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SynB1 ELP1-DOXO

Development stage: Preclinical
Lead developer: University of Mississippi Medical Center
Modality: Peptide-Drug Conjugates → Peptide Conjugates → Peptides, Biodegradable Polymers → Polymer-based Nanoparticles → Nanoparticles → Drug Delivery Systems
Administration: Intravenous

Overview

SynB1 ELP1-DOXO is an experimental, thermally responsive biopolymer-drug conjugate designed for targeted delivery of doxorubicin to solid tumors. The construct consists of three functional components: SynB1, a cell-penetrating peptide that enhances cellular uptake via adsorptive endocytosis; ELP1, a thermally responsive elastin-like polypeptide (ELP) that aggregates in response to mild hyperthermia (above ~38°C) to enable localized thermal targeting; and DOXO-EMCH, a (6-maleimidocaproyl) hydrazone derivative of doxorubicin linked via a pH-sensitive hydrazone bond. This pH-sensitive linker allows selective release of doxorubicin in the acidic environment of tumor endosomes and lysosomes. In preclinical models of breast cancer and glioblastoma, SynB1 ELP1-DOXO has demonstrated enhanced tumor accumulation and a significant reduction in cardiac doxorubicin accumulation, suggesting a potential to minimize cardiotoxicity compared to free doxorubicin.

Other names: SynB1-ELP1-(DOXO)3

Targets

TOP2A (DNA topoisomerase II)DNA

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