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Review
. 2022 Sep 27:10:1032318.
doi: 10.3389/fbioe.2022.1032318. eCollection 2022.

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

Lingjun Tong  1 , Sitong Zhang  2   3 , Rong Huang  1 , Huaxi Yi  4 , Jiong-Wei Wang  2   3   5   6
Affiliations
Review

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

Lingjun Tong et al. Front Bioeng Biotechnol. .

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.

Keywords: drug delivery system; extracellular vesicle; nanoparticle; photodynamic therapy; photosensitizer.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Biogenesis of the three major categories of extracellular vesicles. MVB, multivesicular bodies. Figure was prepared with BioRender®.
FIGURE 2
FIGURE 2
Strategies for loading photosensitizers into EVs. Figure was prepared with BioRender®.
FIGURE 3
FIGURE 3
EVs from multiple cell sources as photosensitizer carriers for photodynamic therapy. (A) ZnPc was incorporated into EVs derived from immune cells (M1 or M2 like macrophages), cancer cells (B16F10 melanoma cancer cells), or external sources (milk), by a direct incubation strategy. (B) Therapeutic efficacy of photosensitizer-based delivery systems in cancer (Huis In 't Veld et al., 2022). Copyright 2022 BMC.
FIGURE 4
FIGURE 4
Engineered multi-functional EV delivery platforms for photodynamic therapy. (A) Illustration of AIEgens-loaded EV delivery system for promoting efficient tumor penetration and photodynamic therapy (Zhu et al., 2020). (B) Schematic illustration of tumor-derived EVs co-delivering AIEgens and proton pump inhibitors for tumor glutamine starvation therapy and enhanced type-I PDT (Zhu et al., 2022). Copyright 2022 German Chemical Society and Elsevier.
See this image and copyright information in PMC

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