Tumor microenvironment-responsive charge reversal zinc phthalocyanines based on amino acids for photodynamic therapy

•Charge reversible zinc phthalocyanines substituted with amino acids were prepared.•The isoelectric pHs and charge reversal sensitivity of AAZnPcs were regulated.•The charge of AAZnPcs can be responsive to tumor microenvironment.•Charge reversible GluZnPc and OGluZnPc showed enhanced photodynamic activities.•GluZnPc and OGluZnPc are promising photosensitizers for photodynamic therapy.

Amino acid substituted zinc phthalocyanines which are capable of reversing their charge from negative to positive in response to tumor microenvironment have been prepared by the isoelectric pHs regulation and charge reversal sensitivity enhancement. The charge reversal abilities of the prepared zinc phthalocyanines were judged by their isoelectric pHs and zeta potential values. The UV–Vis spectra, singlet oxygen generation ability, cellular uptake and in vitro anticancer ability of the prepared zinc phthalocyanines were investigated to study the influences of charge reversal on photodynamic activities. Charge reversible tetra- and octa-substituted glutamic acid ZnPcs showed enhanced singlet oxygen generation ability, cellular uptake and photocytotoxicity towards cancer cells, and were considered as promising photosensitizers for photodynamic therapy.

Graphical abstractAmino acid substituted zinc phthalocyanines which are capable of reversing their charge from negative to positive in response to tumor microenvironment have been prepared for photodynamic therapy.Figure optionsDownload full-size imageDownload as PowerPoint slide