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CPP-ELP-Dox is a thermally sensitive drug conjugate designed for the targeted delivery of doxorubicin to glioblastoma (GBM) tumors. The construct consists of three primary components: a cell-penetrating peptide (CPP) to facilitate crossing the blood-brain barrier (BBB) and cellular uptake, an elastin-like polypeptide (ELP) that undergoes a phase transition to accumulate at tumor sites under mild hyperthermia (40-41°C), and doxorubicin (Dox) attached via an acid-sensitive 6-maleimidocaproyl hydrazone linker. This linker ensures the selective release of the cytotoxic payload within the acidic environment of lysosomes and endosomes following cellular internalization. Developed through a collaboration between the University of Mississippi Medical Center and CytRx Corporation, CPP-ELP-Dox aims to enhance the therapeutic efficacy of doxorubicin in GBM while minimizing systemic toxicity and overcoming the challenges of BBB penetration.
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