SynB1-ELP-NBD

SynB1-ELP-NBD is a macromolecular drug conjugate designed for the thermally targeted delivery of a potent chemotherapeutic agent. It is composed of three functional modules: SynB1, a cell-penetrating peptide (CPP) that facilitates translocation across the cell membrane; an elastin-like polypeptide (ELP) scaffold that undergoes a phase transition and aggregates in response to local hyperthermia (40-42 °C); and N-butyldiacetate doxorubicin (NBD), an acid-sensitive derivative of doxorubicin reported to be three to four orders of magnitude more potent than its parent compound. This delivery system is designed to accumulate specifically within heated tumor regions, where the ELP component aggregates to enhance local concentration, followed by SynB1-mediated cellular uptake and acid-sensitive release of the cytotoxic NBD payload. Preclinical studies in pancreatic cancer models have demonstrated that SynB1-ELP-NBD induces apoptosis, cell cycle arrest, and reactive oxygen species generation, while exhibiting a significantly higher maximum tolerated dose compared to free NBD.