Metformin-loaded bioinspired mesoporous silica nanoparticles for targeted melanoma therapy: Nanotopographical design with in vitro and in vivo evaluation

Omar A. ElkadyMai A. ZaafanMarian GeorgeNadeen Ashraf ElsayedVerina Ghaly MettiasVerina Sameh EdwardDina Saeed Ghataty2025-04-022025-04-022025-03-23Elkady, O. A., Zaafan, M. A., George, M., Elsayed, N. A., Mettias, V. G., Edward, V. S., & Ghataty, D. S. (2025b). Metformin-loaded bioinspired mesoporous silica nanoparticles for targeted melanoma therapy: Nanotopographical design with in vitro and in vivo evaluation. International Journal of Pharmaceutics, 125499. https://doi.org/10.1016/j.ijpharm.2025.125499https://doi.org/10.1016/j.ijpharm.2025.125499https://repository.msa.edu.eg/handle/123456789/6367Q1Bioinspired nanotopographical carriers have emerged as innovative cancer therapy strategies, mimicking natural processes to enhance targeted delivery and reduce systemic toxicity. This study presents the development of virus-like mesoporous silica nanoparticles (MSN) as a delivery platform for repurposed metformin (MTF) in a topical multi-stimuli responsive system for melanoma treatment. Metformin-loaded virus-like MSN (MTF-MSN) were fabricated and incorporated into a thermo-responsive gelling system. The particles were evaluated for morphology, zeta potential (ZP), particle size (PS), entrapment efficiency (EE%), Fourier-transform infrared (FTIR) spectroscopy, MTT cytotoxicity assay, in vitro release, and in a melanoma in vivo model. The particles exhibited a spherical morphology, a zeta potential of +31.9 ± 1.45 mV, and a particle size of 197 ± 3.47 nm, ideal for skin penetration. MTF-MSN demonstrated significant antiproliferative activity against melanoma A375 cells, with lower IC50 values (192 μg/mL) compared to free MTF (>300 μg/mL). Sustained, pH-sensitive MTF release was observed over 48 h at pH 7.4 and 6 h at pH 5.5. In vivo studies showed enhanced anti-cancer efficacy of MTF-MSN, evidenced by elevated caspase-3 and Neurofibromin Type-1 (NF-1) levels, along with suppressed angiogenesis markers VEGF and NRAS. The MTF-MSN-treated group exhibited superior outcomes compared to free MTF and controls (p < 0.05). This innovative bioinspired MTF-MSN hydrogel system optimizes MTF delivery for melanoma therapy, pioneering advancements in drug repurposing and nano-oncology.en-USBioinspired nanotopographyMelanomaMesoporous silicaMetforminMulti-stimuli responsiveMetformin-loaded bioinspired mesoporous silica nanoparticles for targeted melanoma therapy: Nanotopographical design with in vitro and in vivo evaluationArticlehttps://doi.org/10.1016/j.ijpharm.2025.125499