ROS-initiated in-situ polymerization of diacetylene-containing lipidated peptide amphiphile in living cells

Recently, in-situ polymerization inside living cells has attracted much attention due to the efficient cellular internalization and elevated drug retention. However, the lack of tracking of the in-situ polymerization process and the unclear effects of polymerization on cellular functions restrict its biomedical applications. Herein, we designed a Y-shaped diacetylene-containing lipidated peptide amphiphile (Y-DLPA1) with positive charges, which underwent in-situ polymerization initiated by reactive oxygen species in the intracellular microenvironment. In comparison, zwitterionic Y-DLPA2 and negatively charged Y-DLPA3 were polymerized in aqueous solution, but cannot polymerize in the intracellular microenvironment. The polymerized Y-DLPA1 with red fluorescence provides a platform to label cells for long-term tracking studies. This polymerization reaction induced tumor cell apoptosis, increased cell viscosity and decreased cell motility, which potentially inhibited tumor metastasis and served as a novel antitumor agent. This work provides a novel strategy to track in-situ polymerization process and modulate cell biofunctions.

Automated summary

This study presents a designed peptide micelle capable of undergoing in-situ polymerization inside cells, enabling cell labeling and long-term tracking using fluorescence. The polymerization process induces tumor cell apoptosis, increases cell viscosity, and decreases cell motility, potentially inhibiting tumor metastasis.