State Key Laboratory of Molecular Engineering of Polymers, Fudan University, No.220, Handan Road, Shanghai, China.
Department of Macromolecular Science, Fudan University, No.2005, Songhu Road, Shanghai, China.
Nat Commun. 2024 Oct 8;15(1):8699. doi: 10.1038/s41467-024-53053-3.
Polymer nanoparticles that can sharply sense and detect biological signals in cells are promising candidates for biomedical and theranostic nanomaterials. However, the response ability of current polymer assemblies poorly matches the requirement of trace concentration level (10 ~ 10mol/L) of cellular biosignals due to their linear signal input-to-function output mode, which impedes their practical applications in vivo. Here we report a kind of nanobowl system with pH-tunable invaginated morphology that can nonlinearly amplify the response abilities toward biosignals by modulating the surface concavity. Compared to conventional spherical nanoparticles, nonspherical nanobowls with a specific concave structure reduce the critical response threshold of polymers by up to 5 orders of magnitude, from millimole to nanomole level, covering most of biosignal concentration windows. Moreover, we find that this nonlinear signal gain effect is originated from the collective impact of a single signal on transitioning the polymer chain aggregation state of individual assemblies, rather than just altering a certain unit or chain. This nonlinear signal-to-response mechanism is potential to solve the tricky problems of probing and sensing endogenous signals with trace physiological concentration.
能够敏锐感知和检测细胞内生物信号的聚合物纳米粒子是生物医学和治疗性纳米材料的有前途的候选者。然而，由于其线性信号输入-功能输出模式，当前聚合物组装体的响应能力与细胞生物信号的痕量浓度水平（10~10mol/L）的要求相差甚远，这阻碍了它们在体内的实际应用。在这里，我们报告了一种具有 pH 可调内陷形态的纳米碗系统，通过调节表面凹度，可以非线性地放大对生物信号的响应能力。与传统的球形纳米粒子相比，具有特定凹面结构的非球形纳米碗将聚合物的临界响应阈值降低了多达 5 个数量级，从毫摩尔降低到纳摩尔水平，覆盖了大多数生物信号浓度窗口。此外，我们发现这种非线性信号增益效应源于单个信号对单个组装体的聚合物链聚集状态转变的集体影响，而不仅仅是改变某个单元或链。这种非线性的信号-响应机制有望解决探测和感测具有痕量生理浓度的内源性信号的棘手问题。
