Photoresponsive miR-34a/Nanoshell Conjugates Enable Light-Triggered Gene Regulation to Impair the Function of Triple-Negative Breast Cancer Cells,Nano Letters

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Photoresponsive miR-34a/Nanoshell Conjugates Enable Light-Triggered Gene Regulation to Impair the Function of Triple-Negative Breast Cancer Cells
Nano Letters ( IF 9.6 ) Pub Date : 2020-12-11 , DOI: 10.1021/acs.nanolett.0c03152
Megan N Dang ₁ , Carolina Gomez Casas ₁ , Emily S Day _{1,

2,

3}

Affiliation

Triple-negative breast cancer (TNBC) is an aggressive disease that requires new interventions. A promising approach to improve patient prognosis is to introduce tumor suppressive miR-34a into TNBC cells. Unfortunately, naked miR-34a is not effective therapeutically because it is degraded by nucleases and cannot passively enter cells. Nanocarriers designed to increase miR-34a stability and cellular entry have lacked specificity and potency. To overcome these limitations, we conjugated miR-34a to photoresponsive gold nanoshells (NS), which can release tethered miR-34a upon excitation with continuous wave (CW) or nanosecond (ns) pulsed near-infrared light to facilitate on-demand gene regulation. We demonstrate that miR-34a/NS can regulate downstream miR-34a targets following irradiation to reduce TNBC cell viability, proliferation, and migration. Further, we show ns pulsed light releases miRNA more effectively than CW light, and that released miR-34a is as potent as transfected miR-34a. These findings signify miR-34a/NS as promising tools for precisely controlled gene regulation of TNBC.

中文翻译：

光响应 miR-34a/纳米壳缀合物能够通过光触发基因调控来损害三阴性乳腺癌细胞的功能

三阴性乳腺癌（TNBC）是一种侵袭性疾病，需要新的干预措施。改善患者预后的一种有前景的方法是将肿瘤抑制性 miR-34a 引入 TNBC 细胞。不幸的是，裸露的miR-34a在治疗上并不有效，因为它会被核酸酶降解并且不能被动地进入细胞。旨在提高 miR-34a 稳定性和细胞进入能力的纳米载体缺乏特异性和效力。为了克服这些限制，我们将 miR-34a 与光响应金纳米壳 (NS) 结合，在连续波 (CW) 或纳秒 (ns) 脉冲近红外光激发下可以释放束缚的 miR-34a，以促进按需基因调控。我们证明 miR-34a/NS 可以在照射后调节下游 miR-34a 靶标，从而降低 TNBC 细胞的活力、增殖和迁移。此外，我们发现 ns 脉冲光比 CW 光更有效地释放 miRNA，并且释放的 miR-34a 与转染的 miR-34a 一样有效。这些发现表明 miR-34a/NS 作为精确控制 TNBC 基因调控的有前途的工具。

更新日期：2021-01-13

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