Encapsulation of a Ru(II) Polypyridyl Complex into Polylactide Nanoparticles for Antimicrobial Photodynamic Therapy

Abstract

Antimicrobial photodynamic therapy (aPDT) also known as photodynamic inactivation (PDI) is a promising strategy to eradicate pathogenic microorganisms such as Gram-positive and Gram-negative bacteria. This therapy relies on the use of a molecule called photosensitizer capable of generating, from molecular oxygen, reactive oxygen species including singlet oxygen under light irradiation to induce bacteria inactivation. Ru(II) polypyridyl complexes can be considered as potential photosensitizers for aPDT/PDI. However, to allow efficient treatment, they must be able to penetrate bacteria. This can be promoted by using nanoparticles. In this work, ruthenium-polylactide (RuPLA) nanoconjugates with different tacticities and molecular weights were prepared from a Ru(II) polypyridyl complex, RuOH. Narrowly-dispersed nanoparticles with high ruthenium loadings (up to 53%) and an intensity-average diameter < 300 nm were obtained by nanoprecipitation, as characterized by dynamic light scattering (DLS). Their phototoxicity effect was evaluated on four bacterial strains (Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli and Pseudomonas aeruginosa) and compared to the parent compound RuOH. RuOH and the nanoparticles were found to be non-active towards Gram-negative bacterial strains. However, depending on the tacticity and molecular weight of the RuPLA nanoconjugates, differences in photobactericidal activity on Gram-positive bacterial strains have been evidenced whereas RuOH remained non active.

Amplify Antimicrobial Photo Dynamic Therapy Efficacy With Poly-beta-amino Esters (PBAEs)

“…The higher vulnerability of Gram+ over Gram-observed in this study (Figure 5) was expected in line with several studies [43][44][45] . The higher susceptibility of Gram+ bacteria to PDT is widely considered to be explained by the relatively porous layer of peptidoglycan and lipoteichoic acid constituting the cell wall that allows the photosensitiser to cross the cell wall compared to the cell envelope of Gram-bacteria that exhibit higher resistance to photosensitiser uptake 43 .…”

Photodynamic Therapy Review: Principles, Photosensitizers, Applications, and Future Directions

“…The organic fluorophores, such as naphthalimides, xanthenes, boron dipyrromethene (BODIPY), and cyanines, can also be designed as photosensitizers for cancer PDT, with high light absorption at relatively long wavelengths and large molar extinction coefficient. Organic fluorophore photosensitizers have low toxicity, good biocompatibility, and long triplet lifetimes, and their fluorescence emission can be used to perform real-time monitoring during PDT treatment [ 40 , 41 ].…”

Ruthenium‐based Photoactive Metalloantibiotics†

“…Polymeric nanoparticles have also been shown to increase the quantum yield of singlet oxygen by preventing quenching effects that some photosensitizers exhibit in water (98). Ruthenium(II) polypyridyl complex, [Ru(bpy) 2 (dppz‐7‐hydroxymethyl)][PF 6 ] 2 , (dppz = dipyrido[3,2‐a:2;2′,3′‐c]phenazine) (RuOH) was conjugated to the end chain of a lipophilic polylactide (PLA) to form Ru‐polylactide (Ru‐PLA) nanoconjugates with different molecular weight and tacticities (99). The Ru‐PLA nanoconjugates display enhanced luminescence and increased singlet oxygen quantum yield compared to the RuOH alone.…”