Thermally Targeted Delivery of a c-Myc Inhibitory Polypeptide Inhibits Tumor Progression and Extends Survival in a Rat Glioma Model
نویسندگان
چکیده
Treatment of glioblastoma is complicated by the tumors' high resistance to chemotherapy, poor penetration of drugs across the blood brain barrier, and damaging effects of chemotherapy and radiation to normal neural tissue. To overcome these limitations, a thermally responsive polypeptide was developed for targeted delivery of therapeutic peptides to brain tumors using focused hyperthermia. The peptide carrier is based on elastin-like polypeptide (ELP), which is a thermally responsive biopolymer that forms aggregates above a characteristic transition temperature. ELP was modified with cell penetrating peptides (CPPs) to enhance delivery to brain tumors and mediate uptake across the tumor cells' plasma membranes and with a peptide inhibitor of c-Myc (H1). In rats with intracerebral gliomas, brain tumor targeting of ELP following systemic administration was enhanced up to 5-fold by the use of CPPs. When the lead CPP-ELP-fused c-Myc inhibitor was combined with focused hyperthermia of the tumors, an additional 3 fold increase in tumor polypeptide levels was observed, and 80% reduction in tumor volume, delayed onset of tumor-associated neurological deficits, and at least doubled median survival time including complete regression in 80% of animals was achieved. This work demonstrates that a c-Myc inhibitory peptide can be effectively delivered to brain tumors.
منابع مشابه
Thermally Targeted Delivery of a c-Myc Inhibitory Peptide in Vivo Using Elastin-Like Polypeptide
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Glioma, as a primary tumor of central nervous system, is the main cause of death in patients with brain cancer. Therefore, development of an efficient strategy for treatment of glioma is worthy. The aim of the current study was to develop a SRL peptide-coated dendrimer as a novel dual gene delivery system for targeting the LRP receptor, an up-regulated gene in both BBB and glioma cells. To perf...
متن کاملThermally Targeted Delivery of a c-Myc Inhibitory Peptide In Vivo Using Elastin-like Polypeptide PRINCIPAL INVESTIGATOR:
Article history: The therapeutic index of cur Received 30 July 2008 Accepted 11 November 2008 Available online xxxx
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