Enhanced Penetrability of a Tetrahedral Framework Nucleic Acid by Modification with iRGD for DOX-Targeted Delivery to Triple-Negative Breast Cancer,ACS Applied Materials & Interfaces

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Enhanced Penetrability of a Tetrahedral Framework Nucleic Acid by Modification with iRGD for DOX-Targeted Delivery to Triple-Negative Breast Cancer
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2021-05-26 , DOI: 10.1021/acsami.1c07297
Mengting Liu ₁ , Wenjuan Ma ₁ , Dan Zhao ₁ , Jiajie Li ₁ , Qirong Li ₁ , Yuhao Liu ₁ , Liying Hao ₁ , Yunfeng Lin _{1,

2}

Affiliation

Poor penetrability and nonselective distribution of chemotherapeutic drugs are the main obstacles for chemotherapy for triple-negative breast cancer (TNBC). In our work, we developed a DNA-based drug delivery system to surmount these barriers. In addition, a tetrahedral framework nucleic acid (tFNA) was employed to load doxorubicin (DOX) with iRGD decoration to form a novel nanoparticle (tFNA/DOX@iRGD). The RGD sequence and the CendR motif in iRGD are used in tumor targeting and tissue penetration, respectively. Based on the sustained serum stability and pH-sensitive release behavior of DOX, tFNA/DOX@iRGD exhibited superiority for biomedical application. Moreover, tFNA/DOX@iRGD showed excellent deep penetration and drug accumulation in three-dimensional (3D) multicellular tumor spheroids compared to DOX and tFNA/DOX. Additionally, the therapeutic effect was verified in a 4T1 subcutaneous tumor model, and the complexes displayed a superior antitumor and antiangiogenic efficiency with fewer collateral damages. Therefore, these findings suggested that tFNA/DOX@iRGD might be a more effective pattern for drug delivery and TNBC therapy.

中文翻译：

通过 iRGD 修饰增强四面体框架核酸的渗透性，用于 DOX 靶向递送至三阴性乳腺癌

化疗药物的渗透性差和非选择性分布是三阴性乳腺癌（TNBC）化疗的主要障碍。在我们的工作中，我们开发了一种基于 DNA 的药物输送系统来克服这些障碍。此外，采用四面体框架核酸 (tFNA) 加载具有 iRGD 修饰的阿霉素 (DOX) 以形成新型纳米颗粒 (tFNA/DOX@iRGD)。iRGD 中的 RGD 序列和 CendR 基序分别用于肿瘤靶向和组织穿透。基于 DOX 的持续血清稳定性和 pH 敏感释放行为，tFNA/DOX@iRGD 在生物医学应用方面表现出优越性。此外，与 DOX 和 tFNA/DOX 相比，tFNA/DOX@iRGD 在三维（3D）多细胞肿瘤球体中显示出优异的深度渗透和药物积累。此外，该治疗效果在 4T1 皮下肿瘤模型中得到验证，该复合物显示出优异的抗肿瘤和抗血管生成效率，且附带损伤较少。因此，这些发现表明 tFNA/DOX@iRGD 可能是一种更有效的药物递送和 TNBC 治疗模式。

更新日期：2021-06-09

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