Abstract
Photodynamic Therapy (PDT), an unconventional cancer therapy with optimistic desirable effects, utilizes the delivery of a photosensitizer (PS) that is activated by light at a particular wavelength and inducing oxidative cytotoxic damage of a tumor and its surrounding vasculature. Deeper seated tumors such as internally metastasized melanomas are more difficult to treat with PDT as the penetration of laser light to those sites is less. Limitations in targeting melanomas can also be attributed to melanin pigments that hinder laser light from reaching targeted sites. Exosomes serve as naturally occurring nanoparticles that can be re-assembled with PSs, improving targeted cellular absorption of photosensitizing agents during PDT. Additionally, studies indicate that exosomes released from PDT-treated tumor cells play a critical role in mediating anti-tumor immune responses. This review collates the role of Melanoma Cell-Derived Exosomes (MTEX) in immune response mediation and metastasis. Tumor Cell-Derived Exosomes (TEX) post PDT treatment are also reviewed, as well as the effects of exosomes as carriers of photosensitizers and delivery systems for PDT. The understanding and research on the role of melanoma exosomes induced by Photodynamic Therapy and their tumor microenvironment will assist in future research in treatment prospects and implications.
Highlights
The prevalence of melanoma is on the rise and older population are mainly affected with an increased incidence later in life
Several other proteins like tyrosinase-related protein 2 (TYRP2), very late antige-4 (VLA-4), heat shock protein 70 (Hsp-70), major histocompatibility complex (MHC) I, melanoma antigen recognized by T cells 1 (Mart-1), mitogen-activated protein kinase kinase kinase kinase (MAPK4K), from human epidermal growth factor receptor 2 (Her2/neu), transient receptor potential (TRP), cluster of differentiation (CD)44, guanosne-50 -triphosphate (GTP)-binding proteins, annexin A2, disintegrin and metalloproteinase domain-containing protein 10 (ADAM10), and glycoprotein 100 (GP100) are seen enhanced in exosomes acquired from malignant melanoma, possibly serving as prognostic biomarkers [33,37,38]
The data from this study suggests that profuse extracellular vesicles (EVs) secretion prompted by non-severe cytotoxic therapy has the potential of exacerbating tumor conditions in cancer patients
Summary
The prevalence of melanoma is on the rise and older population are mainly affected with an increased incidence later in life. Treatment of tumor cells with PDT results in irreparable destruction of tumor cells and tumor-associated blood vessels. It is responsible for triggering antitumor, immune, and inflammatory responses. Exosomes are the smallest subset of bilayer extracellular vesicles (EV) occurring in all body fluids, and are manufactured by all cells undergoing physiological and pathological conditions. They function as components that engage a crucial role in the intercellular communication network. Exosomes that are re-assembled with PS have been reported to successfully deliver PS into target cells and generate the required, effective amount of reactive oxygen species (ROS) when exposed to laser treatment for photodynamic therapy [4]. Early and late onset side effects, including other limitations must be studied
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