Ultra-pH-sensitive polypeptide micelles with large fluorescence off/on ratio in near infrared range

An amphiphilic copolymer of poly(oligo(ethylene glycol) methacrylate) (POEGMA) and poly(benzyl-L-aspartic acid) (PBLA) has been prepared by means of reversible addition–fragmentation chain transfer (RAFT) polymerization, ring-opening polymerization, and click reaction. After the PBLA segment was aminolyzed by the primary amine, N,N-diisopropylethylenediamine (DIEDA) and N,N-dibutylethylenediamine (DBEDA) with different ratios, amphiphilic block copolymers with various ionizable tertiary amines have been prepared, which can form stable micelles in neutral pH by self-assembly and disassembly under weak acidic conditions. After conjugation of Cy5.5/quencher to the copolymer, the as-formed micelles exhibit low fluorescence due to the Fluorescence Resonance Energy Transfer (FRET) between Cy5.5 and the quencher. However, an ultra-pH-sensitive fluorescence can be switched-on when it was in weak acidic conditions. The as-prepared nanoparticles have potential application in highly sensitive detection of the pH of tissues and cells, and can also work as a theranostic for cancer with drug delivery and imaging ability.