Exploring Light-Sensitive Nanocarriers for Simultaneous Triggered Antibiotic Release and Disruption of Biofilms Upon Generation of Laser-Induced Vapor Nanobubbles

Abstract

Impaired penetration of antibiotics through bacterial biofilms is one of the reasons for failure of antimicrobial therapy. Hindered drug diffusion is caused on the one hand by interactions with the sticky biofilm matrix and on the other hand by the fact that bacterial cells are organized in densely packed clusters of cells. Binding interactions with the biofilm matrix can be avoided by encapsulating the antibiotics into nanocarriers, while interfering with the integrity of the dense cell clusters can enhance drug transport deep into the biofilm. Vapor nanobubbles (VNB), generated from laser irradiated nanoparticles, are a recently reported effective way to loosen up the biofilm structure in order to enhance drug transport and efficacy. In the present study, we explored if the disruptive force of VNB can be used simultaneously to interfere with the biofilm structure and trigger antibiotic release from light-responsive nanocarriers. The antibiotic tobramycin was incorporated in two types of light-responsive nanocarriers—liposomes functionalized with gold nanoparticles (Lip-AuNP) and graphene quantum dots (GQD)—and their efficacy was evaluated on Pseudomonas aeruginosa biofilms. Even though the anti-biofilm efficacy of tobramycin was improved by liposomal encapsulation, electrostatic functionalization with 70 nm AuNP unfortunately resulted in premature leakage of tobramycin in a matter of hours. Laser-irradiation consequently did not further improve P. aeruginosa biofilm eradication. Adsorption of tobramycin to GQD, on the other hand, did result in a stable formulation with high encapsulation efficiency, without burst release of tobramycin from the nanocarriers. However, even though laser-induced VNB formation from GQD resulted in biofilm disruption, an enhanced anti-biofilm effect was not achieved due to tobramycin not being efficiently released from GQD. Even though this study was unsuccessful in designing suitable nanocarriers for simultaneous biofilm disruption and light-triggered release of tobramycin, it provides insights into the difficulties and challenges that need to be considered for future developments in this regard.

Functionalized Chitosan Nanomaterials: A Jammer for Quorum Sensing

“…Several researchers are trying to use functionalized nanoparticles to resist biofilm formation, where gold particles (GNPs) functionalized with enzyme proteinase K were found to be effective against Pseudomonas fluorescens biofilms [19]; silica nanoparticles functionalized with either peppermint oil (P-Cap) alone or in combination with cinnamaldehyde (CP-Cap) were found to halt the complex biofilm formation of Pseudomonas aeruginosa, E. coli DH5, S. aureus, and Enterobacter cloacae [20]; and amine-, carboxylate-, and isocyanate-functionalized superparamagnetic-iron oxide nanoparticles (IONs) against S. aureus biofilms are noteworthy [21]. Gold-nanoparticle-functionalized liposomes containing tobramycin could decrease biofilm biomass by approximately 1.5 times as compared to untreated liposomes containing tobramycin only [22]. A catheter surface that was functionalized with MgF(2) nanoparticles (NPs) effectively removed the biofilm from it [23].…”

Nanoplatforms for Sepsis Management: Rapid Detection/Warning, Pathogen Elimination and Restoring Immune Homeostasis

“…Liposomes, the most representational lipid-based NPs, consist of biomembrane-like phospholipid bilayers that confer membrane affinity and allow favorable drug encapsulation for both hydrophilic and hydrophobic agents. Benefiting from these advantages, liposomes can overcome host biomembrane barriers or biofilms generated by multidrug-resistant strains, delivering antimicrobial agents directly to bacteria [ 196 , 197 ]. In addition, liposomes have been reported to successfully combat the outer membrane barrier of Gram-negative bacteria and deliver antibiotics into bacterial cells for significantly improved activity [ 198 ].…”

Nanomaterials for Treating Bacterial Biofilms on Implantable Medical Devices

“…In a later study, the authors used these laser-induced VNB to functionalize the nanocarriers containing antibiotics for P. aeruginosa biofilm treatment ( Figure 6 ). The AuNPs functionalized liposomes containing tobramycin reduced the CFU and biofilm biomass by approximately four times and 1.5 times as compared to untreated and liposomes containing tobramycin only, respectively [ 72 ].…”

“…Impaired biofilm diffusion is caused by the fact that sessile cells cluster together into dense aggregates of hundreds of micrometers in size and because of the multi-component nature of the biofilm matrix which can trap molecules in their passage through biofilms. The mechanical impact of laser-induced VNB could increase the space between sessile cells, leading to a better flux and the effectivity of antimicrobial agents and their mechanical force can trigger antibiotic release from nanocarriers close to sessile bacteria (reproduced from [ 72 ] with permission from MDPI, 2019).…”