Extracellular vesicles as a novel photosensitive drug delivery system for enhanced photodynamic therapy

Abstract

Photodynamic therapy (PDT) is a promising non-invasive therapeutic approach that utilizes photosensitizers (PSs) to generate highly reactive oxygen species (ROS), including singlet oxygen, for removal of targeted cells. PDT has been proven efficacious for the treatment of several diseases, including cancer, cardiovascular disease, inflammatory bowel disease, and diabetic ocular disease. However, the therapeutic efficacy of PDT is limited and often accompanied by side effects, largely due to non-specific delivery of PSs beyond the desired lesion site. Over the past decade, despite various nanoparticular drug delivery systems developed have markedly improved the treatment efficacy while reducing the off-target effects of PSs, concerns over the safety and toxicity of synthetic nanomaterials following intravenous administration are raised. Extracellular vesicles (EVs), a type of nanoparticle released from cells, are emerging as a natural drug delivery system for PSs in light of EV’s potentially low immunogenicity and biocompatibility compared with other nanoparticles. This review aims to provide an overview of the research progress in PS delivery systems and propose EVs as an alternative PS delivery system for PDT. Moreover, the challenges and future perspectives of EVs for PS delivery are discussed.

Photodynamic Therapy for Inflammatory and Cancerous Diseases of the Intestines: Molecular Mechanisms and Prospects for Application

“…Therefore, developing innovative strategies to enhance PS delivery is of paramount importance 179 . To overcome the challenges associated with direct PS administration, researchers have explored carrier-mediated delivery systems such as liposomes 180 , aggregation-induced emission (AIE) luminogen hybrid nanovesicles 181 , and extracellular vehicles (EVs) 182 to facilitate PS transport to target cells. Liposomes, which are spherical vesicles composed of lipid bilayers closely resembling biological membranes, serve as versatile carriers for PS 183 .…”

“…Sonodynamic therapy involves the use of ultrasound in combination with a sonosensitizer to induce the production of reactive oxygen species and achieve tumor destruction 182 . When combined with PDT, sonodynamic therapy can further enhance the cytotoxic effects on tumor cells 195 .…”

Bacterial outer membrane vesicles as drug delivery carrier for photodynamic anticancer therapy

“…In addition, some modified nanomaterials can be responsive to the physiological characteristics of the tumor (e.g., enzyme and pH) and their microenvironment (e.g., hypoxia, GSH, hydrogen sulfide, H 2 O 2 , and H + ) or externally applied physical stimuli (e.g., light, heat, ultrasound) to realize controlled release of PSs at specific sites ( Zheng et al, 2020 ). However, scholars have raised concerns about biological toxicity, biodegradability, safety, immunogenicity, and tolerance of these nanomaterials after intravenous administration ( Tong et al, 2022 ). These uncertainties limit the vast majority of research on the nanomaterials-based-delivery system of PSs to preclinical studies, which is a big challenge for them in achieving clinical conversion.…”