LIght activatable Single component NAnosystems: proof of concept on bacterial biofilms – LISiNA
Many nanocarriers such as liposomes, organic and inorganic nanoparticles have been developed as drug delivery systems (DDS). Among myriads of successful applications, multifunctional/stimuli-responsive nanocarriers have emerged as a promising nanotechnology compared to conventional nanomedicines, due to their unique spatio-temporal controlled activation/release mechanism. However, the conception of these DDS presents several shortcomings, including the requirement for multistep synthesis and purification, complex toxicity studies for the multiple components necessary for providing the multifunctional properties, and potentially heterogeneous formulations that jeopardize clinical translation and production at industrial scale. The main objective of this proposal is to develop a new light-activatable DDS composed of a single multifunctional building block which can be used for the treatment of local bacterial infections without antibiotics. The proposed DDS allows bimodal therapy, Photothermal therapy (PTT)/Photodynamic therapy (PDT). Whereas, PTT consists on the conversion of adsorbed light energy by strong optical absorbent materials into cytotoxic heat, the PDT is based by reactive oxygen species (ROS) produced through either electron transfer (type I) or energy transfer reaction (type II) after interaction of a photosensitizer (PS) and light in the presence of dioxygen. The antibacterial efficacy of the DDS will be assessed on bacterial cultures and biofilms as a proof of concept. Biofilms are a complex organization of single or multi-bacterial species embedded in a protective extracellular polymeric matrix that presents high adherence on living or inert surfaces and interfaces. Owing to these properties, virulent biofilms can cause multiple persistent bacterial infections, such as subcutaneaous abcess, periodontitis, endocarditis, urethritis, otitis, chronic lung infections. Moreover, the biofilm mode of growth renders bacteria less susceptible to conventional antibacterial treatment. Indeed, bacteria inside a biofilm are up to 1000-fold more resistant than their planktonic counterparts towards antibiotics. Although, broad-spectrum antibiotics remain the first-line treatment for bacterial biofilms, however the non-prudent use of antibiotics has provoked an exponential increase in the incidence of the antibiotic resistance in several bacterial strains in recent years. As a consequence, biofilm-based infections can rarely be resolved.
Monsieur Ali Makky (Institut Galien Paris Sud)
The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.
IGPS Institut Galien Paris Sud
I2BC Institut de Biologie Intégrative de la Cellule
Help of the ANR 263,829 euros
Beginning and duration of the scientific project: December 2019 - 48 Months