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.

Metastatic melanoma cancer stem cells are subpopulations that have been identified and linked to tumor progression, immunoevasive behavior, drug resistance, and metastasis, leading to a poor prognosis. Photodynamic therapy (PDT) is an approach to eradicate cancer through a photochemical process which directly generates reactive oxygen species (ROS). This study investigated the impact of PDT using an aluminum phthalocyanine gold nanoparticle (AlPcS₄Cl-AuNP) conjugate for targeting melanoma stem cells. The isolated stem cells were irradiated at 673.2 nm with a radiant exposure of 5 J/cm². Post-irradiation signs of cell death were determined using microscopy and biochemical assays. A possible enhanced effect of ROS in inducing cell death could be seen when AlPcS₄Cl was conjugated to AuNPs. Nanoparticles as carriers promote the efficient cellular uptake of photosensitizers, enhancing organelle accumulation and the targeted therapy of cancerous cells. A biochemical assay revealed significant post-irradiation signs of cell death. The measurement of adenosine triphosphate (ATP) content revealed a decrease in cell proliferation. The study suggested an approach directed at expanding the knowledge on PDT to improve cancer treatment. Understanding the cell death mechanism through which ROS influence cancer stem cells (CSCs) is, therefore, useful for improving PDT efficiency and preventing tumor recurrence and metastasis.