General Approach of Stimuli-Induced Aggregation for Monitoring Tumor Therapy

Intracellular construction of nanoaggregates from synthetic molecules to mimic natural ordered superstructures has gained increasing attention recently. Here, we develop an endogenous stimuli-induced aggregation (eSIA) approach to construct functional nanoaggregates for sensing and monitoring cellular physiological processes in situ. We design a series of thermosensitive polymer-peptide conjugates (PPCs), which are capable of constructing nanoaggregates in cells based on their isothermal phase transition property. The PPCs are composed of three moieties (i.e., a thermoresponsive polymer backbone, a grafted peptide, and a signal-molecule label). The bioenvironment-associated phase transition behavior of PPCs are carefully studied by consideration of various crucial parameters such as chain length, hydrophilicity, ratio of grafted peptides, and concentration. Intriguingly, under the specific intracellular stimulus, the PPCs are tailored and simultaneously form nanoaggregates exhibiting long-term retention effect, which enables specific identification and quantification of endogenous factors. This general approach is expected for high-performance in situ sensing and dynamic monitoring of disease progression in living subjects.