Barbieri, Valentino; (2024) Hybrid Au/polymer vesicles as photoactive nanomedical agents. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Polymersomes, amphiphilic block-copolymer vesicles, are well-established nanocarriers with optimal characteristics for the targeted intracellular delivery of therapeutics. The integration of inorganic nanomaterials into their membrane can be used to generate hybrid systems with added functionality and stimuli- responsiveness. The incorporation of gold nanoparticles (AuNPs) is particularly promising for the development of new nanomedical therapeutic strategies that leverage their unique plasmonic properties. Among other preparation methods, the in situ synthesis of AuNPs within polymersome membranes guarantees superior preservation of the vesicle morphology, colloidal stability and bioefficacy. Yet, it is unclear whether AuNPs grown in situ can endow hybrid polymersomes with detectable thermoplasmonic properties. In this work, hybrid polymersomes including AuNPs of narrowly distributed sizes around 2 nm within the polymer membrane were successfully fabricated by the in situ synthesis. The Au loading capacity is fine-tuned at the reaction design stage, reaching over 250 AuNPs per polymersome without compromising the integrity and stability of the system, which are conserved for over a year. These hybrid polymersomes can exhibit a substantial thermoplasmonic response to laser excitation. Through collective heating, concentration-dependent temperature increments up to 12 K were measured in dilute suspensions. To rationalise experimental trends, a novel theoretical model describing the collective plasmonic heating of hybrid polymersomes in therapeutically relevant scenarios was developed. Finally, the applicability of hybrid polymersomes as nanomedical agents was demonstrated through the successful in vitro photothermal killing of glioblastoma cells. Thanks to specific polymer-receptor interactions, hybrid polymersomes are abundantly endocytosed by cancer cells. Based on experimental evidence gathered through various techniques, it is speculated that the localised collective plasmonic heat generated by AuNP-rich assemblies confined in endosomes induces photothermal cell death under laser stimulation. We envision that this nanotechnological platform can act as a launch pad for the future development of hybrid localised photothermal treatments.

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