Photodynamic therapy of melanoma by blue-light photoactivation of flavin mononucleotide

Abstract

Melanoma is one of the most aggressive and lethal form of cancer. Photodynamic therapy (PDT) is a clinically approved technique for cancer treatment, including non-melanoma skin cancer. However, the most of conventional photosensitizers are of low efficacy against melanoma due to the possible dark toxicity at high drug concentrations, melanin pigmentation, and induction of anti-oxidant defense mechanisms. In the current research we propose non-toxic flavin mononucleotide (FMN), which is a water-soluble form of riboflavin (vitamin B2) as a promising agent for photodynamic therapy of melanoma. We demonstrated selective accumulation of FMN in melanoma cells in vivo and in vitro in comparison with keratinocytes and fibroblasts. Blue light irradiation with dose 5 J/cm 2 of melanoma cells pre-incubated with FMN led to cell death through apoptosis. Thus, the IC 50 values of human melanoma A375, Mel IL, and Mel Z cells were in a range of FMN concentration 10–30 µM that can be achieved in tumor tissue under systemic administration. The efficiency of reactive oxygen species (ROS) generation under FMN blue light irradiation was measured in single melanoma cells by a label-free technique using an electrochemical nanoprobe in a real-time control manner. Melanoma xenograft regression in mice was observed as a result of intravenous injection of FMN followed by blue-light irradiation of tumor site. The inhibition of tumor growth was 85–90% within 50 days after PDT treatment.

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“…Although melanoma is a rare kind of tumor, it is one of the highly aggressive and lethal cancers with a mortality rate of 80% of the total number of skin cancers due to its high metastasis and acquired chemoresistance. 2,27 The primary treatments of melanoma are surgery, chemotherapy and radiotherapy, of which may face the dilemma of limited treatment ranges and serious side effects. 2 However, skin melanoma also shows the ability of light illuminate, making PDT a promising treatment.…”

“…At the same time, PDT can further prevent tumor recurrence by stimulating the body's immune system to produce tumor immune memory. 27 Furthermore, the combination of traditional treatments and PDT can further reduce drug use and avoid potential side effects while ensuring efficacy. Unlike photothermal agents that have both elevated temperatures and the ability to generate singlet oxygen, [29][30][31] photosensitizers are generally considered to have only the ability to produce singlet oxygen unless they possess particular morphological features.…”

Proof-of-Concept Study of Multifunctional Hybrid Nanoparticle System Combined with NIR Laser Irradiation for the Treatment of Melanoma

“…HaCat [44] and A375 [45] cells are known for their high expression of EGFR while, in contrast, B16F10 cells express low levels of this receptor [46]. Furthermore, the three cell lines have been associated with the presence of CD44 membrane receptors [47], with the lowest expression in HaCat cells and the highest in B16F10 cells. Cell lines were grown in DMEM with glucose (4500 mg/L), supplemented with 10% FBS and 100 IU/mL penicillin and 100 µg/mL streptomycin (Invitrogen; complete medium).…”

Deciphering UV‐induced DNA Damage Responses to Prevent and Treat Skin Cancer

“…For melanoma, PDT has had limited success, and resistance to PDT has been observed (223). A recent study demonstrated that flavin mononucleotide, which is a water‐soluble form of riboflavin (vitamin B 2 ), selectively accumulated in melanoma cells and suppressed tumor growth in a mouse xenograft model (224).…”