Enhanced penetrative siRNA delivery by a nanodiamond drug delivery platform against hepatocellular carcinoma 3D models,Nanoscale

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Enhanced penetrative siRNA delivery by a nanodiamond drug delivery platform against hepatocellular carcinoma 3D models
Nanoscale ( IF 5.8 ) Pub Date : 2021-09-20 , DOI: 10.1039/d1nr03502a
Jingru Xu _{1,

2} , Mengjie Gu _{1,

2} , Lissa Hooi ₂ , Tan Boon Toh ₃ , Dexter Kai Hao Thng ₂ , Jhin Jieh Lim ₂ , Edward Kai-Hua Chow _{1,

2,

3,

4,

5,

6}

Affiliation

Small interfering RNA (siRNA) can cause specific gene silencing and is considered promising for treating a variety of cancers, including hepatocellular carcinoma (HCC). However, siRNA has many undesirable physicochemical properties that limit its application. Additionally, conventional methods for delivering siRNA are limited in their ability to penetrate solid tumors. In this study, nanodiamonds (NDs) were evaluated as a nanoparticle drug delivery platform for improved siRNA delivery into tumor cells. Our results demonstrated that ND-siRNA complexes could effectively be formed through electrostatic interactions. The ND-siRNA complexes allowed for efficient cellular uptake and endosomal escape that protects siRNA from degradation. Moreover, ND delivery of siRNA was more effective at penetrating tumor spheroids compared to liposomal formulations. This enhanced penetration capacity makes NDs ideal vehicles to deliver siRNA against solid tumor masses as efficient gene knockdown and decreased tumor cell proliferation were observed in tumor spheroids. Evaluation of ND-siRNA complexes within the context of a 3D cancer disease model demonstrates the potential of NDs as a promising gene delivery platform against solid tumors, such as HCC.

中文翻译：

通过纳米金刚石药物递送平台增强穿透性 siRNA 递送对抗肝细胞癌 3D 模型

小干扰 RNA (siRNA) 可导致特定基因沉默，被认为有望用于治疗多种癌症，包括肝细胞癌 (HCC)。然而，siRNA 有许多不利的理化性质，限制了其应用。此外，传递 siRNA 的常规方法在穿透实体瘤的能力方面受到限制。在这项研究中，纳米金刚石 (NDs) 被评估为一种纳米颗粒药物递送平台，用于改善 siRNA 向肿瘤细胞的递送。我们的结果表明，ND-siRNA 复合物可以通过静电相互作用有效地形成。ND-siRNA 复合物允许有效的细胞摄取和内体逃逸，从而保护 siRNA 免于降解。此外，与脂质体制剂相比，siRNA 的 ND 递送在穿透肿瘤球体方面更有效。这种增强的穿透能力使 NDs 成为针对实体瘤块传递 siRNA 的理想载体，因为在肿瘤球体中观察到有效的基因敲低和肿瘤细胞增殖的减少。在 3D 癌症疾病模型背景下对 ND-siRNA 复合物的评估证明了 ND 作为对抗实体瘤（如 HCC）的有前途的基因递送平台的潜力。

更新日期：2021-09-20

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