# Toward Changing Glioblastoma Outcomes: Targeted drug delivery of an inhibitory biopolymer in conjunction with systemic chemotherapy > **NIH NIH R21** · UNIVERSITY OF MISSISSIPPI MED CTR · 2020 · $174,129 ## Abstract Abstract: Toward Changing Glioblastoma Outcomes: Targeted drug delivery of an inhibitory biopolymer in conjunction with systemic chemotherapy Glioblastoma (GBM), the most common and aggressive brain tumor, ranks among the least curable cancers owing to its strong tendency for intracranial dissemination, high proliferation potential, and inherent tumor resistance to radiation and chemotherapy. Current GBM treatment strategies are hampered by a further critical challenge: adverse, nonspecific treatment effects in normal tissue and the inability of potentially effective drugs to penetrate the blood brain barrier (BBB) and reach the tumor microenvironment. We have developed an externally triggered drug delivery system to selectively deliver c-Myc transcriptional pathway inhibitory peptides (CPP-ELP-H1) to GBM tumors. This carrier, based on a thermally responsive biopolymer elastin-like polypeptide (ELP), is soluble at physiological temperatures, but undergoes a phase transition and accumulates at tumor sites when exposed to an externally applied, mild (40-41°C) hyperthermia. Conjugating this ELP with a cell-penetrating peptide (CPP) facilitates transcytosis through the BBB and tumor cell entry. The system’s anti-cancer therapeutic, an H1 peptide, antagonizes c-Myc signaling and disrupts cell proliferation. Our preliminary data show that, in a rat glioma model, CPP-ELP-H1 accumulates with the application of a mild hyperthermia in these tumors, inhibits rat glioma cells, and achieves effective tumor reduction. We thus propose here to explore and extend this novel approach in a clinically relevant, primary human GBM xenograft model in mice. We will test our system’s innovative approach to GBM treatment by assessing the effectiveness of c-Myc inhibitory polypeptide delivery to and accumulation at tumor sites. In Aim 1 we will identify polypeptide tissue and tumor concentrations, assess BBB penetration, and evaluate the capacity of an external, focused hyperthermia to further increase polypeptide levels at tumor sites. Aim 2 will demonstrate whether our engineered polypeptides can be safely administered to mice at doses required for therapeutic efficacy. We will evaluate safety profiles for our biopolymer delivery construct, conjugated with H1, when applied (1) in isolation and (2) in combination with temozolomide and radiation therapy. In Aim 3 we seek to significantly improve tumor cell responsiveness to the currently approved radiation and systemic temozolomide therapy, counter temozolomide resistant tumor xenografts, and increase GBM treatment effectiveness by applying this ‘standard-of-care’ therapy in combination with our delivery system’s GBM-targeted c-Myc transcription inhibitory peptide so as to advance our understanding of and eventual clinical armamentarium against GBM. Our goal is to contribute an effective, function-sparing therapy for patients with GBM. The proposed studies will show whether this innovative, much less toxic, targeted techn... ## Key facts - **NIH application ID:** 9961514 - **Project number:** 5R21CA229943-02 - **Recipient organization:** UNIVERSITY OF MISSISSIPPI MED CTR - **Principal Investigator:** DRAZEN RAUCHER - **Activity code:** R21 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2020 - **Award amount:** $174,129 - **Award type:** 5 - **Project period:** 2019-07-01 → 2022-06-30 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/9961514 ## Citation > US National Institutes of Health, RePORTER application 9961514, Toward Changing Glioblastoma Outcomes: Targeted drug delivery of an inhibitory biopolymer in conjunction with systemic chemotherapy (5R21CA229943-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9961514. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*