Steric shielding protected and acidity-activated pop-up of ligand for tumor enhanced photodynamic therapy

Tumor targeted drug delivery in vivo remains a significant challenge in tumor therapy. In this article, we fabricated a steric shielding protected/tumor acidity-activated chimeric peptide for tumor targeted photodynamic therapy . This amphiphilic chimeric peptide could form spherical nanoparticles at neutrally physiological environment with the shielding of biotin molecule (tumor target ligand). When in tumor acidic microenvironment, acidity-sensitive dimethylmaleic amide was rapidly hydrolyzed, resulting in subsequent liberation of (Lys) 8 and the recovery of intramolecular electrostatic interaction between (Lys) 8 and (Glu) 8 . Then (Glu) 8 folded (Lys) 8 and biotin molecule was popped up to the surface of nanoparticles. Both in vitro and in vivo studies indicated that this steric shielding protected/tumor acidity-activated pop-up strategy demonstrated here could remarkably enhance tumor specific accumulation/internalization of chimeric peptide, improve photodynamic therapy efficacy and minimize the side effects. This strategy should not only be used for phototherapy, but also open a window to endow nanocarriers with effective tumor target ability.