Article
Chemistry, Multidisciplinary
Yan Zhao, Haolin Jiang, Jiazhen Yu, Luyao Wang, Juanjuan Du
Summary: Currently, the clinical application of protein/peptide therapeutics is limited to the extracellular spaces, mainly due to the endosomal entrapment of internalized proteins/peptides. This study presents a strategy to design peptides that enable the delivery from endosomes to cytosol by extending the histidine switch principle. By replacing the Arg/Lys residues in cationic cell-penetrating peptides (CPPs) with histidine, the researchers obtained peptides with pH-dependent membrane-perturbation activity, mimicking the endosomal escape of CPPs.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Nanoscience & Nanotechnology
Maximilian A. Beach, Serena L. Y. Teo, Moore Z. Chen, Samuel A. Smith, Colin W. Pouton, Angus P. R. Johnston, Georgina K. Such
Summary: Nanoparticles have the potential to revolutionize drug delivery, but overcoming endosomal escape remains a significant challenge. Recent research focuses on designing nanoparticles that can escape endosomes in response to biological stimuli such as pH changes, which can improve drug delivery efficiency.
ACS APPLIED MATERIALS & INTERFACES
(2022)
Review
Chemistry, Multidisciplinary
Shiqi Wang
Summary: The delivery of emerging biomacromolecular therapeutics faces challenges due to their impermeability to cell membrane and entrapment in endosomes. Anionic pH-responsive amphiphilic carboxylate polymers have been developed to facilitate endosomal escape of these biomacromolecules, with a focus on design, synthesis, mechanism insights, challenges, and future opportunities in the field.
FRONTIERS IN CHEMISTRY
(2021)
Article
Pharmacology & Pharmacy
Tuan Thach Pham, Huan Chen, Phuong Hoang Diem Nguyen, Migara Kavishka Jayasinghe, Anh Hong Le, Minh T. N. Le
Summary: Extracellular vesicles derived from red blood cells (RBCEVs) can release therapeutic RNA/DNA cargos at late endosomes and lysosomes, allowing the cargos to interact with cytoplasmic targets and lead to tumor suppression in vitro and in a murine model of acute myeloid leukemia without significant toxicity. Surface functionalization of RBCEVs with an anti-human CXCR4 antibody enhances gene silencing efficiency by facilitating specific uptake by CXCR4+ leukemic cells. These findings provide insights into the mechanisms of cellular uptake and endosomal escape routes of nucleic acid cargos delivered by RBCEVs and have important implications for improving the RBCEV-based delivery system.
PHARMACOLOGICAL RESEARCH
(2023)
Review
Pharmacology & Pharmacy
Mohammad Hajimolaali, Hosein Mohammadian, Ali Torabi, Amin Shirini, Mostafa Khalife Shal, Hami Barazandeh Nezhad, Sheida Iranpour, Reza Baradaran Eftekhari, Farid Dorkoosh
Summary: CQ is found to interfere with the natural process of endosomal maturation and enhance gene delivery efficiency through electrostatic interactions. Endosomal escape is considered the bottleneck of efficient gene delivery, and CQ as an effective endosomal escape enhancing agent warrants further studies.
EXPERT OPINION ON DRUG DELIVERY
(2021)
Article
Multidisciplinary Sciences
Jinhyung Lee, Ian Sands, Wuxia Zhang, Libo Zhou, Yupeng Chen
Summary: The study introduced a new class of nanoparticles, Janus base nanopieces (NPs), for efficient delivery of RNA cargoes into cell cytoplasm with improved endosomal escape ability and low cytotoxicity. Proof-of-concept experiments indicated that NPs could be promising candidates for future antiviral delivery applications.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Chemistry, Analytical
LianXiao Zhang, Hua Zhong, Hui Zhang, Caifeng Ding
Summary: In this study, a composite nanosystem was designed to utilize DNA structure and CeO2 nanoclusters for miRNA detection and drug delivery, combined with the principles of photodynamic therapy to enhance the cytotoxicity of doxorubicin against cancer cells.
Article
Medicine, Research & Experimental
Marina Buyanova, Ashweta Sahni, Rui Yang, Amar Sarkar, Heba Salim, Dehua Pei
Summary: In this study, analogs of cyclic cell-penetrating peptide 12 (CPP12) were prepared and CPP12-2 was found to have higher cytosolic entry efficiency than CPP12 at low concentrations, making it suitable for the delivery of highly potent cargos.
MOLECULAR PHARMACEUTICS
(2022)
Article
Medicine, Research & Experimental
Marina Buyanova, Ashweta Sahni, Rui Yang, Amar Sarkar, Heba Salim, Dehua Pei
Summary: Cyclic cell-penetrating peptide 12 (CPP12) is highly efficient at delivering cargo molecules into mammalian cells. However, its efficiency is reduced at lower concentrations or in the presence of serum proteins. In this study, CPP12 analogs were prepared with varying hydrophobicity and evaluated for cellular entry. CPP12-2, with a substitution of L-3-benzothienylalanine (Bta) for L-2-naphthylalanine (Nal), showed up to 3.8-fold higher efficiency, especially at low concentrations, due to improved endosomal escape efficiency.
MOLECULAR PHARMACEUTICS
(2022)
Article
Pharmacology & Pharmacy
Leila Mousavifar, Jordan D. Lewicky, Alexis Taponard, Rahul Bagul, Madleen Rivat, Shuay Abdullayev, Alexandrine L. Martel, Nya L. Fraleigh, Arnaldo Nakamura, Frederic J. Veyrier, Hoang-Thanh Le, Rene Roy
Summary: This study reports the chemical synthesis of a novel series of mannosylated neoglycolipids with the goal of further improving on the previous glyconanoparticles. By using a new synthetic method, stable neoglycoliposomes were successfully prepared, and their potential applications in improving cellular uptake and biological activity were explored.
Article
Chemistry, Multidisciplinary
Kefan Song, Dinh Chuong Nguyen, Tran Luu, Omeed Yazdani, Debashish Roy, Patrick S. Stayton, Suzie H. Pun
Summary: We introduce Man-VIPER, a self-assembling polymeric peptide delivery platform that targets dendritic cells and enhances antigen cross-presentation. By encapsulating peptide antigens and facilitating endosomal release, Man-VIPER-NR demonstrates superior efficacy in generating antigen-specific cytotoxic T cells.
JOURNAL OF CONTROLLED RELEASE
(2023)
Article
Nanoscience & Nanotechnology
Wei Zhang, Long Ngo, Simon Chang-Hao Tsao, Dingbin Liu, Yuling Wang
Summary: Cancer-derived sEVs can be used as a drug delivery system that targets cancer cells due to their unique features. However, the oncogenic cargo within them limits their application. We proposed an electroporation-based strategy to extract the endogenous cargo from cancer-derived sEVs, and used membrane fusion to fuse them with liposomes to form hybrid particles. These engineered hybrid particles showed improved targeting ability and higher drug loading ability, and demonstrated enhanced treatment efficiency.
ACS APPLIED MATERIALS & INTERFACES
(2023)
Article
Chemistry, Multidisciplinary
Ajmal Zarinwall, Mazdak Asadian-Birjand, Didem Ag Seleci, Viktor Maurer, Alexandra Trautner, Georg Garnweitner, Hendrik Fuchs
Summary: This study investigates the potential of glycosylated triterpenoids as endosomal escape enhancers to enhance the efficacy of superparamagnetic iron oxide nanoparticle-based toxin therapy. Results show a significant enhancement in tumor cell cytotoxicity and specificity, indicating a promising approach for targeted tumor therapy.
Article
Nanoscience & Nanotechnology
Miguel Gisbert-Garzaran, Daniel Lozano, Kotaro Matsumoto, Aoi Komatsu, Miguel Manzano, Fuyuhiko Tamanoi, Maria Vallet-Regi
Summary: In this study, mesoporous silica nanoparticles were used as a platform to engineer a versatile nanomedicine capable of addressing biological barriers encountered in tumor drug delivery. The nanoparticles demonstrated high biocompatibility and cytotoxic effect in both 2D and 3D in vitro cell cultures and a tumor-bearing chicken embryo model, showing efficient endosomal escape and tumor penetration.
ACS APPLIED MATERIALS & INTERFACES
(2021)
Article
Chemistry, Multidisciplinary
Sangeun Lee, Sarah Nasr, Sari Rasheed, Yun Liu, Olga Hartwig, Cansu Kaya, Annette Boese, Marcus Koch, Jennifer Herrmann, Rolf Mueller, Brigitta Loretz, Eric Buhler, Anna K. H. Hirsch, Claus-Michael Lehr
Summary: The recent success of mRNA vaccines using lipid-based vectors highlights the importance of strategies for nucleotide delivery under the pandemic situation. Although current mRNA delivery is focused on lipid-based vectors, still they need to be optimized for increasing stability, targeting, and efficiency, and for reducing toxicity. In this regard, other vector systems featuring smart strategies such as pH-responsive degradability and endosomal escape ability hold the potential to overcome the current limitations.
JOURNAL OF CONTROLLED RELEASE
(2023)
Article
Nanoscience & Nanotechnology
Hiroyuki Koide, Tomohiro Asai, Hiroki Kato, Norihito Yonenaga, Masafumi Yokota, Hidenori Ando, Takehisa Dewa, Mamoru Nango, Noriyuki Maeda, Naoto Oku
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
(2015)
Article
Biotechnology & Applied Microbiology
Hidenori Ando, Ayaka Okamoto, Masafumi Yokota, Kosuke Shimizu, Tomohiro Asai, Takehisa Dewa, Naoto Oku
JOURNAL OF GENE MEDICINE
(2013)
Article
Chemistry, Medicinal
Tomohiro Asai, Masafumi Yokota, Hideki Isomura, Hiroyuki Koide, Naoyuki Sakurai, Ayaka Okamoto, Hidenori Ando, Takehisa Dewa, Naoto Oku
Summary: This study explores the synthetic lethal interaction between PTEN loss and PARP1 gene silencing in human triple-negative breast cancer cells. The delivery of siPARP1 using polycation liposomes resulted in cytotoxicity in PTEN-null MDA-MB-468 cells, but not in PTEN-positive MDA-MB-231 cells or normal cells. Simultaneous knockdown of PARP1 and PTEN inhibited cell growth in MDA-MB-231 cells. Furthermore, PARP1 knockdown led to increased DNA breaks and apoptosis in MDA-MB-468 cells compared to MDA-MB-231 cells. These findings suggest that synthetic lethality via PARP1 gene silencing holds promise for the treatment of PTEN-null breast cancer.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)