DNA mechanocapsules for programmable piconewton responsive drug delivery.
DNA mechanocapsules for programmable piconewton responsive drug delivery.
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DOI：
10.1038/s41467-023-44061-w
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发表时间：
2024-01-24
影响因子：
16.6
通讯作者：
Salaita, Khalid
中科院分区：
文献类型：
--
作者：
Velusamy, Arventh;Sharma, Radhika;Rashid, Sk Aysha;Ogasawara, Hiroaki;Salaita, Khalid
细胞的机械失调与许多疾病状态相关，从纤维化到肿瘤发生。因此，非常需要开发基于细胞的“机械表型”递送药物的策略。为了实现这一目标，我们报告的DNA机械胶囊（DMC）的发展组成的DNA四面体是力响应。建模显示了力诱导DMC破裂的轨迹，并预测了施加的力的空间位置和方向如何调整力响应阈值。用粘附配体官能化的DMC由于细胞受体力而在体外机械变性。DMC被设计成包封大分子货物，如葡聚糖和寡核苷酸药物，具有最小的货物泄漏和高核酸酶抗性。使用流式细胞术验证DMC货物的力诱导的释放和摄取。最后，我们证明了力诱导的HIF-1α mRNA敲低的方式是依赖于细胞牵引力的大小。这些结果表明，DMC可以有效地用于靶向生物物理表型，这可能在免疫学和癌症生物学中找到有用的应用。细胞的机械失调与几种疾病相关，并且期望基于细胞的“机械表型”递送药物的策略。在这里，作者设计和表征了由力响应的DNA四面体组成的DNA机械胶囊，并表明它们可以封装大分子货物并在施加力时释放它。
The mechanical dysregulation of cells is associated with a number of disease states, that spans from fibrosis to tumorigenesis. Hence, it is highly desirable to develop strategies to deliver drugs based on the “mechanical phenotype” of a cell. To achieve this goal, we report the development of DNA mechanocapsules (DMC) comprised of DNA tetrahedrons that are force responsive. Modeling shows the trajectory of force-induced DMC rupture and predicts how applied force spatial position and orientation tunes the force-response threshold. DMCs functionalized with adhesion ligands mechanically denature in vitro as a result of cell receptor forces. DMCs are designed to encapsulate macromolecular cargos such as dextran and oligonucleotide drugs with minimal cargo leakage and high nuclease resistance. Force-induced release and uptake of DMC cargo is validated using flow cytometry. Finally, we demonstrate force-induced mRNA knockdown of HIF-1α in a manner that is dependent on the magnitude of cellular traction forces. These results show that DMCs can be effectively used to target biophysical phenotypes which may find useful applications in immunology and cancer biology. The mechanical dysregulation of cells is associated with several diseases and strategies to deliver drugs based on the “mechanical phenotype” of a cell are desirable. Here, the authors design and characterize DNA mechanocapsules comprised of DNA tetrahedrons that are force responsive, and showed they can encapsulate macromolecular cargo and release it upon application of force.
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影响因子：
4
作者：
Bridgewater, Rebecca E.;Norman, Jim C.;Caswell, Patrick T.
通讯作者：
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影响因子：
48
作者：
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在生活/非生存界面处的张力传感纳米颗粒用于机械成像。
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通讯作者：
Salaita, Khalid
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作者：
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作者：
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通讯作者：
Roca-Cusachs P