Recent advances in optimizing siRNA delivery to hepatocellular carcinoma cells.

IF 5.4 Expert opinion on drug delivery Pub Date : 2025-05-01 Epub Date: 2025-03-30 DOI:10.1080/17425247.2025.2484287
Ralf Weiskirchen, Sabine Weiskirchen, Chiara Grassi, Bruna Scaggiante, Mario Grassi, Domenico Tierno, Alice Biasin, Nhung Hai Truong, Thanh Dang Minh, Maja Cemazar, Giorgia Pastorin, Federica Tonon, Gabriele Grassi
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Abstract

Introduction: Hepatocellularcarcinoma (HCC), the primary form of liver cancer, is the second leading cause of cancer-related deaths worldwide. Current therapies have limited effectiveness, particularly in advanced stages of the disease, highlighting the need for innovative treatment options. Small-interfering RNA(siRNA) molecules show great promise as a therapeutic solution since they can inhibit the expression of genes promoting HCC growth. Their cost-effective synthesis has further encouraged their potential use as novel drugs. However, siRNAs are vulnerable to degradation in biological environments, necessitating protective delivery systems. Additionally, targeted delivery to HCC is critical for optimal efficacy and minimal undesired side effects.

Areacovered: This review addresses the challenges associated with the delivery of siRNA toHCC, discussing and focusing on delivery systems based on lipid and polymeric nanoparticles in publications from the past five years.

Expert opinion: Future nano particles will need to effectively cross the vessel wall, migrate through the extracellular matrix and finally cross the HCC cell membrane. This may be achieved by optimizing nanoparticle size, the equipment of nanoparticles withHCC targeting moieties and loading nanoparticles with siRNAs againstHCC-specific oncogenes.

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优化肝癌细胞 siRNA 传输的最新进展。
肝细胞癌(HCC)是肝癌的主要形式,是全球癌症相关死亡的第二大原因。目前的治疗方法有效性有限,特别是在疾病的晚期,这突出了创新治疗方案的必要性。小干扰RNA(siRNA)分子可以抑制促进HCC生长的基因的表达,因此作为一种治疗方案具有很大的前景。它们具有成本效益的合成进一步鼓励了它们作为新药的潜在用途。然而,sirna在生物环境中容易降解,因此需要保护性的递送系统。此外,靶向给药对于获得最佳疗效和最小化不良副作用至关重要。涵盖领域:本综述解决了与siRNA递送至hcc相关的挑战,讨论并关注了过去五年发表的基于脂质和聚合物纳米颗粒的递送系统。专家意见:未来的纳米颗粒需要有效地穿过血管壁,通过细胞外基质迁移,最终穿过HCC细胞膜。这可以通过优化纳米颗粒的大小、靶向hcc的纳米颗粒的设备以及装载靶向thcc特异性癌基因的sirna来实现。
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