Tumor-Targeting Cholesterol-Decorated DNA Nanoflowers for Intracellular Ratiometric Aptasensing.
Tumor-Targeting Cholesterol-Decorated DNA Nanoflowers for Intracellular Ratiometric Aptasensing.
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DOI：
10.1002/adma.202007738
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发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
Stevens MM
中科院分区：
文献类型：
--
作者：
Kim N;Kim E;Kim H;Thomas MR;Najer A;Stevens MM
探测内源性分子特征对理解细胞功能和过程具有重要意义。尽管基于可编程核酸的适体传感器有望在生物分子检测的范围内实现，但能够实现细胞内检测的目标响应型适体传感器尚不常见。仍然存在一些挑战，包括基于淬火器的强度信号的量化/归一化困难，探针结构的稳定性问题，以及复杂的传感器操作通常需要广泛的结构建模。在这里，我们提出了仿生结晶授权的肿瘤靶向dna -无机杂交纳米复合适体传感器的自组装，该传感器能够Förster共振能量转移为基础的定量解释细胞靶标丰度的变化。利用滚圆放大驱动DNA纳米结构的设计可编程性和高通量制造，我们的设计平台提供了一种从多功能编码模板自组装健壮的纳米传感器的方法，该模板包括细胞靶向适体、比例适体传感器和胆固醇修饰元件。以前列腺癌细胞和细胞内三磷酸腺苷分子为模型系统，我们证明了胆固醇和适体在靶向递送中的协同作用，以及细胞内适体化定量的可行性。我们设想，我们的方法在不同的目标系统中提供了一种高度通用的策略，以实现生物可交付的比例适体传感器，从而方便地监测内源性生物分子的丰度。
Probing endogenous molecular profiles is of fundamental importance to understanding cellular function and processes. Despite the promise of programmable nucleic acid-based aptasensors across the breadth of biomolecular detection, target-responsive aptasensors enabling intracellular detection are as of yet infrequently realized. Several challenges remain, including the difficulties in quantification/normalization of quencher-based intensiometric signals, stability issues of the probe architecture, and complex sensor operations often necessitating extensive structural modeling. Here, we present the biomimetic crystallization-empowered self-assembly of a tumor-targetable DNA-inorganic hybrid nanocomposite aptasensor that enables Förster resonance energy transfer-based quantitative interpretation of changes in the cellular target abundance. Leveraging the design programmability and high-throughput fabrication of rolling circle amplification-driven DNA nanoarchitecture, our designer platform offers a method to self-assemble a robust nanosensor from a multifunctionality-encoded template that includes a cell-targeting aptamer, a ratiometric aptasensor, and a cholesterol-decorating element. Taking prostate cancer cells and intracellular adenosine triphosphate molecules as a model system, we demonstrate a synergistic effect in the targeted delivery by cholesterols and aptamers, and the feasibility of quantitative intracellular aptasensing. We envision that our approach provides a highly generalizable strategy across a diverse range of target systems toward a biologically deliverable ratiometric aptasensor, enabling facile monitoring of abundance of endogenous biomolecules.
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