Review
Engineering, Biomedical
A. Zaghmi, J. Drouin-Ouellet, D. Brambilla, M. A. Gauthier
Summary: The presence of impermeable blood-brain barriers restricts access of protein therapeutics to the brain, making treating brain disorders a great challenge. Exploring new approaches to deliver proteins to the brain by circumventing physiological barriers is of great interest and importance.
Review
Pharmacology & Pharmacy
Jeehye Maeng, Kyunglim Lee
Summary: The intranasal route is a promising strategy for delivering drugs into the systemic circulation, as it avoids first-pass metabolism in the liver. Cell-penetrating peptides (CPPs) have been extensively researched as a carrier for intranasal delivery of peptides, improving the efficiency of transepithelial translocation of macromolecules.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Cell Biology
Katharina Stillger, Ines Neundorf
Summary: Personal medicine aims to tailor diagnostics and treatments, especially in targeting intracellular sites of action. Peptides are being explored as delivery vehicles that can overcome the cell membrane and achieve the final intracellular destination. These tools allow modulation of a drug's pharmacological properties without compromising its biological activity, making them valuable for targeting protein-protein interactions (PPIs), a growing therapeutic focus. This review provides an update on recent advances in cell-permeable peptides targeting subcellular destinations, including chimeric peptide probes and peptides with inherent cell-permeability that are utilized in PPI targeting.
CELLULAR SIGNALLING
(2023)
Article
Chemistry, Multidisciplinary
Nuphar Veiga, Yael Diesendruck, Dan Peer
Summary: Designing a therapeutic modality with specific delivery to certain organs, tissues, or cell types is essential for efficient treatment and minimizing off-target side effects. Nanoparticles loaded with various drugs have emerged as a promising approach to achieve this goal. However, successful targeted delivery requires overcoming multiple biological barriers, such as systemic distribution, tissue penetration, and intracellular trafficking. Recent advances in understanding these barriers and functionalizing nanoparticles with targeting moieties have shown tremendous progress. Implementing new approaches like multi-functionalized nanocarriers and machine learning models can further enhance the design of safe and cell-specific nanoparticle delivery systems. This review critically examines the current progress in the field and proposes novel strategies to improve cell-specific delivery of therapeutic payloads.
JOURNAL OF CONTROLLED RELEASE
(2023)
Article
Pharmacology & Pharmacy
Jeehye Maeng, Kyunglim Lee
Summary: This article summarizes our current understanding of TCTP-PTD and its use as a vehicle for the transduction of drugs and other molecules.
Article
Chemistry, Medicinal
Chunlei Wu, Zhehong Cheng, Danyi Lu, Ke Liu, Yulian Cheng, Pengxin Wang, Yimin Zhou, Meiqing Li, Ximing Shao, Hongchang Li, Wu Su, Lijing Fang
Summary: Researchers discovered a simplified analogue of Coibamide A and designed two novel peptide-drug conjugates, with one showing better drug release in vitro and significant tumor growth suppression in mice-bearing human tumor xenografts, indicating great potential in cancer drug discovery.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Chemistry, Multidisciplinary
Junqi Wu, Jugal Kishore Sahoo, Yamin Li, Qiaobing L. Xu, David Kaplan
Summary: Peptide- and protein-based therapeutics play a crucial role in treating various diseases, but their stability and delivery remain challenging. This review discusses the properties and challenges of these drugs, as well as delivery strategies using synthetic polymers and silk protein-based materials.
JOURNAL OF CONTROLLED RELEASE
(2022)
Article
Pharmacology & Pharmacy
Mo'ath Yousef, Ildiko Szabo, Jozsef Muranyi, Francoise Illien, Dora Soltesz, Csaba Bato, Gabriella Toth, Gyula Batta, Peter Nagy, Sandrine Sagan, Zoltan Banoczi
Summary: This study demonstrates the preparation and investigation of efficient cell-penetrating peptides (CPPs) and explores the possibility of using unnatural aromatic amino acids to mimic the properties of tryptophan. These highly active CPPs have been successful in delivering antitumor drugs into specific cell lines.
Article
Multidisciplinary Sciences
Komal Attri, Bhupendra Chudasama, Roop L. Mahajan, Diptiman Choudhury
Summary: In this study, the potential of lactoferrin-iron oxide nanoparticles (LF-IONPs) as a treatment modality for gastric cancer was investigated. The study confirms the formation of LF-IONPs with a spherical shape and an average size of 5+/-2 nm, embedded within the protein matrix. Hyperthermia studies showed that LF-IONPs can generate a sufficient rise in temperature at a low frequency, making them suitable for gastric cancer treatment. Furthermore, LF-IONPs exhibited anti-cancer activity and inhibitory effect on cell migration, suggesting their potential in targeted hyperthermia treatment of gastric cancer.
SCIENTIFIC REPORTS
(2023)
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, Multidisciplinary
Ruo-Chen Guo, Xue-Hao Zhang, Peng-Sheng Fan, Ben-Li Song, Zhi-Xiang Li, Zhong-Yu Duan, Zeng-Ying Qiao, Hao Wang
Summary: A novel in vivo self-assembly strategy is developed to induce phase separation of cell membrane, improving the internalization of therapeutic peptides and enhancing drug delivery efficacy, particularly in cancer therapy.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
William J. McDaid, Nikolai Lissin, Ellen Pollheimer, Michelle Greene, Adam Leach, Peter Smyth, Giovanna Bossi, Daniel Longley, David K. Cole, Christopher J. Scott
Summary: In this study, docetaxel-loaded polymeric nanoparticles were successfully conjugated with recombinant high affinity T cell receptors (TCRs) to target breast cancer cells. This approach enabled enhanced delivery of docetaxel and induced cell death through targeting tumour-specific peptide-HLA complexes. Overall, the study demonstrates the potential of using TCR-conjugated nanoparticles to target tumour-restricted peptide-HLA epitopes as a novel treatment strategy for delivering therapeutic drugs specifically to cancer cells.
Review
Pharmacology & Pharmacy
Ildiko Szabo, Mo'ath Yousef, Dora Soltesz, Csaba Bato, Gabor Mezo, Zoltan Banoczi
Summary: Cell-penetrating peptides (CPPs) are a diverse group of molecules with promising potential for transporting compounds into cells, but face challenges such as non-specific internalization and rapid elimination from the body. Despite growing understanding of the mechanisms involved, predicting and designing the cell-penetrating properties of CPPs remains a complex task. Efforts are being made to modify well-known CPPs in order to overcome their limitations and enhance their internalization capabilities and penetration mechanisms.
Review
Pharmacology & Pharmacy
Nicklas Osterlund, Sebastian K. T. S. Warmlander, Astrid Graslund
Summary: Cell-penetrating peptides (CPPs) derived from a prion protein (PrP) have exhibited disease-modifying properties against prion proteins and the amyloid-beta (A beta) peptide in Alzheimer's disease. These CPPs can interact with PrP/A beta and redirect their aggregation pathways, resulting in reduced cell-toxicity.
Review
Pharmacology & Pharmacy
Matilde Duran-Lobato, Ana Maria Lopez-Estevez, Ana Sara Cordeiro, Tamara G. Dacoba, Jose Crecente-Campo, Dolores Torres, Maria Jose Alonso
Summary: This review examines the historical progress in the field of protein/peptide delivery and discusses emerging technologies. It focuses on potential technologies for transmucosal systemic delivery of protein/peptide drugs, as well as new vaccination strategies for antigens and formulations of biological drugs in oncology, particularly monoclonal antibodies. Additionally, it discusses the key challenges and prospective advances in the field.
ADVANCED DRUG DELIVERY REVIEWS
(2021)
Article
Multidisciplinary Sciences
Kazutami Sakamoto, Taku Morishita, Kenichi Aburai, Daisuke Ito, Tomohiro Imura, Kenichi Sakai, Masahiko Abe, Ikuhiko Nakase, Shiroh Futaki, Hideki Sakai
Summary: CPP is a promising drug delivery vector that can penetrate biomembranes to achieve cytolysis of cells by altering the physical properties of the membrane. Studies have demonstrated the control of cytolysis of CPP by manipulating the curvature of the membrane through osmotic pressure modulation, providing insight into the mechanism behind CPP's cell-penetrating ability.
SCIENTIFIC REPORTS
(2021)
Article
Engineering, Chemical
Mizuki Kitamatsu, Ayaka Nakamura-Tachibana, Yoshimichi Ishikawa, Hiroyuki Michiue
Summary: This study successfully improved the water solubility of the conjugate BSH-3R using cyclodextrin and other methods, which could potentially enhance its application as a boron agent in boron neutron capture therapy.
Article
Biochemistry & Molecular Biology
Mizuki Kitamatsu, Hiroki Yuasa, Takashi Ohtsuki, Hiroyuki Michiue
Summary: A heterodimeric leucine zipper was used to connect protein cargos to a cell-penetrating peptide carrier, facilitating efficient delivery of bioactive proteins into cells; Formation of the LzK/LzE hybrid was confirmed through fluorescence experiments, demonstrating successful conjugation of proteins with the CPP; This method shows potential as a drug delivery system for treating various diseases.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Review
Biochemistry & Molecular Biology
Takeshi Chujo, Kazuhito Tomizawa
Summary: tRNA molecules play crucial roles in protein synthesis, and aberrations in tRNA modifications can lead to tRNA modopathies, which manifest as dysfunctions of the brain and/or kidney, mitochondrial diseases, and cancer. However, the molecular mechanisms linking aberrant tRNA modifications to diseases remain largely unknown.
Article
Chemistry, Multidisciplinary
Hiroyuki Michiue, Mizuki Kitamatsu, Asami Fukunaga, Nobushige Tsuboi, Atsushi Fujimura, Hiroaki Matsushita, Kazuyo Igawa, Tomonari Kasai, Natsuko Kondo, Hideki Matsui, Shuichi Furuya
Summary: This study explored the use of self-assembling A6K peptide nanotubes as boron carriers for tumor selective therapy, improving the limitations of BSH in intracellular transduction and non-specific drug delivery. By varying the A6K peptide and BSH mixture ratio, materials with different morphologies were produced, leading to increased intracellular boron uptake efficiency. The findings suggest that A6K peptide offers a unique and simple strategy for enhancing the effectiveness of BNCT drugs.
JOURNAL OF CONTROLLED RELEASE
(2021)
Article
Infectious Diseases
Nihad Adnan, Shahad Saif Khandker, Ahsanul Haq, Mousumi Akter Chaity, Abdul Khalek, Anawarul Quader Nazim, Taku Kaitsuka, Kazuhito Tomizawa, Masayasu Mie, Eiry Kobatake, Sohel Ahmed, Nor Azlina A. Ali, Mohib Ullah Khondoker, Mainul Haque, Mohd Raeed Jamiruddin
Summary: This study investigated the correlation of Ct value, storage temperature, and conditions with SARS-CoV-2 diagnosis using a newly developed ELISA system. Results showed that the ELISA system had highest sensitivity for samples with Ct <= 30 and stored at -80 degrees C, with specificity ranging between 98.3% and 100%. Early infection phase diagnosis and lower temperature preservation of samples are crucial for rapid antigen ELISA tests.
EXPERT REVIEW OF ANTI-INFECTIVE THERAPY
(2022)
Article
Biochemistry & Molecular Biology
Hiroyuki Fukuda, Takeshi Chujo, Fan-Yan Wei, Sheng-Lan Shi, Mayumi Hirayama, Taku Kaitsuka, Takahiro Yamamoto, Hiroyuki Oshiumi, Kazuhito Tomizawa
Summary: The study demonstrated the essential role of tRNA m(1) A58 modification in both early and late steps of HIV-1 replication, as well as the necessity of TRMT6 for efficient 5-methylation of U54 in tRNA(3)(Lys). This highlights the fundamental importance of tRNA modifications in the cellular network and underscored its significance in retroviral infection.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Oncology
Daisuke Konishi, Yuzo Umeda, Kazuhiro Yoshida, Kunitoshi Shigeyasu, Shuya Yano, Tomohiro Toji, Sho Takeda, Ryuichi Yoshida, Kazuya Yasui, Tomokazu Fuji, Kazuyuki Matsumoto, Hiroyuki Kishimoto, Hiroyuki Michiue, Fuminori Teraishi, Hironari Kato, Hiroshi Tazawa, Hiroyuki Yanai, Takahito Yagi, Ajay Goel, Toshiyoshi Fujiwara
Summary: Our study identified that CD8(+)/FoxP3(+) tumor-infiltrating lymphocytes (TILs), TIM-3, and HLA-A are highly immunogenic in intrahepatic cholangiocarcinoma (ICC). We found that intratumoral FoxP3(+) TILs correlated with CD8(+) TILs and that a high FoxP3(+)/CD8(+) ratio (FCR) was associated with poor survival in ICC. Furthermore, the FCR was higher in lymph nodes with metastasis compared to those without metastasis in ICC.
BRITISH JOURNAL OF CANCER
(2022)
Article
Multidisciplinary Sciences
Yasuhiro Komatsu, Kunitoshi Shigeyasu, Shuya Yano, Sho Takeda, Kazutaka Takahashi, Nanako Hata, Hibiki Umeda, Kazuhiro Yoshida, Yoshiko Mori, Kazuya Yasui, Ryuichi Yoshida, Yoshitaka Kondo, Hiroyuki Kishimoto, Fuminori Teraishi, Yuzo Umeda, Shunsuke Kagawa, Hiroyuki Michiue, Hiroshi Tazawa, Ajay Goel, Toshiyoshi Fujiwara
Summary: This study investigates the use of RNA editing to generate neoantigens and improve the response rates to immune checkpoint inhibitors in microsatellite stable colorectal cancers. Chemoradiation therapy is shown to upregulate the RNA editing enzyme ADAR1 and enhance RNA editing levels. The findings suggest that chemoradiation therapy can promote proteomic diversity and improve treatment outcomes.
SCIENTIFIC REPORTS
(2022)
Article
Multidisciplinary Sciences
Yasuhiko Hattori, Kazuhiko Kurozumi, Yoshihiro Otani, Atsuhito Uneda, Nobushige Tsuboi, Keigo Makino, Shuichiro Hirano, Kentaro Fujii, Yusuke Tomita, Tetsuo Oka, Yuji Matsumoto, Yosuke Shimazu, Hiroyuki Michiue, Hiromi Kumon, Isao Date
Summary: Combination therapy of Ad-SGE-REIC and bevacizumab exerts anti-glioma effects by suppressing angiogenesis and invasion, leading to extended overall survival.
Article
Engineering, Chemical
Mizuki Kitamatsu, Ken Inoue, Naoki Yamagata, Hiroyuki Michiue
Summary: This study assessed the reactivity between chloroacetyl-modified tripeptides with different amino acid residues and mercaptoundecahydrododecaborate. The results showed that the reactivity varied with the type and number of amino acid residues as well as the length of the alkyl linker. The electrostatic attraction between positively charged amino acid residues and negatively charged mercaptoundecahydrododecaborate was found to play a key role in the accelerated reaction.
Article
Gastroenterology & Hepatology
Kazutaka Takahashi, Kunitoshi Shigeyasu, Yoshitaka Kondo, Kazuyoshi Gotoh, Shuya Yano, Yuzo Umeda, Toshihiro Inokuchi, Caiming Xu, Kazuhiro Yoshida, Hibiki Umeda, Toshiaki Takahashi, Sho Takeda, Ryuichi Yoshida, Fuminori Teraishi, Hiroyuki Kishimoto, Yoshiko Mori, Kazuhiro Noma, Yoshinaga Okugawa, Sakiko Hiraoka, Hiroyuki Michiue, Hiroshi Tazawa, Osamu Matsushita, Ajay Goel, Toshiyoshi Fujiwara
Summary: Ulcerative colitis (UC) can lead to colitis-associated colorectal neoplasm (CAN), and ADAR1 may be involved in the development of CAN in UC. Assessing ADAR1 expression in the rectum of MES0 UC patients can evaluate the risk of CAN and reduce the physical burden on patients. RNA editing may be involved in UC carcinogenesis and can be used for the prevention and treatment of CAN in UC.
JOURNAL OF CROHNS & COLITIS
(2023)
Article
Multidisciplinary Sciences
Nanako Hata, Kunitoshi Shigeyasu, Yuzo Umeda, Shuya Yano, Sho Takeda, Kazuhiro Yoshida, Tomokazu Fuji, Ryuichi Yoshida, Kazuya Yasui, Hibiki Umeda, Toshiaki Takahashi, Yoshitaka Kondo, Hiroyuki Kishimoto, Yoshiko Mori, Fuminori Teraishi, Hideki Yamamoto, Hiroyuki Michiue, Keiichiro Nakamura, Hiroshi Tazawa, Toshiyoshi Fujiwara
Summary: This study found that the expression level of ADAR1 was significantly elevated in liver metastatic tissue samples from patients with CRC, particularly in right-sided, synchronous, or RAS mutant-type CRC. A high ADAR1 expression was significantly correlated with remnant liver recurrence after hepatic metastasectomy, suggesting that it could be a clinically relevant predictive indicator for remnant liver recurrence.
SCIENTIFIC REPORTS
(2023)
Article
Biochemistry & Molecular Biology
Toru Miwa, Tatsuya Katsuno, Fan-Yan Wei, Kazuhito Tomizawa
Summary: Previous studies have shown that age-related hearing loss (AHL) in Cdk5rap1-knockout mice is associated with cochlear pathology. This study aimed to identify mitochondrial alterations in the cochlea of Cdk5rap1-knockout mice with AHL. The results indicate that dysfunctional mitochondria in the lateral wall, rather than the loss of hair cells and spiral ganglion neurons, contribute to the onset of AHL. The study provides valuable insights into the underlying mechanisms of AHL and the relationship between aberrant tRNA modification-induced hearing loss and mitochondrial dysfunction.
Article
Multidisciplinary Sciences
Takafumi Shigehira, Tadashi Hanafusa, Kazuyo Igawa, Tomonari Kasai, Shuichi Furuya, Hisakazu Nishimori, Yoshinobu Maeda, Hiroyuki Michiue, Atsushi Fujimura
Summary: Boron neutron capture therapy (BNCT) is a radiation therapy that selectively kills cancer cells using the boron neutron capture reaction. The delivery dose of boron B-10 for anti-tumor effects in boron drugs is approximately 15-40 ppm, but its requirement for different boron drugs with different accumulation characteristics has not been extensively investigated.
ADVANCED THEORY AND SIMULATIONS
(2023)
