Improving the enrichment of drugs or
theranostic agents within
tumors is vital to achieve effective
cancer diagnosis and
therapy with reduced dosage and damage to normal tissues. In this work, an
enzyme-mediated aggregation-induced emission fluorogen (AIEgen) intracellular polymerization strategy that can simultaneously promote the accumulation and retention of the AIEgen in the
tumor for prolonged imaging and enhanced
tumor growth inhibition is described. An AIEgen-
peptide conjugate (D2P1) and cyanobenzothiazole-
cysteine (3CBT) that can undergo rapid condensation reaction to form nanoaggregates in
tumor cells are rationally designed. Upon
tumor-specific
cathepsin protease reaction, the cleavage of
peptides induces condensate polymerization between the exposed
cysteine and
2-cyanobenzothiazole on 3CBT, triggering accumulation of D2P1 into the
tumor site, leading to fluorescence light-up. Such
enzyme-mediated polymerization of D2P1 and 3CBT alters cellular motility via disrupting actin organization and in turn inhibiting cell proliferation. In addition, due to the built-in intrinsic
photosensitization property of the AIEgen, the accumulation of D2P1 can remarkably promote the
tumor photodynamic therapy effect in vivo under light irradiation. This study thus represents the
enzyme-mediated intracellular polymerization system with high potential to improve the diagnostic and therapeutic outcomes of
tumors in vivo.