Topological structures of bio-architectonics and bio-interfaces play major roles in maintaining the normal functions of organs, tissues, extracellular matrix, and cells. In-depth understanding of natural self-assembly mechanisms and mimicking functional structures provide us opportunities to artificially control the natural assemblies and their biofunctions. Here, we report an intracellular enzyme-catalyzed polymerization approach for efficient synthesis of polypeptides and in situ construction of topology-controlled nanostructures. We reveal that the phase behavior and topological structure of polypeptides are encoded in monomeric peptide sequences. Next, we elucidate the relationship between polymerization dynamics and their temperature-dependent topological transition in biological conditions. Importantly, the linearly grown elastin-like polypeptides are biocompatible and aggregate into nanoparticles that exhibit significant molecular accumulation and retention effects. However, 3D gel-like structures with thermo-induced multi-directional traction interfere with cellular fates. These findings allow us to exploit new nanomaterials in living subjects for biomedical applications.

In situ construction of self-assemblies with unique property in living systems is a promising direction in the biomedical field. The noninvasive methods for significant enzyme activity in living cells or living subjects are imperative and meantime challenge tasks. The dynamic process of self-assembly of chlorophyll-based molecules in complex biological systems can be monitored by photoacoustic signals, which supports a noninvasive way to understand and quantitatively measure the activity of caspase-1. Furthermore, the activity of caspase-1 enables reflection of the bacterial infection in the early stage. Here, we present a biocompatible self-assembly from chlorophyll-peptide derivatives and first correlate the dynamic equilibrium with ratiometric photoacoustic signals. The intracellular equilibrium was managed by a bacterial infection precaution protein, i.e., caspase-1. This system offers a trial of noninvasive method to quantitative detection and real-time monitoring of bacterial infection in the early stage.

We demonstrate in situ construction and characterization of supramolecular aggregates from chlorin p6 (Cp6) molecules in tumor cells. Fully deprotonated Cp6 molecules in neutral condition were partially protonated inside the acidic lysosomes of cells and significantly increased the hydrophobicity of them that resulted in simultaneous formation of J-type aggregates. Importantly, the formation of J-aggregates was fully characterized in artificial tissues by UV-vis, circular dichroism (CD) and transmission electron microscope (TEM) techniques. Compared to the monomers, the J-aggregates exhibited 55-fold enhanced thermal conversion efficiency (η) at the optimal excitation wavelength (690 nm). The remarkably increased heat effect contributed to the stronger photoacoustic (PA) signals, leading to at least 2 orders of magnitude increase of the tumor-to-normal tissue ratio (T/N), which was defined as the PA signal ratio between tumor site and surrounding normal tissue. We envision that this proof-of-concept study will open a new way to develop tumor environment-induced self-assembly for variable biomedical applications.