Review
Pharmacology & Pharmacy
Macarena Sanchez-Navarro, Ernest Giralt
Summary: The blood-brain barrier is important for limiting drug delivery to the brain, but it also plays a crucial role in nutrient entrance. Peptide shuttles offer a promising strategy for increasing drug transport across the blood-brain barrier by utilizing its natural transport mechanisms. In recent years, the field of peptide shuttles has significantly evolved, with various classifications and sources being explored.
Article
Multidisciplinary Sciences
Takahiro Morito, Ryuichi Harada, Ren Iwata, Yiqing Du, Nobuyuki Okamura, Yukitsuka Kudo, Kazuhiko Yanai
Summary: Brain PET imaging using radiolabelled proteins is a promising approach for visualizing molecular targets in the brain, but faces challenges in pharmacokinetics and labelling methods. This study demonstrates the successful synthesis of a BBB-permeable affibody molecule radiolabelled with a unique fluorine-18 labelling method. The results suggest that small brain shuttle peptide-fused fluorine-18 labelled protein binders may have potential applications in brain molecular imaging.
SCIENTIFIC REPORTS
(2021)
Review
Nanoscience & Nanotechnology
Xue Zhou, Quentin R. Smith, Xinli Liu
Summary: Approximately one in six people worldwide suffer from central nervous system disorders, necessitating effective strategies to improve success rates in CNS drug discovery and development. The presence of the blood-brain barrier (BBB) poses a major obstacle to CNS drug development, but brain-penetrating peptide shuttles and PDCs have shown promise in overcoming this barrier and delivering drug molecules to the brain.
WILEY INTERDISCIPLINARY REVIEWS-NANOMEDICINE AND NANOBIOTECHNOLOGY
(2021)
Article
Pharmacology & Pharmacy
Yu-Chen Lo, Wen-Jen Lin
Summary: The study utilized a peptide-conjugated nano-delivery system to enhance penetration into tumor cells by overcoming the blood brain barrier. NPs conjugated with T7 peptide showed higher accumulation in the brain and lower biodistribution in nontarget tissues. The benefit of T7 peptide as a targeting ligand for NPs across the BBB was elucidated in this study.
Article
Chemistry, Multidisciplinary
Jeong-Won Choi, Minwook Seo, Kyunghwan Kim, A-Ru Kim, Hakmin Lee, Hyung-Seok Kim, Chun Gwon Park, Seung Woo Cho, Joo H. Kang, Jinmyoung Joo, Tae-Eun Park
Summary: By using a human microphysiological system (MPS)-based SELEX method, a human BBB shuttle aptamer (hBS) with high efficiency in crossing the blood-brain barrier was successfully screened. The hBS demonstrated enhanced uptake efficiency in brain microvascular endothelial cells and brain cells, and showed high specificity and accumulation in the brain.
Article
Pharmacology & Pharmacy
Asim Najmi, Shenggang Wang, Yue Huang, Teresa Seefeldt, Yahya Alqahtani, Xiangming Guan
Summary: The blood-brain barrier is a major challenge for most brain diseases treatment, and GSH transporter-mediated brain targeting molecule COXP has shown promising results in enhancing drug delivery to the brain.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2021)
Review
Pharmacology & Pharmacy
Xihui Gao, Jinliang Xu, Tingting Yao, Xiaoxiao Liu, Hanchang Zhang, Changyou Zhan
Summary: The blood-brain barrier (BBB) serves as a crucial physiological barrier that restricts the exchange of substances between blood and brain tissues. Peptide decorated nanocarriers have shown promise in overcoming the BBB for diagnosis and therapy of brain diseases. However, challenges related to stability, safety, and immunocompatibility need to be addressed for their clinical translation.
ADVANCED DRUG DELIVERY REVIEWS
(2022)
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.”
Article
Biochemistry & Molecular Biology
Othman Al Musaimi, Sophie Morse, Lucia Lombardi, Simona Serban, Alessandra Basso, Daryl R. Williams
Summary: Successful synthesis of the TD2.2 peptide, a blood-brain barrier shuttle, was achieved using solid-phase synthesis. This study highlights the importance of selecting the right peptide fragments for the successful synthesis of challenging peptides.
JOURNAL OF PEPTIDE SCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Radomir Juza, Kristyna Stefkova, Wim Dehaen, Alena Randakova, Tomas Petrasek, Iveta Vojtechova, Tereza Kobrlova, Lenka Pulkrabkova, Lubica Muckova, Marko Mecava, Lukas Prchal, Eva Mezeiova, Kamil Musilek, Ondrej Soukup, Jan Korabecny
Summary: In this pilot study, a series of new 3,4-dihydroquinolin-2(1H)-one derivatives were synthesized and evaluated as potential dopamine receptor D-2 (D2R) modulators. Compound 5e showed the highest D2R affinity among the synthesized compounds, with low cytotoxicity and high blood-brain barrier penetration probability. However, molecular modelling simulation revealed a different binding mode of 5e compared to USC-D301, possibly explaining the reduced affinity of 5e towards D2R.
Article
Chemistry, Multidisciplinary
Liron L. Israel, Anna Galstyan, Alysia Cox, Ekaterina S. Shatalova, Tao Sun, Mohammad-Harun Rashid, Zachary Grodzinski, Antonella Chiechi, Dieu-Trang Fuchs, Rameshwar Patil, Maya Koronyo-Hamaoui, Keith L. Black, Julia Y. Ljubimova, Eggehard Holler
Summary: The ability to cross the blood-brain barrier is crucial for targeted therapy of the central nervous system. In this study, six peptide vectors were used to enhance the permeation of the blood-brain barrier. These vectors exhibited specificity for different receptors and showed varying efficacies in different models. This research provides valuable insights into the role of nanoconjugates in treating central nervous system diseases.
Article
Engineering, Biomedical
Raleigh M. Linville, Alexander Komin, Xiaoyan Lan, Jackson G. DeStefano, Chengyan Chu, Guanshu Liu, Piotr Walczak, Kalina Hristova, Peter C. Searson
Summary: Melittin, a membrane active peptide found in bee venom, enables transient blood-brain barrier opening for delivery of therapeutics into the brain. Studies on endothelial and neuronal viability identified the effective concentration range for BBB opening, and a tissue-engineered model was used to optimize dosing and understand the mechanism. Melittin and other membrane active variants increase paracellular permeability temporarily by disrupting cell-cell junctions.
Article
Chemistry, Physical
Avneet Kour, Himanshu Sekhar Panda, Imocha Rajkumar Singh, Ashwani Kumar, Jiban Jyoti Panda
Summary: Nanotherapeutics are gaining popularity for their unique properties compared to macro materials. Metal nanoparticles (MNPs) have emerged as important due to their distinct physicochemical and biological characteristics. Peptides have various important functions in the human body and have been approved as pharmaceuticals, with clinical trials underway. Combining MNPs with peptides has potential for successful targeting, diagnosis, and therapy of neurological pathologies.
ADVANCES IN COLLOID AND INTERFACE SCIENCE
(2023)
Article
Biotechnology & Applied Microbiology
Ni Zhang, Fei Pan, Lili Pan, Wei Diao, Feijing Su, Rui Huang, Bo Yang, Yunchun Li, Zhongzhi Qi, Wenjie Zhang, Xiaoai Wu
Summary: Fibroblast activation protein (FAP) is a potential target for tumor diagnosis and treatment. This study reports the synthesis, labeling, and evaluation of a potential FAP-targeted PET tracer with blood-brain barrier-permeability.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Yi-Hui Wang, Xiao-Hui Gao, Xuan Li, Yu-Jie Ding, Qing Shi, Zhi-Yu Yang, Dian Peng, Hao-Ran Liu
Summary: A series of derivatives and analogs of daidzein were synthesized to investigate cholinesterase inhibition and blood-brain barrier permeability. The results showed that compounds containing a tertiary amine group exhibited moderate cholinesterase inhibition, while those without the tertiary amine group had no bioactivity. Compound 15a showed the best inhibitory activity with higher selectivity for AChE over BuChE.
CHEMICAL BIOLOGY & DRUG DESIGN
(2023)
Article
Chemistry, Multidisciplinary
Chenguang Lou, Josephine Tuborg Boesen, Niels Johan Christensen, Kasper K. Sorensen, Peter W. Thulstrup, Martin Nors Pedersen, Ernest Giralt, Knud J. Jensen, Jesper Wengel
CHEMISTRY-A EUROPEAN JOURNAL
(2020)
Article
Chemistry, Medicinal
Yamir Islam, Aneesa Khalid, Stefano Pluchino, Muttuswamy Sivakumaran, Meritxell Teixido, Andrew Leach, Amos A. Fatokun, James Downing, Christopher Coxon, Touraj Ehtezazi
JOURNAL OF PHARMACEUTICAL SCIENCES
(2020)
Article
Chemistry, Multidisciplinary
Davia Prischich, Alexandre M. J. Gomila, Santiago Milla-Navarro, Gemma Sanguesa, Rebeca Diez-Alarcia, Beatrice Preda, Carlo Matera, Montserrat Batlle, Laura Ramirez, Ernest Giralt, Jordi Hernando, Eduard Guasch, J. Javier Meana, Pedro de la Villa, Pau Gorostiza
Summary: The paper introduces a first generation of photochromic ligands that can modulate physiological processes by manipulating adrenergic neurotransmission, demonstrating their control effects in zebrafish and mice.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Physical
Alexandra Bukchin, Macarena Sanchez-Navarro, Adam Carrera, Meritxell Teixido, Angel M. Carcaboso, Ernest Giralt, Alejandro Sosnik
CHEMISTRY OF MATERIALS
(2020)
Article
Chemistry, Multidisciplinary
Josep Garcia, J. Marcos Fernandez-Pradas, Anna Llado, Pere Serra, Dobryna Zalvidea, Marcelo J. Kogan, Ernest Giralt, Macarena Sanchez-Navarro
Summary: By utilizing the unique photothermal properties of gold nanorods, combined with modifications of cell-penetrating peptide and nuclear targeting on proteins and AuNRs, and achieving spatiotemporal control of protein release within the safe biological window through near-infrared laser irradiation, cytosolic protein delivery has been successfully triggered.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Chemistry, Medicinal
Yamir Islam, Parinaz Ehtezazi, Andrew Cashmore, Elena Marinsalda, Andrew G. Leach, Christopher R. Coxon, Amos A. Fatokun, Darren W. Sexton, Iftikhar Khan, Georgios Zouganelis, James Downing, Stefano Pluchino, Muttuswamy Sivakumaran, Meritxell Teixido, Touraj Ehtezazi
Summary: The study investigated whether including MMP-9-sensitive sequences in brain-targeting nanoparticles could enhance BBB penetration during elevated MMP-9 levels, leading to increased transport across the BBB model when MMP-9 levels were elevated and the brain-targeting ligand was responsive to MMP-9.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2021)
Review
Pharmacology & Pharmacy
M. Masmudi-Martin, L. Zhu, M. Sanchez-Navarro, N. Priego, M. Casanova-Acebes, V. Ruiz-Rodado, E. Giralt, M. Valiente
Summary: Brain metastasis is a unique entity in oncology with specific biological characteristics and different pharmacological approaches. Despite pre-clinical evidence demonstrating vulnerabilities, many clinical trials have excluded patients with brain metastasis. Emerging trends and unsolved issues will shape the study of experimental brain metastasis in the future.
ADVANCED DRUG DELIVERY REVIEWS
(2021)
Article
Microbiology
Rafael Ayerbe-Algaba, Nuria Bayo, Ester Verdu, Raquel Parra-Millan, Jesus Seco, Meritxell Teixido, Jeronimo Pachon, Ernest Giralt, Younes Smani
Summary: In this study, ten AOA-2 derivatives were synthesized and evaluated for their effects against Gram-negative bacilli infections. Among them, RW01 and RW06 showed promising potential in improving the inhibitory effect of AOA-2, specifically against Pseudomonas aeruginosa and Escherichia coli by reducing bacterial adherence to host cells while slightly improving the viability of infected cells. Additionally, RW01 and RW06 also potentiated the activity of colistin against Acinetobacter baumannii strain, highlighting their potential as effective antimicrobial agents.
FRONTIERS IN MICROBIOLOGY
(2021)
Review
Chemistry, Multidisciplinary
Yamir Islam, Andrew G. Leach, Jayden Smith, Stefano Pluchino, Christopher R. Coxon, Muttuswamy Sivakumaran, James Downing, Amos A. Fatokun, Meritxell Teixido, Touraj Ehtezazi
Summary: The prevalence of neurological/neurodegenerative diseases, such as Alzheimer's disease, is increasing due to an aging population, posing challenges for treatment as therapeutic agents struggle to reach the brain. Brain physiology changes during diseases and aging, potentially increasing blood-brain barrier permeability, making drug delivery to the diseased brain even more complex. New approaches using nanoparticles or magnetic resonance imaging guided systems have been discussed for delivering therapeutic agents to the brain, while also considering complement activation, toxicity, and immunogenicity of brain targeting nanoparticles.
Article
Chemistry, Medicinal
Jenniffer Linares, Monica Varese, Anna Sallent-Aragay, Ana Mendez, Sergio Palomo-Ponce, Mar Iglesias, Eduard Batlle, Jorge Pisonero, Clara Montagut, Ernest Giralt, Daniele Lo Re, Alexandre Calon
Summary: We report the synthesis of a novel Pt(IV) cell-penetrating peptide conjugate, C-POC, with reduced impact on nonmalignant cells. In vitro and in vivo evaluation showed that C-POC maintains robust anticancer efficacy while reducing accumulation in healthy organs and adverse toxicity compared to standard Pt-based therapy. Our findings highlight the importance of considering the off-target impact of anticancer treatment on normal cells for improved drug development and patient care.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Salvador Guardiola, Monica Varese, Xavier Roig, Macarena Sanchez-Navarro, Jesus Garcia, Ernest Giralt
Summary: This study presents a method for designing heterochiral cyclic peptides that bind to a specific protein surface, as well as the development and biophysical evaluation of two new PD-1 inhibitors.
Article
Nanoscience & Nanotechnology
Alexandra Bukchin, Macarena Sanchez-Navarro, Adam Carrera, Claudia Resa-Pares, Helena Castillo-Ecija, Leire Balaguer-Lluna, Meritxell Teixido, Nagore G. Olaciregui, Ernest Giralt, Angel M. Carcaboso, Alejandro Sosnik
Summary: The study developed modified drug-loaded nanoparticles that can enhance transport across the blood-brain barrier and display anticancer activity in DIPG cells. These nanoparticles are mainly internalized by DIPG cells through clathrin-mediated endocytosis and show strong anticancer efficacy in vivo by killing a substantial amount of DIPG cells.
ACS APPLIED NANO MATERIALS
(2021)
Article
Materials Science, Biomaterials
Francisco Morales-Zavala, Pedro Jara-Guajardo, David Chamorro, Ana L. Riveros, America Chandia-Cristi, Nicole Salgado, Paola Pismante, Ernest Giralt, Macarena Sanchez-Navarro, Eyleen Araya, Rodrigo Vasquez, Gerardo Acosta, Fernando Albericio, Alejandra R. Alvarez, Marcelo J. Kogan
Summary: In this study, a neurotheranostic nanosystem based on gold nanorods was developed for the treatment of Alzheimer's disease. Functionalized gold nanorods were able to detect differences between wild type and AD mice, and showed promising therapeutic effects in reducing amyloid load and inflammatory markers in the brain after recurrent treatment.
BIOMATERIALS SCIENCE
(2021)
