Poly Lactic-co-Glycolic Acid (PLGA) Loaded with a Squaraine Dye as Photosensitizer for Antimicrobial Photodynamic Therapy.

Antimicrobial Photodynamic Therapy (aPDT) is an innovative and promising method for combating infections, reducing the risk of antimicrobial resistance compared to traditional antibiotics. Squaraine (SQ) dyes can be considered promising photosensitizers (PSs) but are generally hydrophobic molecules that can self-aggregate under physiological conditions. To overcome these drawbacks, a possible solution is to incorporate SQs inside nanoparticles (NPs). The present work deals with the design and development of innovative nanophotosensitizers based on poly lactic-co-glycolic acid (PLGA) NPs incorporating a brominated squaraine (BrSQ) with potential application in aPDT. Two designs of experiments (DoEs) based on the single emulsion and nanoprecipitation methods were set up to investigate how different variables (type of solvent, solvent ratio, concentration of PLGA, stabilizer and dye, sonication power and time) can affect the size, zeta (ζ)-potential, yield, entrapment efficiency, and drug loading capacity of the SQ-PLGA NPs. SQ-PLGA NPs were characterized by NTA, FE-SEM, and UV-Vis spectroscopy and the ability to produce reactive oxygen species (ROS) was evaluated, proving that ROS generation ability is preserved in SQ-PLGA. In vitro antimicrobial activity against Gram-positive bacteria in planktonic state using Staphylococcus aureus was conducted in different conditions and pH to evaluate the potential of these nanophotosensitizers for aPDT in the local treatment of infections.

Polymethine dyes for PDT: recent advances and perspectives to drive future applications.

It has been proved that the effectiveness of photodynamic therapy (PDT) is closely related to the intrinsic features of the photosensitizer (PS). Over the recent years, several efforts have been devoted to the discovery of novel and more efficient photosensitizers showing higher efficacy and lower side effects. In this context, squaraine and cyanine dyes have been reported to potentially overcome the drawbacks related to the traditional PSs. In fact, squaraines and cyanines are characterized by sharp and intense absorption bands and narrow emission bands with high extinction coefficients typically in the red and near-infrared region, good photo and thermal stability and a strong fluorescent emission in organic solvents. In addition, biocompatibility and low toxicity make them suitable for biological applications. Despite these interesting intrinsic features, their chemical instability and self-aggregation properties in biological media still limit their use in PDT. To overcome these drawbacks, the self-assembly and incorporation into smart nanoparticle systems are forwarded promising approaches that can control their physicochemical properties, providing rational solutions for the limitation of free dye administration in the PDT application. The present review summarizes the latest advances in squaraine and cyanine dyes for PDT application, analyzing the different strategies, i.e.the self-assembly and the incorporation into nanoparticles, to further enhance their photochemical properties and therapeutic potential. The in vivo assessments are still limited, thus further delaying their effective application in PDT.