Researchers from Wuhan University and City University of Hong Kong have reported a soft, transparent, and stretchable laser-induced graphene (LIG)-Cu/PDMS patch that delivers noninvasive, low-temperature photothermal therapy for melanoma while simultaneously activating multiple programmed cell death pathways.
Melanoma causes over 80% of skin cancer-related deaths, and its aggressiveness, metastasis and drug resistance limit conventional surgery and chemoradiotherapy. The new patch is a bandage-like construct in which CuO-embedded LIG acts as the active therapeutic layer and polydimethylsiloxane (PDMS) provides a biocompatible, breathable, conformable matrix. Chemically inert and soft on the skin, the LIG-Cu/PDMS hybrid is fabricated via a cold-transfer method, remaining transparent and stretchable and enabling intimate contact, repeated use and potentially prolonged Cu²⁺ release under controlled stimulation.
Under mild photothermal activation with simulated sunlight or a low-power laser, the LIG converts light to heat and raises the local temperature only to about 42 °C, high enough to activate the system but low enough to spare surrounding healthy tissue. At this temperature, Cu²⁺ is released from the CuO-filled porous graphene and accumulates in melanoma tissue directly beneath the patch rather than in major organs or blood, avoiding systemic copper retention and long-term toxicity. In vitro, this triggered release kills most melanoma cells and slows their migration; in a mouse model, two 1-hour phototherapy sessions (on days 1 and 5) achieved a 97% reduction of melanoma lesions within 10 days, without damage to adjacent skin.
Local copper accumulation and photothermal stimulation drive a burst of reactive oxygen species, causing mitochondrial oxidative stress and jointly activating apoptosis, cuproptosis and ferroptosis. In canonical cuproptosis, copper binds lipoylated TCA-cycle proteins, inducing their aggregation and mitochondrial dysfunction; the resulting damage amplifies ROS and lipid peroxidation, accelerating ferroptosis. The synergy of these pathways eradicates melanoma cells and promotes the release of tumor-associated antigens and damage-associated molecular patterns, which remodel the tumor immune microenvironment, boost systemic antitumor immunity and inhibit invasion and metastasis.
Operating under a strictly standardized mild photothermal regimen (≤42 °C), the reusable, noninvasive LIG-Cu/PDMS patch offers a controllable and reproducible platform that combines low-temperature photothermal therapy with multi-pathway cell death and immunomodulation. This establishes a promising paradigm for graphene-based biomedical materials in cancer, highlighting the translational potential of multifunctional patches for targeted, safe and efficient treatment of melanoma and other superficial tumors.
