The good, the bad, and the ugly–controlling singlet oxygen through design of photosensitizers and delivery systems for photodynamic therapy

Abstract

Singlet oxygen, although integral to photodynamic therapy, is notoriously uncontrollable, suffers from poor selectivity and has fast decomposition rates in biological media. Across the scientific community, there is a conscious effort to refine singlet oxygen interactions and initiate selective and controlled release to produce a consistent and reproducible therapeutic effect in target tissue. This perspective aims to provide an insight into the contemporary design principles behind photosensitizers and drug delivery systems that depend on a singlet oxygen response or controlled release. The discussion will be accompanied by in vitro and in vivo examples, in an attempt to highlight advancements in the field and future prospects for the more widespread application of photodynamic therapy.

Enhancement of Photodynamic Cancer Therapy by Physical and Chemical Factors

“…Using nanosized carriers for photosensitizer delivery is atechnique that is turning out desirable results,improving the capability of photodynamic activity while overcoming many side effects. [28] Using nanosized carriers has been found beneficial in many ways.F irst, the photosensitizer itself usually does not have tumor-targeting capability,b ut it can always be loaded in ananocarrier that is modified by tumorhoming motifs,s uch as tumor-homing peptides.N amely,t he tumor-targeting nanocarriers have the ability to home into tumor tissues and assist in concentrating the photosensitizer there;this helps minimize the harmful effects of treatment to healthy tissues,making PDT amore desirable option. Second, unlike many other nanoformulated chemotherapeutics,p ayload bioavailability and efficacyd ifficulties are avoided by containing the photosensitizer within nanoparticles,s uch as mesoporous silica nanoparticles (MSNs) and activating them via an external source.T hus it is reasonable to suggest that specifically delivering photosensitizer by way of nanocarriers could improve PDT.…”

Optimierung photodynamischer Krebstherapien auf der Grundlage physikalisch‐chemischer Faktoren

“…[28] Der Einsatz von Nanoträgern hat sich auf vielfältige Weise als vorteilhaft erwiesen. [28] Der Einsatz von Nanoträgern hat sich auf vielfältige Weise als vorteilhaft erwiesen.…”

“…Die Anwendung von nanoskaligen Tr ägern fürd en Tr ansport von Photosensibilisatoren an Tumoren hat das Potenzial, photodynamische Aktivitäten zu verbessern und dabei zahlreiche Nebenwirkungen zu vermeiden. [28] Der Einsatz von Nanoträgern hat sich auf vielfältige Weise als vorteilhaft erwiesen. Zum einen hat der Photosensibilisator selbst normalerweise nicht die Fähigkeit, einen Tumor anzusteuern.…”

Development of Prodrugs for PDT-Based Combination Therapy Using a Singlet-Oxygen-Sensitive Linker and Quantitative Systems Pharmacology

“…More recent approaches have been designed to minimize systemic adverse effects of anticancer drugs based on various innovative ideas [12,20,26,27]. Reactive oxygen species were also used for triggering drug release from stimuli-responsive drug-releasing systems [28][29][30][31][32]. In our lab, we have been developing such prodrug systems in which the anticancer drug is released from the inert species were also used for triggering drug release from stimuli-responsive drug-releasing systems [28][29][30][31][32].…”