offering stability, high drug-loading efficiency, and controlled drug release properties. pH-responsive PLL/AMP coacervate/proteinosome composites are utilized for
glucose-responsive release by encapsulating Glucose Oxidase inside the proteinosomes. Temperature-responsive protamine/citrate coacervate/proteinosome composites are employed
for the delivery of ibuprofen in fever treatment.

Date of Award	17 Jun 2025
Original language	English
Awarding Institution	University of Bristol
Supervisor	Stephen Mann (Supervisor) & B D A Naafs (Supervisor)