Chhibber Tanya, Scherzer Michael T, Prokofyeva Anastasia, Becker Carly, Zitnay Rebecca Goldstein, Smith Eric, Khurana Nitish, Skliar Mikhail, Deacon Dekker C, VanBrocklin Matthew W, Ghandehari Hamidreza, Judson-Torres Robert L, Jafari Paris
Department of Molecular Pharmaceutics, University of Utah, Salt Lake City, UT 84112, USA; Utah Center for Nanomedicine, University of Utah, Salt Lake City, UT 84112, USA.
Huntsman Cancer Institute, Salt Lake City, UT, USA.
J Control Release. 2025 May 10;381:113586. doi: 10.1016/j.jconrel.2025.113586. Epub 2025 Mar 1.
Small non-coding RNAs (e.g., siRNA, miRNA) are involved in a variety of melanocyte-associated skin conditions and act as drivers for alterations in gene expression within melanocytes. These molecular changes can potentially affect the cellular stability of melanocytes and promote their oncogenic transformation. Thus, small RNAs can be considered as therapeutic targets for these conditions, however, their transdermal delivery to the melanocytes through the epidermal barrier is challenging. We synthesized and extensively evaluated ultradeformable cationic liposome (UCLs) carriers complexed with synthetic microRNAs (miR211-5p; UCL-211) for transdermal delivery to melanocytes. UCL-211 complexes were characterized for their physicochemical properties, encapsulation efficiency, and deformability, which revealed a significant advantage over conventional liposomal carriers. Increased expression of miR211-5p stabilizes melanocytic nevi and keeps them in a growth-arrested state. We did a comprehensive assessment of cellular delivery, and biological activity of the miR211-5p carried by UCL-211 in vitro and their permeation through the epidermis of intact skin using ex vivo human skin tissue explants. We also demonstrated, in vivo, that transdermal delivery of miR211-5p by topical application of UCL-211 stabilized BRAFV600E+ nevi melanocytes in a benign nevi state.
小型非编码RNA（例如，小干扰RNA、微小RNA）参与多种与黑素细胞相关的皮肤疾病，并作为黑素细胞内基因表达改变的驱动因素。这些分子变化可能会影响黑素细胞的细胞稳定性，并促进其致癌转化。因此，小RNA可被视为这些疾病的治疗靶点，然而，通过表皮屏障将它们经皮递送至黑素细胞具有挑战性。我们合成并广泛评估了与合成微小RNA（miR211-5p；UCL-211）复合的超可变形阳离子脂质体（UCLs）载体，用于经皮递送至黑素细胞。对UCL-211复合物的物理化学性质、包封效率和变形性进行了表征，结果显示其相对于传统脂质体载体具有显著优势。miR211-5p表达的增加可使黑素细胞痣稳定，并使其处于生长停滞状态。我们对UCL-211携带的miR211-5p在体外的细胞递送和生物活性以及它们通过离体人皮肤组织外植体完整皮肤表皮的渗透进行了全面评估。我们还在体内证明，通过局部应用UCL-211经皮递送miR211-5p可使BRAFV600E+痣黑素细胞稳定在良性痣状态。
