Engineered Exosomes as a Photosensitizer Delivery Platform for Cancer Photodynamic Therapy

Abstract

Photodynamic therapy (PDT), a non‐/minimally invasive cancer treatment method, has the advantages of low side effects, high selectivity, and low drug resistance. It is currently a popular cancer treatment method. However, given the shortcomings of photosensitizers such as poor photostability, poor water solubility, and short half‐life in vivo when used alone, the development of photosensitizer nano‐delivery platforms has always been a research hotspot to overcome these shortcomings. In the human body, various types of cells generally release bilayer extracellular vesicles known as exosomes. Compared with traditional materials, exosomes are currently an ideal drug delivery platform due to their homology, low immunogenicity, easy modification, high biocompatibility, and natural carrying capacity. Therefore, in this concept, we focus on the research status and prospects of engineered exosome‐based photosensitizer nano‐delivery platforms in cancer PDT.

Wharton jelly-derived mesenchymal stem cell exosomes induce apoptosis and suppress EMT signaling in cervical cancer cells as an effective drug carrier system of paclitaxel

“…In the in vivo experiment, it has been shown that EXO-DTX has a higher drug potential than free DTX and can be used as a good carrier system due to its faster entry into cells [ 41 ]. It is even suggested that the problems of water solubility and photosensitivity can be solved by these transport systems by loading photosensitizer anti-cancer drugs into exosomes [ 42 , 43 ].…”

Engineered Exosome for Drug Delivery: Recent Development and Clinical Applications

“…Moreover, this method uses temperature differences to regulate drug loading and release rates, which enhances drug loading efficiency. 60 , 61 However, the shortages of this method are low production efficiency, exosome instability, and limited applicability. Besides, this method requires a long preparation time due to the continuous cooling and heating process, which may disrupt exosome stability and quality, causing the loss of their original function.…”

Engineered exosomes from different sources for cancer-targeted therapy

“…132 Activating ferroptosis inducer and photosensitizer carried by exosomes via laser irradiation could achieve synergetic antitumor effects. 132,133 Mounting evidence has shown ferroptosis could exhibit a pronounced therapeutic impact on plenty of solid tumors, such as gastric cancer, pancreatic cancer, CRC, and HCC particularly on apoptosis-resistant tumors. [134][135][136] Ferroptosis relies on irondependent Fenton reaction and the accumulation of lipid peroxides.…”

“…Another example of engineered exosome-based PDT is the dual-stage light-guided plasma membrane and nucleus-targeting photodynamic therapy. 133,142 Under the first-stage light, multifunctional chimeric peptide-engineered exosomes could directly disrupt the membrane structure and lead to cell death. Meanwhile, photochemical internalization (PCI) effects 143 and lysosomal escape 142 resulting from first-stage light would improve the cytosolic delivery of exosomes.…”