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) and the recovery of intramolecular electrostatic interaction between (Lys) and (Glu). Then (Glu) folded (Lys) 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.