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Tumor-targeting cell-penetrating peptide, p28, for glioblastoma imaging and therapy
Sunam Mander1, Samer A Naffouje1, Jin Gao2
1Department of Surgery, Division of Surgical Oncology, University of Illinois College of Medicine, Chicago, IL, United States.
Abstract:
Despite recent advances in cancer research, glioblastoma multiforme (GBM) remains a highly aggressive brain tumor as its treatment options are limited. The current standard treatment includes surgery followed by radiotherapy and adjuvant chemotherapy. However, surgery without image guidance is often challenging to achieve maximal safe resection as it is difficult to precisely discern the lesion to be removed from surrounding brain tissue. In addition, the efficacy of adjuvant chemotherapy is limited by poor penetration of therapeutics through the blood-brain barrier (BBB) into brain tissues, and the lack of tumor targeting. In this regard, we utilized a tumor-targeting cell-penetration peptide, p28, as a therapeutic agent to improve the efficacy of a current chemotherapeutic agent for GBM, and as a carrier for a fluorescence imaging agent for a clear identification of GBM. Here, we show that a near-infrared (NIR) imaging agent, ICG-p28 (a chemical conjugate of an FDA-approved NIR dye, indocyanine green ICG, and tumor-targeting p28 peptide) can preferentially localize tumors in multiple GBM animal models. Moreover, xenograft studies show that p28, as a therapeutic agent, can enhance the cytotoxic activity of temozolomide (TMZ), one of the few effective drugs for brain tumors. Collectively, our findings highlight the important role of the tumor-targeting peptide, which has great potential for intraoperative image-guided surgery and the development of new therapeutic strategies for GBM.
Insights
A novel peptide, p28, enhances glioblastoma (GBM) imaging and chemotherapy. ICG-p28 aids tumor visualization, while p28 boosts temozolomide efficacy for improved GBM treatment strategies.
Area of Science:
- Oncology
- Neuroscience
- Biomedical Engineering
Background:
- Glioblastoma multiforme (GBM) is an aggressive brain tumor with limited treatment options.
- Current treatments like surgery, radiotherapy, and chemotherapy face challenges including precise surgical resection and drug delivery across the blood-brain barrier (BBB).
- Lack of effective tumor targeting and poor therapeutic penetration limit treatment efficacy.
Purpose of the Study:
- To develop a tumor-targeting peptide, p28, for enhanced glioblastoma (GBM) imaging and therapy.
- To evaluate the efficacy of p28 as a carrier for a near-infrared (NIR) imaging agent (ICG-p28) for intraoperative GBM identification.
- To assess the potential of p28 to improve the efficacy of temozolomide (TMZ) chemotherapy for GBM.
Main Methods:
- Conjugation of p28 peptide with indocyanine green (ICG) to create ICG-p28 for fluorescence imaging.
- Testing ICG-p28's tumor-localizing ability in multiple GBM animal models.
- Evaluating p28's therapeutic effect in combination with temozolomide (TMZ) in xenograft studies.
Main Results:
- ICG-p28 demonstrated preferential localization to GBM tumors in various animal models.
- Xenograft studies confirmed that p28 enhances the cytotoxic activity of temozolomide (TMZ).
- The tumor-targeting peptide p28 showed significant potential in both imaging and therapeutic applications for GBM.
Conclusions:
- The tumor-targeting peptide p28 holds great promise for intraoperative image-guided surgery in GBM.
- p28 can serve as a carrier for imaging agents, improving GBM visualization.
- p28 represents a potential strategy to enhance the efficacy of existing chemotherapeutic agents like TMZ for GBM treatment.
