Does Encapsulation of π‐Conjugated Polymer Nanoparticles within Biodegradable PEG–PLGA Matrices Mitigate Photoinduced Free Radical Production and Phototoxicity?

Lipophilic π‐conjugated polymers (CPs) encapsulated within self‐assembling diblock copolymer poly(ethylene glycol) methyl ether‐block‐poly(lactide‐co‐glycolide) (PEG–PLGA) nanoparticles, are interesting candidates for photodynamic and photothermal therapies. Upon irradiation, CPs generate reactive oxygen species (ROS), which may either cause local phototoxicity or could be exploited for photodynamic therapy. The propensity of the PEG–PLGA matrix to scavenge ROS has never been investigated. Here the ability of two PEG–PLGA structures (PEG2 kDa–PLGA4.5 kDa vs PEG5 kDa–PLGA55 kDa) to mitigate the release of ROS generated by four different CPs (PFO, F8BT, CN‐PPV, and PCPDTBT) following irradiation (5 J cm−2) at 385, 455, and 656 nm is studied. The molar content of the PEG–PLGA matrix, rather than the molecular weight or composition, appeared to be the most influential factor, i.e., lower molar concentrations of the matrix polymer are associated with significant increases in phototoxicity. Multivariate analysis reveals that the combination of CP photophysical properties and nanoparticle matrix properties are important for understanding CP nanoparticle‐induced phototoxicity.