Pre-targeted delivery of a tetrazinylated albumin–zinc(ii) porphyrin complex for tumor photodynamic therapy

Abstract

We present ZnPPA@Tz–BSA, a complex of tetrazine (Tz)-modified bovine serum albumin (Tz–BSA) and zinc porphyrin (ZnPPA), designed as a tumor-pretargeting photosensitizer. ZnPPA@Tz–BSA shows enhanced water solubility and improved reactive oxygen species (ROS) generation compared to ZnPPA alone. We demonstrate that ZnPPA@Tz–BSA can efficiently work with P-TCO through a sequential “two-step” process involving enzymatic self-immobilization labeling followed by a bioorthogonal reaction process. This strategy enables effective tumor-specific enrichment of ZnPPA@Tz–BSA, facilitating pre-targeted photodynamic therapy (PDT) of tumors in vivo.