Transdermal hyaluronate/cationic solid lipid nanoparticle/siRNA complex for the treatment of skin cancer

IF 10.5 1区医学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Journal of Controlled Release Pub Date : 2025-06-23 DOI:10.1016/j.jconrel.2025.113967

Zhengyu Piao, Mungu Kim, Jin Huh, Sei Kwang Hahn

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Abstract

Lipid nanoparticles (LNPs) are widely recognized for their potential in drug delivery. However, they exhibit significant limitations in stability and targeting. In this study, we designed a target-specific siRNA delivery system by coating hyaluronate (HA) onto cationic solid lipid nanoparticles (CSLNs). The angiogenesis-inhibiting siVEGF formed a stable nanoscale complex for the targeted delivery to skin cancer tissue. The nucleic acid drug in the HA/CSLN/siVEGF complex was electrostatically coated on the surface of CSLN, enabling high drug loading capacity. Moreover, HA appeared to serve a dual purpose in this design by targeting to cancer cells and facilitating effective transdermal delivery. The optimized HA/CSLN/siVEGF complex resulted in facilitated transdermal delivery, effective tumor targeting, and significantly reduced VEGF mRNA levels, leading to tumor growth inhibition. Taken together, the HA/CSLN complex would be successfully harnessed as a transdermal target-specific delivery carrier of siRNA for cancer therapy.

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透皮透明质酸/阳离子固体脂质纳米颗粒/siRNA复合物治疗皮肤癌

脂质纳米颗粒（LNPs）因其在药物传递方面的潜力而被广泛认可。然而，它们在稳定性和靶向性方面表现出明显的局限性。在这项研究中，我们设计了一种靶向siRNA递送系统，通过将透明质酸（HA）涂覆在阳离子固体脂质纳米颗粒（csln）上。抑制血管生成的siVEGF形成了稳定的纳米级复合物，用于靶向递送到皮肤癌组织。HA/CSLN/siVEGF复合物中的核酸药物被静电包被在CSLN表面，具有较高的载药能力。此外，透明质酸在这种设计中似乎具有双重目的，即靶向癌细胞和促进有效的透皮递送。优化后的HA/CSLN/siVEGF复合物可促进经皮给药，有效靶向肿瘤，并显著降低VEGF mRNA水平，从而抑制肿瘤生长。综上所述，HA/CSLN复合物将成功地作为siRNA的透皮靶向递送载体用于癌症治疗。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Controlled Release 医学-化学综合

CiteScore

18.50

自引率

5.60%

发文量

700

审稿时长

39 days

期刊介绍： The Journal of Controlled Release (JCR) proudly serves as the Official Journal of the Controlled Release Society and the Japan Society of Drug Delivery System. Dedicated to the broad field of delivery science and technology, JCR publishes high-quality research articles covering drug delivery systems and all facets of formulations. This includes the physicochemical and biological properties of drugs, design and characterization of dosage forms, release mechanisms, in vivo testing, and formulation research and development across pharmaceutical, diagnostic, agricultural, environmental, cosmetic, and food industries. Priority is given to manuscripts that contribute to the fundamental understanding of principles or demonstrate the advantages of novel technologies in terms of safety and efficacy over current clinical standards. JCR strives to be a leading platform for advancements in delivery science and technology.