Challenges to perform an efficiently gene therapy adopting non-viral vectors: Melanoma landscape

Viegas, Juliana Santos Rosa; Bentley, Maria Vitória Lopes Badra; Vicentini, Fabiana T. M. C.

doi:10.1016/j.jddst.2022.103964

Cited by 4 publications

(1 citation statement)

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“…The delivery system, such as nanoparticles, as non-viral vectors for nucleic acids, presents promising results in cancer treatment, including melanoma [10], highlighting the co-deliver drugs and nucleic acids, such as siRNAs [1,9].…”

Section: Introductionmentioning

confidence: 99%

Bcl-2 knockdown by multifunctional lipid nanoparticle and its influence in apoptosis pathway regarding cutaneous melanoma: in vitro and ex vivo studies.

Viegas,

Araujo,

Leite

et al. 2024

Preprint

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Multifunctional therapies have emerged as innovative strategies in cancer treatment. In this research article, we proposed a nanostructured lipid carrier (NLC) designed for the topical treatment of cutaneous melanoma, which simultaneously delivers 5-FU and Bcl-2 siRNA. The characterized nanoparticles exhibited a diameter of 259 ± 9 nm and a polydispersion index of 0.2, indicating a uniform size distribution. The NLCs were primarily localized in the epidermis, effectively minimizing the systemic release of 5-FU across skin layers. The ex vivo skin model revealed the formation of a protective lipid film, decreasing the desquamation process of the stratum corneum which can be associated to an effect of increasing permeation. In vitro assays demonstrated that A375 melanoma cells exhibited a higher sensitivity to the treatment compared to non-cancerous cells, reflecting the expected difference in their metabolic rates. The uptake of NLC by A375 cells reached approximately 90% within 4 hours. The efficacy of Bcl-2 knockdown was thoroughly assessed using ELISA, Western blot, and qRT-PCR analyses, revealing a significant knockdown and synergistic action of the NLC formulation containing 5-FU and Bcl-2 siRNA (at low concentration --100 pM). Notably, the silencing of Bcl-2 mRNA also impacted other members of the Bcl-2 protein family, including Mcl-1, Bcl-xl, BAX, and BAK. The observed modulation of these proteins strongly indicated the activation of the apoptosis pathway, suggesting a successful inhibition of melanoma growth and prevention of its in vitro spread.

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Section: Introductionmentioning

confidence: 99%