Piao Zhengyu, Kim Mungu, Huh Jin, Hahn Sei Kwang
Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam-ro, Nam-gu, Pohang, Gyeongbuk 37673, Republic of Korea.
Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam-ro, Nam-gu, Pohang, Gyeongbuk 37673, Republic of Korea.
J Control Release. 2025 Sep 10;385:113967. doi: 10.1016/j.jconrel.2025.113967. Epub 2025 Jun 23.
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.
脂质纳米颗粒（LNPs）因其在药物递送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存在显著局限性。在本研究中，我们通过将透明质酸（HA）包覆在阳离子固体脂质纳米颗粒（CSLNs）上，设计了一种靶向特异性siRNA递送系统。抑制血管生成的siVEGF形成了一种稳定的纳米级复合物，用于靶向递送至皮肤癌组织。HA/CSLN/siVEGF复合物中的核酸药物通过静电作用包覆在CSLN表面，从而实现高药物负载量。此外，HA在该设计中似乎具有双重作用，既能靶向癌细胞，又能促进有效的透皮递送。优化后的HA/CSLN/siVEGF复合物实现了促进透皮递送、有效肿瘤靶向，并显著降低了VEGF mRNA水平，从而抑制肿瘤生长。综上所述，HA/CSLN复合物将成功用作siRNA的透皮靶向特异性递送载体用于癌症治疗。
