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.
Highlights
With an increasing number of microorganisms showing resistance to antibiotics, we are stepping into the “post-antibiotic” era—as World Health Organization (WHO) first reported in 2014—in which common and minor infections can be fatal [1]
Polymers derived from d,l-lactide yielded an amorphous polymer as a result of the random sequence of d and l-units along the polymer backbone, whereas polymers derived from the enantiopure monomers yielded semi-crystalline isotactic polymers PLLA and PDLA with a melting temperature Tm around 140 ◦C
Mixing two isotactic polylactides of opposite configurations (PLLA and PDLA) at an equimolar ratio allowed the formation of a stereocomplex characterized by superior physical properties, in particular thermal properties, with a Tm 60 ◦C higher than that of the respective homochiral polymers, in accordance with what has already been reported in the literature [37,38,39]
Summary
With an increasing number of microorganisms showing resistance to antibiotics, we are stepping into the “post-antibiotic” era—as World Health Organization (WHO) first reported in 2014—in which common and minor infections can (once again) be fatal [1] This major health concern has led to the development of new antimicrobial treatments, including antimicrobial photodynamic therapy (aPDT) [2,3,4]. The PS is promoted to an excited state from which it can interact with its biological surroundings to form reactive oxygen species (ROS), including the highly cytotoxic singlet oxygen (1O2) This technique was first introduced in 1900 by Oscar Raab when he reported the toxicity of acridine upon sunlight exposure towards Paramecia, a type of microorganism [5]. The growing interest in aPDT mainly relies on its multi-target nature involving the rapid and effective action of ROS, which makes it less prone to resistance, unlike conventional antimicrobial treatments [6]
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