Addressing BBB Heterogeneity: A New Paradigm for Drug Delivery to Brain Tumors

Overview

Journal Pharmaceutics

Publisher MDPI

Date 2020 Dec 16

PMID 33322488

Citations 21

Authors

Jessica I Griffith

Sneha Rathi

Wenqiu Zhang

Wenjuan Zhang

Lester R Drewes

Jann N Sarkaria

William F Elmquist

Affiliations

Soon will be listed here.

Abstract

Effective treatments for brain tumors remain one of the most urgent and unmet needs in modern oncology. This is due not only to the presence of the neurovascular unit/blood-brain barrier (NVU/BBB) but also to the heterogeneity of barrier alteration in the case of brain tumors, which results in what is referred to as the blood-tumor barrier (BTB). Herein, we discuss this heterogeneity, how it contributes to the failure of novel pharmaceutical treatment strategies, and why a "whole brain" approach to the treatment of brain tumors might be beneficial. We discuss various methods by which these obstacles might be overcome and assess how these strategies are progressing in the clinic. We believe that by approaching brain tumor treatment from this perspective, a new paradigm for drug delivery to brain tumors might be established.

Citing Articles

Deep learning radiomics for the prediction of epidermal growth factor receptor mutation status based on MRI in brain metastasis from lung adenocarcinoma patients.

Cao P, Jia X, Wang X, Fan L, Chen Z, Zhao Y BMC Cancer. 2025; 25(1):443.

PMID: 40075375 PMC: 11899356. DOI: 10.1186/s12885-025-13823-8.

Tuning a bioengineered hydrogel for studying astrocyte reactivity in glioblastoma.

DePalma T, Hisey C, Hughes K, Fraas D, Tawfik M, Scharenberg J Acta Biomater. 2024; 189:155-167.

PMID: 39370091 PMC: 11801334. DOI: 10.1016/j.actbio.2024.09.048.

A Review of Therapeutic Agents Given by Convection-Enhanced Delivery for Adult Glioblastoma.

Rolfe N, Dadario N, Canoll P, Bruce J Pharmaceuticals (Basel). 2024; 17(8).

PMID: 39204078 PMC: 11357193. DOI: 10.3390/ph17080973.

Blood-tumor barrier in focus - investigation of glioblastoma-induced effects on the blood-brain barrier.

Mathew-Schmitt S, Peindl M, Neundorf P, Dandekar G, Metzger M, Nickl V J Neurooncol. 2024; 170(1):67-77.

PMID: 39196480 PMC: 11446994. DOI: 10.1007/s11060-024-04760-w.

H3K27-Altered Diffuse Midline Glioma of the Brainstem: From Molecular Mechanisms to Targeted Interventions.

Nonnenbroich L, Bouchal S, Millesi E, Rechberger J, Khatua S, Daniels D Cells. 2024; 13(13.

PMID: 38994974 PMC: 11240752. DOI: 10.3390/cells13131122.

References

Kariolis M, Wells R, Getz J, Kwan W, Mahon C, Tong R . Brain delivery of therapeutic proteins using an Fc fragment blood-brain barrier transport vehicle in mice and monkeys. Sci Transl Med. 2020; 12(545). DOI: 10.1126/scitranslmed.aay1359. View

Graham-Gurysh E, Murthy A, Moore K, Hingtgen S, Bachelder E, Ainslie K . Synergistic drug combinations for a precision medicine approach to interstitial glioblastoma therapy. J Control Release. 2020; 323:282-292. PMC: 7453575. DOI: 10.1016/j.jconrel.2020.04.028. View

Sampath P, Amundson E, Wall M, Tyler B, Wani M, Alderson L . Camptothecin analogs in malignant gliomas: comparative analysis and characterization. J Neurosurg. 2003; 98(3):570-7. DOI: 10.3171/jns.2003.98.3.0570. View

Carpentier A, Canney M, Vignot A, Reina V, Beccaria K, Horodyckid C . Clinical trial of blood-brain barrier disruption by pulsed ultrasound. Sci Transl Med. 2016; 8(343):343re2. DOI: 10.1126/scitranslmed.aaf6086. View

Xu L, Huang C, Huang W, Tang W, Rait A, Yin Y . Systemic tumor-targeted gene delivery by anti-transferrin receptor scFv-immunoliposomes. Mol Cancer Ther. 2002; 1(5):337-46. View

Terasaki T, Ohtsuki S . Brain-to-blood transporters for endogenous substrates and xenobiotics at the blood-brain barrier: an overview of biology and methodology. NeuroRx. 2005; 2(1):63-72. PMC: 539321. DOI: 10.1602/neurorx.2.1.63. View

Lin C, Li R, Huang C, Wei K, Chen P . Controlled release of liposome-encapsulated temozolomide for brain tumour treatment by convection-enhanced delivery. J Drug Target. 2017; 26(4):325-332. DOI: 10.1080/1061186X.2017.1379526. View

Liu H, Hsu P, Lin C, Huang C, Chai W, Chu P . Focused Ultrasound Enhances Central Nervous System Delivery of Bevacizumab for Malignant Glioma Treatment. Radiology. 2016; 281(1):99-108. DOI: 10.1148/radiol.2016152444. View

Kreuter J . Mechanism of polymeric nanoparticle-based drug transport across the blood-brain barrier (BBB). J Microencapsul. 2012; 30(1):49-54. DOI: 10.3109/02652048.2012.692491. View

10.

Kumthekar P, Tang S, Brenner A, Kesari S, Piccioni D, Anders C . ANG1005, a Brain-Penetrating Peptide-Drug Conjugate, Shows Activity in Patients with Breast Cancer with Leptomeningeal Carcinomatosis and Recurrent Brain Metastases. Clin Cancer Res. 2020; 26(12):2789-2799. DOI: 10.1158/1078-0432.CCR-19-3258. View

11.

Garcia F, Carrion N, de la Cruz-Merino L . Long-term complete response to intrathecal trastuzumab in a patient with leptomeningeal carcinomatosis due to her2- overexpressing breast cancer: Case report. Medicine (Baltimore). 2020; 99(1):e18298. PMC: 6946348. DOI: 10.1097/MD.0000000000018298. View

12.

Ozerov S, Thomale U, Schulz M, Schaumann A, Samarin A, Kumirova E . The use of a smartphone-assisted ventricle catheter guide for Ommaya reservoir placement-experience of a retrospective bi-center study. Childs Nerv Syst. 2018; 34(5):853-859. DOI: 10.1007/s00381-017-3713-6. View

13.

Oller-Salvia B, Sanchez-Navarro M, Giralt E, Teixido M . Blood-brain barrier shuttle peptides: an emerging paradigm for brain delivery. Chem Soc Rev. 2016; 45(17):4690-707. DOI: 10.1039/c6cs00076b. View

14.

Householder K, Dharmaraj S, Sandberg D, Wechsler-Reya R, Sirianni R . Fate of nanoparticles in the central nervous system after intrathecal injection in healthy mice. Sci Rep. 2019; 9(1):12587. PMC: 6715675. DOI: 10.1038/s41598-019-49028-w. View

15.

Abbott N, Patabendige A, Dolman D, Yusof S, Begley D . Structure and function of the blood-brain barrier. Neurobiol Dis. 2009; 37(1):13-25. DOI: 10.1016/j.nbd.2009.07.030. View

16.

Lu N, Raizer J, Gabor E, Liu N, Vu J, Slamon D . Intrathecal trastuzumab: immunotherapy improves the prognosis of leptomeningeal metastases in HER-2+ breast cancer patient. J Immunother Cancer. 2015; 3:41. PMC: 4570757. DOI: 10.1186/s40425-015-0084-y. View

17.

Argaw A, Gurfein B, Zhang Y, Zameer A, John G . VEGF-mediated disruption of endothelial CLN-5 promotes blood-brain barrier breakdown. Proc Natl Acad Sci U S A. 2009; 106(6):1977-82. PMC: 2644149. DOI: 10.1073/pnas.0808698106. View

18.

Liu H, Hua M, Yang H, Huang C, Chu P, Wu J . Magnetic resonance monitoring of focused ultrasound/magnetic nanoparticle targeting delivery of therapeutic agents to the brain. Proc Natl Acad Sci U S A. 2010; 107(34):15205-10. PMC: 2930577. DOI: 10.1073/pnas.1003388107. View

19.

Vogelbaum M, Brewer C, Barnett G, Mohammadi A, Peereboom D, Ahluwalia M . First-in-human evaluation of the Cleveland Multiport Catheter for convection-enhanced delivery of topotecan in recurrent high-grade glioma: results of pilot trial 1. J Neurosurg. 2018; 130(2):476-485. DOI: 10.3171/2017.10.JNS171845. View

20.

Frazier J, Wang P, Case D, Tyler B, Pradilla G, Weingart J . Local delivery of minocycline and systemic BCNU have synergistic activity in the treatment of intracranial glioma. J Neurooncol. 2003; 64(3):203-9. DOI: 10.1023/a:1025695423097. View