Light‐Activated Biomedical Applications of Chlorophyll Derivatives

Abstract

Tetrapyrroles are the basis of essential physiological functions in most living organisms. These compounds represent the basic scaffold of porphyrins, chlorophylls, and bacteriochlorophylls, among others. Chlorophyll derivatives, obtained by the natural or artificial degradation of chlorophylls, present unique properties, holding great potential in the scientific and medical fields. Indeed, they can act as cancer‐preventing agents, antimutagens, apoptosis inducers, efficient antioxidants, as well as antimicrobial and immunomodulatory molecules. Moreover, thanks to their peculiar optical properties, they can be exploited as photosensitizers for photodynamic therapy and as vision enhancers. Most of these molecules, however, are highly hydrophobic and poorly soluble in biological fluids, and may display undesired toxicity due to accumulation in healthy tissues. The advent of nanomedicine has prompted the development of nanoparticles acting as carriers for chlorophyll derivatives, facilitating their targeted administration with demonstrated applicability in diagnosis and therapy. In this review, the chemical and physical properties of chlorophyll derivatives that justify their usage in the biomedical field, with particular regard to light‐activated dynamics are described. Their role as antioxidants and photoactive agents are discussed, introducing the most recent nanomedical applications and focusing on inorganic and organic nanocarriers exploited in vitro and in vivo.

Development of organic photosensitizers for antimicrobial photodynamic therapy

“…37 Examples of chlorophyll photosensitizers include temoporfin, p-bro-mo-phenylhydrazone-methyl pyropheophorbide-a, chlorophyll-a, pheophorbide a, and chlorin e6 (Ce6). [55][56][57] Among these, Ce6 is a potent photosensitizer that has a wide range of applications in PDT, but its development has been hindered due to its poor water solubility and easy removal. 58 To improve the efficiency of PDT in treating skin knife injury infection caused by Gram-negative bacteria, Fu's group constructed a novel polymer micelle (Pep@Ce6) with bacterialtargeting and photosensitizer loading capacity (Fig.…”

“…37 Examples of chlorophyll photosensitizers include temoporfin, p -bro-mo-phenylhydrazone-methyl pyropheophorbide-a, chlorophyll-a, pheophorbide a, and chlorin e6 (Ce6). 55–57 Among these, Ce6 is a potent photosensitizer that has a wide range of applications in PDT, but its development has been hindered due to its poor water solubility and easy removal. 58…”

Recent advances in anti-multidrug resistance for nano-drug delivery system

“…At the same time, anticancer drug cisplatin is released from Pt (IV) moieties with GSH reduction response (Zeng et al., 2020 ). Porohyrinoid-based photosensitizers are the most common and abundance photosensitizers, which are the framework of chlorophyll (Pucci et al., 2021 ). The four nitrogen atoms of porphyrinioids can complex various metal cations, which will dramatically affect ROS generation (Otvagin et al., 2022 ).…”

Water-Soluble Porphyrin-Based Nanoparticles Derived from Electrostatic Interaction for Enhanced Photodynamic Therapy

“…Cancer, as one of the deadliest diseases threatening the health of human beings, has cost huge financial resources annually in the search for and improvement of its treatment. Instead of traditional cancer therapies, including chemotherapies, radiotherapies, and surgery, photodynamic therapy (PDT) is more harmless to the human body and has minimal side effects because of its superior tissue penetration and selective killing of cancer cells. − Photosensitizers, light, and oxygen are three key components of PDT treatment. Photosensitizers enable the production of reactive oxygen species (ROS) including singlet oxygen ( 1 O 2 ) through the irradiation of near-infrared light, which contributes to tumor destruction by leading to cell apoptosis and necrosis in diseased tissue.…”