A supramolecular nanocarrier for efficient cancer imaging and therapy by targeting at matriptase.

Human serum albumin (HSA), a versatile protein carrier for endogenous and exogenous compounds, is a proven macromolecule to form nanoparticles for drug delivery. To render HSA carrier specificity toward tumors, we designed a recombinant HSA protein fused with Kunitz domain 1 (KD1) of hepatocyte growth factor activator inhibitor type 1, which targets to matriptase, a type II transmembrane serine protease overexpressed on tumor cell surface. The carrier was thus named matriptase targeting carrier (MTC). In this study, we showed that MTC displayed the same inhibitory potency as the KD1 againast matriptase, demonstrating the HSA fusion did not affect the KD1 targeting potency. For tumor optical imaging and ablation, MTC was prepared as nanoparticle drug carrier by a novel method via denaturation and refolding to incorporate photosensitizer, CPZ. This matriptase targeting nanoparticles, CPZ:MTC@NPs, showed high specificity and cytotoxicity for matriptase-overexpressing cancer cells in vitro. In tumor-bearing mice, CPZ:MTC@NPs demonstrated selective accumulation and high retention in matriptase-overexpressing tumor. Under illumination, the nanoparticles significantly reduced tumor volumes (79.6%) as compared to saline control. These findings showed that this supramolecular nanocarrier, a new type of tumor targeting self-assembly nanoparticle, had potential as a highly efficient tumor targeting drug carrier for imaging and therapy.