Photodynamic therapy (PDT) combines a light source with a light-activated “photosensitive compound" to generate reactive oxygen species (ROS) that selectively damage targets like bacteria, fungi, parasites, or cancer cells [1,2]. It is a modern and non-invasive therapy that enables the selective destruction of inappropriate cell types [3] while striving to preserve healthy tissue [1].
Methylene blue (MB) is a dye with well-understood chemistry that goes back over a century. It has emerged as a practical, low-cost photosensitizer for skin conditions because it absorbs red light efficiently, works in oxygenated skin, and clears quickly, which limits prolonged photosensitivity. Early clinical studies and case reports have suggested benefits for acne, chronic wounds, cancer, localized psoriasis plaques, some nail disorders, cutaneous leishmaniasis, and possibly superficial fungal infections [4-6]. Although this evidence is promising, there is still a lack of clarity on the specific dose and technique across conditions.
In this article, we will examine the pairing of PDT and MB, provide an overview of how this combination works, and assess its potential applications in skincare.
How does methylene blue work with photodynamic therapy (MB-PDT)?
MB is a cationic phenothiazine dye that absorbs light strongly around 660-670 nm. This is right in the “optical window” where red light can penetrate several millimeters into the skin. When illuminated, excited MB transfers energy to oxygen to produce singlet oxygen and other ROS. These short-lived ROS damage membranes, proteins, and nucleic acids in the vicinity.
In dermatology, this enables antimicrobial action against acne, Staphylococcus aureus (including MRSA), dermatophytes/yeasts, and some protozoa [7]. It also leverages cytotoxicity against abnormal skin cells in plaque psoriasis [8,9] or dysregulated inflammatory environments. Because ROS acts locally and MB clears quickly, systemic side effects are uncommon with topical use.
Most studies activate MB with red LEDs or lasers near 670 nm, sometimes with intense pulsed light (IPL). Typical fluences range widely (e.g., 5-20 J/cm² in plaque psoriasis trials), with exposure times of several minutes per session. The ideal protocol is not yet standardized and varies by indication, formulation, and device power.
Where is MB-PDT being used?
The bacteria that cause acne are photosensitive and located deep inside hair follicles. Red light can reach them, and MB can concentrate around the bacterial membrane. Small studies have shown that MB-assisted PDT can reduce inflammatory lesion counts more than light alone, although the protocols used make direct comparisons between studies difficult [10,11].
Chronic and infected wounds, such as those laden with biofilms, are hard to treat, yet PDT holds promise for disrupting biofilms while sparing the local tissue. Case reports and prospective studies show that MB-PDT reduced odor, exudate, and wound size, with patients generally tolerating treatment well and experiencing few adverse effects [12,13].
PDT can also modulate hyperproliferative keratinocytes and local inflammation, such as that seen in plaque psoriasis. MB-PDT may be considered for problematic, well-demarcated plaques in patients who want to avoid systemic therapy, yet understand that evidence is preliminary and sessions may need repeating [9].
How does MB-PDT align with other photosensitizers?
ALA/PpIX-PDT (5-aminolevulinic acid) is widely used for actinic keratoses and some acne regimens, but it often causes pain, requires long incubations, and can lead to transient photosensitivity and post-inflammatory hyperpigmentation. MB, by contrast, is water-soluble, inexpensive, rapidly cleared, and can be used with shorter incubations and LEDs that many clinics already possess. The trade-off is that MB can stain skin temporarily, and there is a smaller evidence base, with broad variability in concentration, incubation, and fluence across protocols.
Safety, side effects, and contraindications
With topical use, adverse effects are usually mild. These include temporary blue staining, transient erythema, warmth, or tingling during illumination. Compared to ALA-PDT, pain scores are often lower.
Importantly, systemic MB (e.g., intravenous for methemoglobinemia) has well-known risks such as serotonin syndrome due to MAO-inhibition when combined with serotonergic drugs, hemolysis in G6PD deficiency, and paradoxical oxidant stress at high doses. While these are far less likely with topical dermatologic doses, it’s prudent to screen for G6PD deficiency, pregnancy, and serotonergic polypharmacy, especially if treating large areas of skin or damaged skin where absorption could increase.
In a wound series using MB-PDT, investigators reported no significant local reactions (e.g., burning, pruritus) and good tolerability, but sample sizes were small. As with any light-based procedure, one should avoid treating tattooed areas without counseling about temporary discoloration and also consider post-procedure sun protection [12,14].
Limitations of the research
The parameters used in the current evidence are heterogeneous and therefore restrict comparisons. There are broad differences in concentrations, incubation times, fluences, session counts, and light sources. The evidence is also limited by the small sample sizes of studies, and the durability of the technique beyond a few months is not clear. MB is approved for systemic indications (e.g., methemoglobinemia), but MB-PDT for skin is an off-label or investigational use in many jurisdictions, so local regulations must be taken into account [6].
The future of MB-PDT research
Emerging research is pairing MB with nanoparticles, flexible liposomes, and hybrid polymers to increase delivery to follicles, biofilms, and parasites while minimizing off-target staining. Others are refining LED dosimetry and fractionated light schedules to balance efficacy and comfort. As device costs fall and home-use LEDs proliferate, interest in protocolized, clinic-supervised regimens will likely grow. This is provided that larger, controlled trials confirm the early signals seen in acne, wounds, and localized psoriasis.
Conclusion
Methylene blue-mediated photodynamic therapy is an accessible, versatile approach with real-world momentum in dermatology for acne, infected and chronic wounds, stubborn psoriatic plaques, and selected infections. The mechanistic fit is promising, as MB absorbs red light efficiently and generates ROS in the vicinity of skin conditions. Clinical evidence is encouraging but contingent on getting the details aligned, such as formulation, concentration, incubation, wavelength, fluence, and session cadence.
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Read more on methylene blue and skin below:
References
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