Engineered Polydopamine Nanocarriers for Biomedical Applications

Despite significant advancements in the field of nanomedicine and the design of drug nanocarriers, several critical challenges persist. These include limited cargo delivery due to uncontrolled drug release, off-target toxicity, premature aggregation, and rapid clearance of nano-formulations. Among the nanomaterials explored, organic nanostructures such as polydopamine (PDA) nanoparticles have emerged as promising candidates to tackle these challenges, owing to their excellent biocompatibility, ease of manufacturing, and versatile functionalisation. This thesis explores the potential of PDA nanoparticles in three key areas of biomedical application: the design of next-generation antibacterial therapeutics, drug delivery systems, and theranostics, which combine therapeutic properties with diagnostic capabilities (Figure 1. 1). In Chapter 2, an antibacterial agent was developed by synthesising a composite of PDA and silver nanoparticles, which was then employed as a microwave-triggered agent. Exposure to pulsed low-power microwaves commonly used in medical applications (2.45 GHz) significantly enhanced the antibacterial activity of the PDA-silver nanocomposite. Mechanistic studies revealed that this enhancement was attributed to several factors, including the intrinsic generation of reactive oxygen species (ROS), increased release of antimicrobial silver ions from the composite, and the enhanced accumulation of the nanocomposite at the bacterial surface, driven by the strong adhesive properties of PDA. Subsequently, in Chapter 3, the response of PDA to another critical stimulus, ultrasound, was explored for controlled drug delivery. To produce ultrasound-sensitive nanostructures and improve drug-loading capacity, hollow-core PDA (hPDA) nanoparticles were synthesised. Although these hPDA nanoparticles did not show an improved drug-loading capacity for the potent chemotherapeutic agent SN-38, they demonstrated significantly enhanced ultrasound-mediated drug release compared to solid-core nanoparticles. As a result, cytotoxicity studies revealed a 20% increase in the efficacy of SN-38@hPDA nanocarriers in pancreatic ductal adenocarcinoma cell lines when exposed to ultrasound, compared to control samples without ultrasound.

Name dc:type.qualificationname

Doctor of Philosophy (PhD)

Level dc:type.qualificationlevel

Doctoral

Grantor dc:publisher.institution

University of Cambridge

Year dc:date.issued

2024

Author dc:creator

• Lingamgunta, Swetha

Advisor dc:contributor.advisor

• Fruk, Ljiljana

• PDA
• NP
• Polydopamine
• Nanoparticles
• Ultrasound
• Microwaves
• Bacteria
• Cancer
• Nanotechnology
• Biotechnology

Licence

• https://www.repository.cam.ac.uk/bitstreams/1c58442f-2b7b-428d-b39d-d65baaf19d25/download
• http://purl.org/NET/rdflicense/allrightsreserved

Language dc:language

eng

DOI dc:identifier.doi

https://doi.org/10.17863/CAM.121810

OAI identifier oai:identifier

oai:www.repository.cam.ac.uk:1810/390155