Article
Multidisciplinary Sciences
Danny D. Sahtoe, Adrian Coscia, Nur Mustafaoglu, Lauren M. Miller, Daniel Olal, Ivan Vulovic, Ta-Yi Yu, Inna Goreshnik, Yu-Ru Lin, Lars Clark, Florian Busch, Lance Stewart, Vicki H. Wysocki, Donald E. Ingber, Jonathan Abraham, David Baker
Summary: The challenge of designing polar protein-protein interactions is addressed by a computational approach utilizing complementary geometrically matched beta strands. Specifically designed proteins successfully bind to the human transferrin receptor, enabling drug delivery across the blood-brain barrier. This design strategy offers a general approach for creating binders to protein targets with exposed surface beta edge strands.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Medicine, Research & Experimental
Danielle Paige Anthony, Manasa Hegde, Shreya S. Shetty, Thasneema Rafic, Srinivas Mutalik, B. S. Satish Rao
Summary: The blood-brain barrier is a complex structure composed of endothelial cells with tight junctions and regulated by various cells like astrocytes and neurons. While traditional drug delivery methods pose challenges for treating brain diseases, receptor-mediated drug delivery is considered an efficient and safe strategy that exploits the internalization of ligands by specific receptors on the blood-brain barrier.
Article
Pharmacology & Pharmacy
Ziyao Kang, Chunlan Zeng, Long Tian, Taoran Wang, Sen Yang, Qin Cheng, Jing Zhang, Qingbin Meng, Changhao Zhang, Zhao Meng
Summary: “This study designed a series of peptide-based gene delivery vectors decorated with T7 segment to enhance gene delivery efficiency by binding to transferrin receptors highly expressed on brain tumor cells. PT-02/DNA complexes showed the highest transfection efficiency in glioma cells with low cytotoxicity in normal cell lines, and it could transport DNA across the BBB model in vitro. Moreover, in vivo experiments demonstrated that PT-02/DNA could successfully deliver pIRES2-EGFP into the brain site of zebrafish. The designed peptide vectors offer a promising approach for gene therapy in glioma.”
Review
Pharmacology & Pharmacy
Eun Seo Choi, Eric Shusta
Summary: The review focuses on known and emerging RMT systems, targeting antibody properties related to BBB trafficking, and antibody validation strategies. Clinical development of known RMT targeting systems and identifying novel BBB RMT targets are important strategies for treating CNS diseases. Expanding the identification of BBB RMT systems and targeting molecule engineering will greatly contribute to the treatment of neurological diseases.
EXPERT OPINION ON DRUG DELIVERY
(2023)
Article
Chemistry, Multidisciplinary
Jingjing Wei, Di Wu, Yu Shao, Beibei Guo, Jingjing Jiang, Jian Chen, Jinping Zhang, Fenghua Meng, Zhiyuan Zhong
Summary: The use of ApoE peptide-mediated nanodelivery system enables targeted delivery of GrB and CpG ODN to malignant glioma cells, enhancing the immunotherapy response and leading to delayed tumor progression and prolonged survival time in mice.
JOURNAL OF CONTROLLED RELEASE
(2022)
Article
Multidisciplinary Sciences
Yeh-Hsing Lao, Robin Ji, Joyce K. Zhou, Kathy J. Snow, Nancy Kwon, Ethan Saville, Siyu He, Shradha Chauhan, Chun-Wei Chi, Malika S. Datta, Hairong Zhang, Chai Hoon Quek, S. Sarah Cai, Mingqiang Li, Yaned Gaitan, Lawrence Bechtel, Shih-Ying Wu, Cathleen M. Lutz, Raju Tomer, Stephen A. Murray, Alejandro Chavez, Elisa E. Konofagou, Kam W. Leong
Summary: This study demonstrates a safe and effective gene editing technique by using focused ultrasound to transiently open the blood-brain barrier for the transport of CRISPR/Cas9 machinery to the brain.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Medicine, Research & Experimental
Xiufeng Ju, Haiyan Chen, Tongtong Miao, Jiang Ni, Liang Han
Summary: Brain metastases from breast cancer are difficult to surgically remove and have limited drug treatment options due to their growth patterns and the blood-brain barrier. By assembling prodrug-loaded nanoparticles that target both the BBB and metastatic breast cancer, researchers were able to significantly extend the survival time of mice with intracranial metastatic breast cancer, suggesting a potential important direction for drug therapy against brain metastases.
MOLECULAR PHARMACEUTICS
(2021)
Review
Chemistry, Multidisciplinary
Jia Li, Meng Zheng, Olga Shimoni, William A. Banks, Ashley I. Bush, Jennifer R. Gamble, Bingyang Shi
Summary: The blood-brain barrier is a crucial neurovascular unit that prevents harmful substances from entering the brain and maintains normal neuronal function. Disruption of BBB in diseases can contribute to disease progression, while restoration of BBB integrity is a biomarker for better clinical outcomes. The BBB also plays a role in facilitating communication between neuronal and circulatory systems, showing promising results for brain-targeted drug delivery.
Review
Chemistry, Multidisciplinary
Muhammad Daniyal Ghouri, Jabran Saleem, Jiayu Ren, Jiaming Liu, Arsalan Umer, Rong Cai, Chunying Chen
Summary: Nanomaterials, with unique physico-chemical properties such as increased surface area to mass ratio and superior adsorption capacity, are sought after for research in brain delivery of therapeutic substances. Various pathways for nanomaterials to cross BBB have been investigated, including adsorptive-mediated transcytosis, inhibition of active efflux pumps, receptor-mediated transport, and cell-mediated endocytosis.
ADVANCED MATERIALS INTERFACES
(2022)
Article
Oncology
Narges Mardi, Fatemeh Salahpour-Anarjan, Mahdieh Nemati, Nasim Shahsavari Baher, Reza Rahbarghazi, Amir Zarebkohan
Summary: The complexity of neural tissue makes it challenging to treat anaplastic changes in the brain, and the blood-brain barrier (BBB) restricts the entry of therapeutic agents. Nano-based platforms, particularly exosomes (Exos), have been used to overcome the barrier properties of BBB and enable brain penetration of selective cargos. Smart delivery approaches can further enhance delivery efficiency and therapeutic outcomes. This article highlights the recent advances in the application of Exos for brain tumors.
Article
Chemistry, Medicinal
William M. Pardridge, Tom Chou
Summary: This study examines the receptor-mediated transcytosis of monoclonal antibodies targeting transferrin receptor or insulin receptor at the blood-brain barrier, using mathematical models to analyze and predict the transport process. The optimal rates of receptor association with the targeted antibodies are highlighted as crucial factors determining the efficiency of transcytosis.
Review
Pharmacology & Pharmacy
Kibeom Kim, Jungmin Lee, Myoung-Hwan Park
Summary: The blood-brain barrier is an important barrier that protects the brain and maintains homeostasis. Traditional drug delivery methods face limitations such as low diversity and efficiency. Microbubble-based drug delivery systems, which utilize ultrasound-induced physical changes, have gained attention in recent years for their ability to enhance drug delivery by disrupting the blood-brain barrier.
Review
Chemistry, Multidisciplinary
Luyao Wang, Youyuan Shi, Jingzhen Jiang, Chan Li, Hengrui Zhang, Xinhui Zhang, Tao Jiang, Liang Wang, Yinyan Wang, Lin Feng
Summary: The blood-brain barrier (BBB) poses a significant challenge for drug delivery to brain tumors. Recent research in micro- and nanotechnology has shown that nano drug-targeted delivery technologies have the potential to overcome this challenge. This review provides a detailed understanding of the BBB, summarizes recent research topics on drug delivery carriers for brain tumors, evaluates the effectiveness of targeted therapy, and discusses the challenges and future prospects of developing brain tumor drug delivery systems.
Article
Chemistry, Medicinal
William M. Pardridge
Summary: Biologic drugs are large molecule pharmaceuticals that cannot cross the blood-brain barrier. They can be re-engineered for BBB transport as IgG fusion proteins. The kinetics of BBB transport can be quantified with mathematical models.
Article
Engineering, Biomedical
Marie J. Pauwels, Junhua Xie, Adam Ceroi, Sriram Balusu, Jonas Castelein, Elien Van Wonterghem, Griet Van Imschoot, Andrew Ward, Trevelyan R. Menheniott, Oskar Gustafsson, Francis Combes, Samir El Andaloussi, Niek N. Sanders, Imre Mager, Lien Van Hoecke, Roosmarijn E. Vandenbroucke
Summary: The brain is protected by tightly regulated barriers, which impede drug delivery. Extracellular vesicles derived from choroid plexus epithelial cells have the potential to serve as drug delivery vehicles to bypass these barriers.
