Photothermal nanoparticles for the control of infectious biofilms

Antimicrobial-resistant infections are becoming an increasingly serious health care problem and threaten to be the main cause of death by the year 2050. In Chapter 1, the current situation and expert opinions in infection control are summarized. Based on the current situation, it suggests that the alternative, non-antibiotic based pathways to eradicate bacterial infection should be taken. Therefore, in Chapter 2, we synthesized polydopamine, photothermal nanoparticles (PDA-NPs) without further surface-functionalization to evaluate their potential with respect to biofilm-control. Clinical application of photothermal nanoparticles initially involved tumor treatment. Application towards much smaller, micrometer-sized bacterial infections however, bears the risk of collateral damage by heat dissipating into tissue surrounding an infection site. In Chapter 3, we addressed the hitherto neglected potential complication of collateral tissue damage by evaluating photothermal, PDA-NP-coatings on titanium surfaces in different co-culture models. The lack of bacterial killing efficacy of photothermal nanoparticles towards an existing biofilm (Chapter 2) combined with the potential of collateral heat damage to surrounding tissue (Chapter 3), suggests that eradication of existing infectious biofilms requires modification of the nanoparticles to allow their penetration and accumulation in a biofilm. To this end, in Chapter 4, we encapsulated photothermal PDA-NPs in pH-responsive, mixed shell polymeric micelles, composed of stealth poly-ethylene glycol (PEG) and pH-sensitive poly (β-amino ester) (PAE). In Chapter 5, the advantages and disadvantages of photothermal nanoparticles as a non-antibiotic based infection-control strategy are discussed in depth in view of the findings presented in this thesis.