SynB1-ELP-DOXO

SynB1-ELP-DOXO is a thermally responsive macromolecular drug conjugate designed for targeted delivery of doxorubicin to solid tumors. The construct is composed of three main components: SynB1, a cell-penetrating peptide derived from the protegrin family of antimicrobial peptides (porcine leukocytes) that enhances cellular and intratumoral uptake; a thermally responsive elastin-like polypeptide (ELP) carrier that remains soluble at physiological temperature but aggregates in response to mild hyperthermia (~41-42 °C) to increase local drug concentration; and an acid-sensitive (6-maleimidocaproyl) hydrazone derivative of doxorubicin (DOXO-EMCH) conjugated to terminal cysteine residues on the ELP. Upon cellular internalization via adsorptive endocytosis, the acid-labile hydrazone linker is cleaved in the acidic environment of endosomes and lysosomes, releasing active doxorubicin. Doxorubicin then localizes to the nucleus, where it intercalates into DNA and inhibits topoisomerase II, leading to cell cycle arrest in the G2/M phase and apoptosis. SynB1-ELP-DOXO has been evaluated in preclinical models of breast cancer and glioblastoma.

Other names

SynB1-ELP1-(DOXO)3SynB1-elastin-like polypeptide-doxorubicin conjugateSynB-1-elastin-like polypeptide-doxorubicin conjugateSynB 1-elastin-like polypeptide-doxorubicin conjugate