Delivery of miR-320a-3p by gold nanoparticles combined with photothermal therapy for directly targeting Sp1 in lung cancer,Biomaterials Science

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Delivery of miR-320a-3p by gold nanoparticles combined with photothermal therapy for directly targeting Sp1 in lung cancer
Biomaterials Science ( IF 5.8 ) Pub Date : 2021-08-13 , DOI: 10.1039/d1bm01124c
Jiefei Peng ₁ , Ranran Wang ₂ , Wanru Sun ₂ , Minhua Huang ₁ , Rong Wang ₃ , Youjie Li ₁ , Pingyu Wang ₄ , Guangbin Sun ₁ , Shuyang Xie _{1,

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Affiliation

Lung cancer is the second most common tumor and has the highest mortality rate. Both novel therapeutic targets and approaches are needed to improve the overall survival of patients with lung cancer. MicroRNA-320a-3p belongs to the miR-320a family and has been reported as a tumor suppressor in multiple cancers. However, its definitive role and precise mechanism in the progression of lung cancer remain unclear. In this study, we developed a new type of gold nanorod modified with polyethyleneimine that targets cancer-specific nanoparticles by RGD peptide, which could condense miRNA to self-assemble supramolecular nanoparticles. The designed nanoparticles can achieve integrin αvβ3-targeted cancer therapy, realize photosensitive therapy by laser irradiation and attain gene-targeted therapy by miRNAs. These nanoparticles could deliver miR-320a into lung cancer cells specifically and efficiently. Moreover, we demonstrated that Au-RGD-miR-320a nanoparticles combined with laser irradiation dramatically inhibited the proliferation and metastasis, and enhanced the apoptosis of lung cancer, both in vitro and in vivo. In terms of the mechanism, miR-320a inhibits Sp1 expression by directly binding to the 3′UTR of Sp1, and it eventually enhanced the expression of PTEN and inhibited the expression of matrix metallopeptidase 9 (MMP9). These findings provide a new and promising anticancer strategy via the use of Au-RGD-miR-320a nanoparticles, and identify miR-320a/Sp1 as a potential target for future systemic therapy against lung cancer.

中文翻译：

金纳米粒子递送miR-320a-3p联合光热疗法直接靶向肺癌中的Sp1

肺癌是第二常见的肿瘤，死亡率最高。需要新的治疗靶点和方法来提高肺癌患者的总体生存率。 MicroRNA-320a-3p 属于 miR-320a 家族，已被报道为多种癌症的肿瘤抑制因子。然而，其在肺癌进展中的明确作用和精确机制仍不清楚。在这项研究中，我们开发了一种用聚乙烯亚胺修饰的新型金纳米棒，通过RGD肽靶向癌症特异性纳米颗粒，它可以凝结miRNA以自组装超分子纳米颗粒。设计的纳米颗粒可以实现整合素αvβ3靶向癌症治疗、通过激光照射实现光敏治疗以及通过miRNA实现基因靶向治疗。这些纳米颗粒可以特异性、高效地将 miR-320a 递送到肺癌细胞中。此外，我们证明 Au-RGD-miR-320a 纳米颗粒与激光照射相结合，在体外和体内均显着抑制肺癌的增殖和转移，并增强肺癌的细胞凋亡。从机制上看，miR-320a通过直接结合Sp1的3'UTR来抑制Sp1的表达，最终增强PTEN的表达并抑制基质金属肽酶9（MMP9）的表达。这些发现通过使用 Au-RGD-miR-320a 纳米颗粒提供了一种新的、有前景的抗癌策略，并将 miR-320a/Sp1 确定为未来肺癌全身治疗的潜在靶点。

更新日期：2021-08-20

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