Controlled Release of Functional Guest Molecules Using pH-Responsive Smart Microcompartments

Abstract

Protocells are designed to show one or multiple features of the living cells, such as membrane gating, encapsulation of biochemical molecules, movement, sensitivity to the surroundings, etc. Protocells with micro-compartmentalized structure can be synthesized through the bottom-up approach by spontaneous self-assembly of nanoparticles, nanoconjugates, lipid and polyelectrolytes. Protocell research has gained numerous interests in recent decades as it provides a promising way to bridge the missing parts between living and non-living matter.

Polyoxometalate coacervate vesicles (PCVs) is a hybrid coacervate protocell formed via spontaneous self-assembly of polyoxometalate/polyelectrolyte semi-permeable membrane around the outer surface of coacervate micro-droplets. The membrane-bounded microcompartment that can encapsulate various biological and chemical materials and be able to maintain its structure under various conditions.

In this thesis, the feasibility of PCVs as a drug release carrier was investigated with the aim to advance the practical application of protocells. The fabrication condition and the stability of hybrid polyoxometalate vesicles under different pH were first investigated. PCVs were observed to undergo decomposition under basic condition, leading to the release of the encapsulated molecules to the surrounding environment. Due to its unique pH-responsive property, PCVs can be applied to guest molecules release, thus in drug release systems. Three pH-responsive drug release systems were designed and investigated under microscopic and macroscopic levels. In the microscopic system, PCVs with encapsulated enzyme and guest molecules, and hierarchical dsDNA/Protamine microcapsules with active PCVs attached on their membrane were designed and constructed. In the macroscopic system, the guest molecules release system was constructed based on hydrogels with entrapped active PCVs. The programmable release of the target molecules in the above systems was studied and compared.

Date of Award	30 Sept 2025
Original language	English
Awarding Institution	University of Bristol
Supervisor	Avinash J Patil (Supervisor)