Pre-targeted delivery of 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 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 of tumors in vivo.