Nanoparticle Beacons: Supersensitive Smart Materials with On/Off-Switchable Affinity to Biomedical Targets
Nanoparticle Beacons: Supersensitive Smart Materials with On/Off-Switchable Affinity to Biomedical Targets
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DOI：
10.1021/acsnano.9b07569
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发表时间：
2020-02-01
期刊：
影响因子：
17.1
通讯作者：
Nikitin, Maxim P.
中科院分区：
文献类型：
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作者：
Cherkasov, Vladimir R.;Mochalova, Elizaveta N.;Nikitin, Maxim P.
在化学触发器的影响下可以在不同状态之间切换的智能材料在生物医学中具有很高的需求，其中对生物标志物的特异性反应对于精确的诊断和治疗至关重要。药物递送至恶性细胞的上级选择性可以用保持“惰性”直到通过微环境线索的特征性分布（例如，肿瘤代谢物、血管生成因子、微小RNA/DNA等）。然而，尽管智能材料设计种类繁多且功能复杂，但其实际应用却因对输入的敏感度非常有限而受到阻碍。在这里，我们提出了超灵敏的智能nanoagents与输入依赖的开/关切换亲和力的生物医学目标的基础上结合的金纳米粒子与低能量聚合物结构。在所提出的方法中，基于纳米颗粒的试剂表面涂覆有定制设计的柔性聚合物链，该聚合物链具有可切换输入的结构，该结构调节用于靶结合的末端受体的可及性。用这种聚合物的DNA模型实施该概念已经产生了具有输入依赖性细胞靶向能力和在15分钟侧流测定中对低至30 fM的DNA输入的响应性的纳米剂。因此，我们表明，表面现象可以增强nanoagents与切换亲和力的能力，而不影响对输入的敏感性。所提出的方法是有希望的下一代治疗诊断剂和超灵敏的纳米传感器的即时诊断的发展。
Smart materials that can switch between different states under the influence of chemical triggers are highly demanded in biomedicine, where specific responsiveness to biomarkers is imperative for precise diagnostics and therapy. Superior selectivity of drug delivery to malignant cells may be achieved with the nanoagents that stay "inert" until "activation" by the characteristic profile of microenvironment cues (e.g., tumor metabolites, angiogenesis factors, microRNA/DNA, etc.). However, despite a wide variety and functional complexity of smart material designs, their real-life applications are hindered by very limited sensitivity to inputs. Here, we present ultrasensitive smart nanoagents with input-dependent On/Off switchable affinity to a biomedical target based on a combination of gold nanoparticles with low-energy polymer structures. In the proposed method, a nanoparticle-based agent is surface coated with a custom designed flexible polymer chain, which has an input-switchable structure that regulates accessibility of the terminal receptor for target binding. Implementation of the concept with a DNA-model of such polymer has yielded nanoagents that have input-dependent cell-targeting capabilities and responsiveness to as little as 30 fM of DNA input in 15 min lateral flow assay. Thus, we show that surface phenomena can augment nanoagents with capability for switchable affinity without compromising the sensitivity to inputs. The proposed approach is promising for development of next-generation theranostic agents and ultrasensitive nanosensors for point-of-care diagnostics.