作者: Chiocca, E. Antonio ; Ghotmi, Yarah ; Lamfers, Martine L. M. ; Dubey, Shipra ; Wolfe, Justin M. ; Fadzen, Colin M. ; Murrell, Emily ; Scott, Benjamin ; Cho, Choi‐Fong ; DiCarli, Marcelo ; Zdioruk, Mykola ; Hartrampf, Nina ; Luyt, Leonard G. ; Yang, Bo Yeun ; Wasserburg, J. Roscoe ; Kijewski, Marie F. ; Farquhar, Charlotte ; Lawler, Sean E. ; Pentelute, Bradley L. ; Wang, Shuyan ; Ligon, Keith L. ; von Spreckelsen, Niklas ; Bergmann, Sonja ; Viapiano, Mariano S. ; Bononi, Fernanda C.

AbstractGlioblastoma (GBM) is the most common and deadliest form of brain tumor and remains amongst the most difficult cancers to treat. Brevican (Bcan), a central nervous system (CNS)‐specific extracellular matrix protein, is upregulated in high‐grade glioma cells, including GBM. A Bcan isoform lacking most glycosylation, dg‐Bcan, is found only in GBM tissues. Here, dg‐Bcan is explored as a molecular target for GBM. In this study, a d‐peptide library is screened to identify a small 8‐amino acid dg‐Bcan‐Targeting Peptide (BTP) candidate, called BTP‐7 that binds dg‐Bcan with high affinity and specificity. BTP‐7 is preferentially internalized by dg‐Bcan‐expressing patient‐derived GBM cells. To demonstrate GBM targeting, BTP‐7 is radiolabeled with 18F, a radioisotope of fluorine, and increased radiotracer accumulation is found in intracranial GBM established in mice using positron emission tomography (PET) imaging. dg‐Bcan is an attractive molecular target for GBM, and BTP‐7 represents a promising lead candidate for further development into novel imaging agents and targeted therapeutics.

Cancers2区 · 医学

A Tumor-Homing Peptide Platform Enhances Drug Solubility, Improves Blood–Brain Barrier Permeability and Targets Glioblastoma

2区 · 医学

ArticleOA

作者: Zhuang, Pei ; Cho, Choi-Fong ; Farquhar, Charlotte E. ; Loas, Andrei ; Hartrampf, Nina ; Lawler, Sean E. ; Scott, Benjamin ; von Spreckelsen, Niklas ; Pentelute, Bradley L. ; Fadzen, Colin M.

Background: Glioblastoma (GBM) is the most common and deadliest malignant primary brain tumor, contributing significant morbidity and mortality among patients. As current standard-of-care demonstrates limited success, the development of new efficacious GBM therapeutics is urgently needed. Major challenges in advancing GBM chemotherapy include poor bioavailability, lack of tumor selectivity leading to undesired side effects, poor permeability across the blood–brain barrier (BBB), and extensive intratumoral heterogeneity. Methods: We have previously identified a small, soluble peptide (BTP-7) that is able to cross the BBB and target the human GBM extracellular matrix (ECM). Here, we covalently attached BTP-7 to an insoluble anti-cancer drug, camptothecin (CPT). Results: We demonstrate that conjugation of BTP-7 to CPT improves drug solubility in aqueous solution, retains drug efficacy against patient-derived GBM stem cells (GSC), enhances BBB permeability, and enables therapeutic targeting to intracranial GBM, leading to higher toxicity in GBM cells compared to normal brain tissues, and ultimately prolongs survival in mice bearing intracranial patient-derived GBM xenograft. Conclusion: BTP-7 is a new modality that opens the door to possibilities for GBM-targeted therapeutic approaches.

Journal of Microencapsulation

Dual-targeting liposomes modified with BTP-7 and pHA for combined delivery of TCPP and TMZ to enhance the anti-tumour effect in glioblastoma cells

Article

作者: Du, Jingguo ; Zhong, Yonglong ; Tang, Zijun ; Jing, Lin ; Li, Lili ; Yuan, Mingqing ; Liu, Xu

AIMTo construct a novel nano-carrier with dual ligands to achieve superior anti-tumour efficacy and lower toxic side effects.METHODSLiposomes were prepared by thin film hydration method. Ultraviolet, high performance liquid chromatography, nano-size analyser, ultrafiltration centrifugation, dialysis, transmission electron microscope, flow cytometry, Cell Counting Kit-8, confocal laser scanning microscopy, transwell, and tumorsphere assay were used to study the characterisations, cytotoxicity, and in vitro targeting of dg-Bcan targeting peptide (BTP-7)/pHA-temozolomide (TMZ)/tetra(4-carboxyphenyl)porphyrin (TCPP)-Lip.RESULTSBTP-7/pHA-TMZ/TCPP-Lip was a spheroid with a mean diameters of 143 ± 3.214 nm, a polydispersity index of 0.203 ± 0.025 and a surface charge of -22.8 ± 0.425 mV. The drug loadings (TMZ and TCPP) are 7.40 ± 0.23% and 2.05 ± 0.03% (mg/mg); and the encapsulation efficiencies are 81.43 ± 0.51% and 84.28 ± 1.64% (mg/mg). The results showed that BTP-7/pHA-TMZ/TCPP-Lip presented enhanced targeting and cytotoxicity.CONCLUSIONBTP-7/pHA-TMZ/TCPP-Lip can specifically target the tumour cells to achieve efficient drug delivery, and improve the anti-tumour efficacy and reduces the systemic toxicity.

100 项与 BTP-7 相关的药物交易

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