响应细胞内信号（例如 pH）的纳米材料具有许多生物医学应用的潜力，例如药物输送，因为可以定制组装/拆卸过程以响应特定亚细胞位置的刺激特征。在这项工作中，开发了两种罗丹明肽，它们在生理pH下形成稳定的纳米管，但在内体/溶酶体细胞区室的酸化内部解离成高荧光单体。显示了罗丹明二肽缀合物 NH2-KK(RhB)-NH2 (RhB-KK) 和 NH2-EK(RhB)-NH2 (RhB-KE)，其中赖氨酸残基的 ε-氨基位置附加了罗丹明 B 发色团在 pH 值高于 ~4-5 时组装成明确的纳米管，并在较低 pH 值下解离成荧光单体状态。使用圆二色性 (CD) 和荧光光谱以及透射电子显微镜 (TEM)、原子力显微镜 (AFM) 和共焦成像研究了组装过程的 pH 依赖性。虽然两种肽的罗丹明发色团的开环/闭环转变发生在 pH 4.1 时，但 RhB-KE 的组装开始于 pH 4.6，RhB-KK 的组装开始于相对更碱性的 pH (5.8)。因此，罗丹明肽在三种 pH 依赖性状态之间相互转化：pH 值等于或低于 4.6 时，开环单体状态（λmax 580 nm，λex 550 nm）；闭环纳米管形式，在较高 pH 值下表现出 AIEE（λmax 460 nm，λex = 330 nm）；低于临界胶束浓度 (CMC) 时出现的闭环、非发射单体状态。使用共焦激光扫描显微镜 (CLSM) 对三种癌细胞系进行活细胞成像，评估了肽的 pH 响应特征。与 RhB-KE 或 RhB-KK 孵育后对细胞进行可视化，产生 CLSM 图像，在与溶酶体共定位的德克萨斯红通道中具有点状外观。这些实验表明，纳米管被快速运输到细胞内的酸性溶酶体区室中，从而诱导解离成单体的开放状态。摄取抑制研究表明，细胞摄取是由小凹或网格蛋白介导的内吞作用介导的，具体取决于所研究的细胞系。

Nanomaterials that respond to intracellular signals, such as pH, have the potential for many biomedical applications, such as drug delivery, because the assembly/disassembly process can be tailored to respond to a stimulus characteristic of a specific subcellular location. In this work, two rhodamine-peptides that form stable nanotubes at physiological pH but dissociate into highly fluorescent monomers within the acidified interior of endosomal/lysosomal cellular compartments have been developed. The rhodamine dipeptide conjugates, NH2-KK(RhB)-NH2 (RhB-KK) and NH2-EK(RhB)-NH2 (RhB-KE) with rhodamine B chromophores appended at the ε-amino position of a lysine residue, were shown to assemble into well-defined nanotubes at pH values above ∼4-5 and to dissociate into a fluorescent monomer state at lower pH values. The pH dependence of the assembly process was investigated using circular dichroism (CD) and fluorescence spectroscopy along with transmission electron microscopy (TEM), atomic force microscopy (AFM), and confocal imaging. Although the ring opening/closing transition of the rhodamine chromophore took place at pH 4.1 for both peptides, the onset of assembly began at pH 4.6 for RhB-KE and at a comparatively more basic pH (5.8) for RhB-KK. Accordingly, the rhodamine-peptides interconverted between three pH-dependent states: an open-ring, monomeric state (λmax 580 nm, λex 550 nm) at pH values at or below ∼4.6; a closed-ring, nanotube form that exhibits AIEE (λmax 460 nm, λex = 330 nm) at higher pH values; a closed-ring, nonemissive monomeric state that emerged below the critical micelle concentrations (CMC). The pH-responsive features of the peptides were evaluated by live-cell imaging in three cancer cell lines using confocal laser scanning microscopy (CLSM). Visualizing the cells after incubation with either RhB-KE or RhB-KK produced CLSM images with a punctate appearance in the Texas Red channel that colocalized with the lysosomes. These experiments indicate that the nanotubes were rapidly trafficked into the acidic lysosomal compartments within the cells, which induced dissociation into a monomeric, open state. Uptake inhibition studies suggested that cellular uptake was mediated by either caveolae- or clathrin-mediated endocytosis, depending on the cell line studied.