Enhancing Fractionated Cancer Therapy: A Triple-Anthracene Photosensitizer Unleashes Long-Persistent Photodynamic and Luminous Efficacy

Abstract

Conventional photodynamic therapy (PDT) is often limited in treating solid tumors due to hypoxic conditions that impede the generation of reactive oxygen species (ROS), which are critical for therapeutic efficacy. To address this issue, a fractionated PDT protocol has been suggested, wherein light irradiation is administered in stages separated by dark intervals to permit oxygen recovery during these breaks. However, the current photosensitizers used in fractionated PDT are incapable of sustaining ROS production during the dark intervals, leading to suboptimal therapeutic outcomes (Table S1). To circumvent this drawback, we have synthesized a novel photosensitizer based on a tripleanthracene derivative that is designed for prolonged ROS generation, even after the cessation of light exposure. Our study reveals a unique photodynamic action of these derivatives, facilitating the direct and effective disruption of biomolecules and significantly improving the efficacy of fractionated PDT (Table S2). Moreover, the existing photosensitizers lack imaging capabilities for monitoring, which constraints the fine-tuning of irradiation parameters (Table S1). Our triple-anthracene derivative also serves as an afterglow imaging agent, emitting sustained luminescence postirradiation. This imaging function allows for the precise optimization of intervals between PDT sessions and aids in determining the timing for subsequent irradiation, thus enabling meticulous control over therapy parameters. Utilizing our novel tripleanthracene photosensitizer, we have formulated a fractionated PDT regimen that effectively eliminates orthotopic pancreatic tumors. This investigation highlights the promise of employing long-persistent photodynamic activity in advanced fractionated PDT approaches to overcome the current limitations of PDT in solid tumor treatment.

Lysosomal-targeted fluorescent probe based pH regulating reactivity for tracking cysteine dynamics under oxidative stress

“…20–22 As a novel imaging method, in recent years, fluorescence imaging technology has become the “eye” to reveal the relationship between a signal molecule and the specific disease because of its advantages of visualization and endogenous imaging. 23–28 For timely detection of lysosomal cystine transport abnormalities, it is important to develop a reversible fluorescent probe for the real-time detection of the concentration changes of Cys in lysosomes.…”

A Novel Boron Dipyrromethene-Erlotinib Conjugate for Precise Photodynamic Therapy against Liver Cancer

“…In practice, the type II mechanism is more dominant than the type I mechanism, with most currently available PSs, such as porphyrins and phthalocyanines, operating on this principle [4]. It is noteworthy that the short lifespan (ranging from 30 to 180 nanoseconds) and limited migration distance (less than 100 nanometers) 2 of 14 of the ROS ensure that PDT is only effective within the irradiated area by light, which endows PDT with high spatial selectivity [5]. This precision is a significant advantage of PDT, as it allows for targeted treatment of tumors while minimizing damage to adjacent healthy tissue.…”