Abstract
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.Graphical abstract
Highlights
The origin of photodynamic therapy (PDT), originally known as heliotherapy, dates back to ancient civilizations such as Egypt, Greece, China, Rome and India [1, 2]
Despite the evident limits of squaraines and cyanines, we have shown their efficacy as alternative promising photosensitizers to treat cancer diseases
We have covered several topics ranging from a structure–activity analysis of the polymethine dyes described in literature as PDT photosensitizers to different approaches to overcome their limitations to boost their knowledge and the spreading of their use in PDT
Summary
The origin of photodynamic therapy (PDT), originally known as heliotherapy, dates back to ancient civilizations such as Egypt, Greece, China, Rome and India [1, 2]. The first generation includes porphyrins (Photofrin®) and chlorins, which have been widely clinically used in the treatments of lung, esophagus, pancreatic and bladder cancer Despite their efficacy, some specific drawbacks related to hydrophobicity in biological microenvironment, non-specificity and poor tissue penetration due to light absorption at a specific spectral region led to the development of the second-generation photosensitizers (derivatives of chlorins, i.e Foscan®, bacteriochlorins, and phthalocyanines). They can be synthesized with absorbance bands between 600 and 800 nm, perfectly fitting the phototherapeutic window, and the procedure to produce them allow to obtain a single pure compound under good manufacturing practice (GMP) conditions with quality control and low manufacturing costs. The overall recent in vivo studies on both cyanines and squaraines will be reported in the fourth and last sections, highlighting the lack of in vivo works and the limitation of the use of PMDs in therapeutic application
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