The Therapeutic Revolution of Conjugated Polymer Nanoparticles in Photodynamic Therapy and Photodynamic Inactivation

Abstract

Compared to traditional anticancer and antimicrobial therapies, photodynamic therapy (PDT) and photodynamic inactivation (PDI) arise as improved treatment tools due to their highly effective, non-invasive and localized therapeutic action. These therapies simultaneously combine three elements: i) photosensitizer (PS), ii) light and iii) molecular oxygen to produce reactive oxygen species (ROS). These oxygen species can produce biomolecular damage that leads to eukaryotic and prokaryotic cell death. Moreover, nanotechnology has been used for light-mediated anticancer and antibacterial strategies to overcome inherent limitations of small molecule PSs, such as poor solubility in biological media, nontargeted delivery, and inefficient photoinduced generation of ROS. In this sense, conjugated polymer nanoparticles (CPNs) have emerged as advanced PSs used in PDT and PDI treatments. Conjugated polymers (CP) are organic macromolecules formed by a series of repetitive monomers concatenated together by a succession of single and double (or triple) bonds alternated along the chain. The polymer main chain has segments of variable length where the delocalization of the π electrons is preserved acting as “quasi-chromophores.” CPNs are formed by folding/collapsing of CP hydrophobic chains in a poor solvent (water) to form nanoaggregates. These nanoaggregates act as densely packed multichromophoric systems with exceptional light harvesting and (intraparticle) energy transfer capabilities which can lead to efficient photosensitized formation of ROS when effectively exploited. Additionally, CPNs have a number of properties which are highly desirable for PDT, PDI and theranostics applications, such as small size (10-50 nm) with narrow distribution, nearly null cytotoxicity, high fluorescence brightness, large absorption coefficients of one and twophotons, and easily tuned optical and photochemical properties by the incorporation of molecular dopants. A brief review of the literature shows that CPNs have been increasingly used as advanced PSs for cell labeling, anticancer treatment (PDT), and bacterial inactivation (PDI). This chapter aims to summarize recent advances, mainly from our laboratory, on the development of CPNs as advanced PSs for PDT and PDI applications.