SynB1-ELP2-Dox3

SynB1-ELP2-Dox3 is a thermally insensitive macromolecular biopolymer-drug conjugate consisting of the cell-penetrating peptide SynB1, a thermally non-responsive elastin-like polypeptide (ELP2), and three molecules of doxorubicin conjugated via a pH-sensitive (6-maleimidocaproyl) hydrazone linker. It was developed by the University of Mississippi Medical Center, the Tumor Biology Center in Freiburg, and Thermally Targeted Therapeutics as a control compound to evaluate the efficacy of the thermally responsive counterpart, SynB1-ELP1-Dox3. Unlike SynB1-ELP1-Dox3, which aggregates in response to mild hyperthermia (41–42°C) to target tumor tissues, SynB1-ELP2-Dox3 remains soluble at these temperatures and does not exhibit hyperthermia-enhanced anti-tumor activity. The doxorubicin payload is released in the acidic environment of endosomes and lysosomes following cellular uptake mediated by the SynB1 peptide.