Lipid nanoparticle-encapsulated cannabidiol enhances selective cytotoxicity in melanoma cells
DOI:
https://doi.org/10.48797/sl.2026.470Keywords:
PosterAbstract
Background: Melanoma is the most lethal form of skin cancer, accounting for approximately 325,000 new cases and 57,000 deaths worldwide in 2020 [1], with incidence projected to exceed 500,000 cases annually by 2040 [2]. Despite therapeutic advances, treatment remains limited by drug resistance and off-target toxicity. Cannabidiol (CBD) has shown promising anticancer potential [3,4]; however, its clinical use is hindered by poor physicochemical properties. Lipid nanoparticle-based delivery systems may overcome these limitations by enhancing CBD stability, cellular uptake, and tumor selectivity [5]. Objective: This study aims to evaluate the effect of CBD-loaded lipid nanoparticles (NP-CBD) on cell viability in metastatic melanoma (MeWo) and normal keratinocyte (HaCaT) cell lines, focusing on their ability to enhance cytotoxic efficacy and selectivity compared to free CBD. Methods: MeWo and HaCaT cells were exposed to increasing concentrations (0.05–100 μM) of free CBD or NP-CBD (mean diameter of 205.6 ± 3.4 nm) for 48 h. Cell viability was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay. Results: Free CBD induced a concentration-dependent reduction in cell viability in both MeWo and HaCaT cells, with comparable IC₅₀ values (4.6 µM and 3.9 µM, respectively), indicating limited selectivity toward tumor cells. In contrast, NP-CBD enhanced cytotoxic effects in MeWo cells (IC₅₀ 3.2 vs 4.6 µM, p = 0.0001), while significantly reducing toxicity in HaCaT keratinocytes (IC₅₀ 8.6 vs 3.9 µM, p < 0.0001). This resulted in a clear shift toward increased tumor cell sensitivity and a more favorable safety profile. Conclusions: Lipid nanoparticle encapsulation significantly improves the biological performance of CBD by enhancing its antitumor activity and selectivity. NP-CBD represents a promising nanotechnology-based strategy to optimize CBD delivery, supporting the development of more effective and less toxic therapeutic approaches for melanoma.References
1. De Pinto, G. et al. Global trends in cutaneous malignant melanoma incidence and mortality. Melanoma Res 2024, 34, 265-275, doi:10.1097/CMR.0000000000000959.
2. Arnold, M. et al. Global burden of cutaneous melanoma in 2020 and projections to 2040. JAMA Dermatol 2022, 15, 495-503, doi:10.1001/jamadermatol.2022.0160.
3. Seltzer, E.S. et al. Cannabidiol (CBD) as a promising anti-cancer drug. Cancers 2020, 12, 3203, doi:10.3390/cancers12113203.
4. Mashabela, M.D. et al. Anti-cancer and anti-proliferative potential of cannabidiol: A cellular and molecular perspective. Int J Mol Sci 2024, 25, 5659, doi:10.3390/ijms25115659.
5. Paczkowska-Walendowska, M. et al. Innovative strategies to enhance the bioavailability of cannabidiol: Nanotechnology and advanced delivery systems. Pharmaceuticals 2025, 18, 1637, doi: 10.3390/ph18111637.
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Copyright (c) 2026 Natanael Videira, Ana M. Araújo, Carla M. Lopes, Marlene Lúcio, Carolina Mota, José Catita, Márcia Carvalho
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