Article
Multidisciplinary Sciences
Yuan Rui, David R. Wilson, Stephany Y. Tzeng, Hannah M. Yamagata, Deepti Sudhakar, Marranne Conge, Cynthia A. Berlinicke, Donald J. Zack, Anthony Tuesca, Jordan J. Green
Summary: Nanoparticle-based mRNA therapeutics show great promise, but cellular internalization and endosomal escape pose challenges for cytosolic delivery. Researchers developed a dual nanoparticle uptake and endosomal disruption assay, which can detect cellular internalization and endosomal disruption. The study found that this assay has higher predictive capacity for mRNA delivery compared to conventional polymer and nanoparticle characteristics.
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
Biology
Taishi Yasukawa, Arisa H. Oda, Takahiro Nakamura, Naohisa Masuo, Miki Tamura, Yuriko Yamasaki, Makoto Imura, Takatomi Yamada, Kunihiro Ohta
Summary: The TAQing2.0 system enables the delivery of endonucleases into the cell nucleus of asexual industrial microorganisms, inducing genomic rearrangements and generating mutants with altered phenotypes, without the need for introducing foreign DNA.
COMMUNICATIONS BIOLOGY
(2022)
Article
Medicine, Research & Experimental
Melissa L. Jagrosse, Uday K. Baliga, Christopher W. Jones, Jade J. Russell, Claudia I. Garcia, Rauf Ahmad Najar, Arshad Rahman, David A. Dean, Bradley L. Nilsson
Summary: In this study, a series of modified cyclic amphipathic cell-penetrating peptides (CAPs) were used to investigate their effects on siRNA-binding efficiency, cellular delivery and knockdown efficiency, and endocytic uptake mechanism. The results show that CAP sequences with strong cationic character and aromatic residues can interact most effectively with siRNA. Cationic charge and disulfide-constrained cyclization of CAPs improve the uptake of siRNA, while net neutral CAPs and an acyclic peptide show less-efficient siRNA translocation. All tested CAPs facilitate efficient siRNA target gene knockdown, and the best CAPs enable more than 80% knockdown. There is a moderate correlation between gene knockdown efficiency and CAP-siRNA-binding affinity. Most CAP-siRNA nanoparticles deliver siRNA through clathrin- and caveolin-mediated endocytosis. These findings provide valuable insights into the design of CAPs for siRNA delivery and the mechanism of siRNA translocation.
MOLECULAR PHARMACEUTICS
(2023)
Article
Biochemistry & Molecular Biology
Zhen Shi, Yuhan Yang, Ziyang Guo, Shun Feng, Yu Wan
Summary: In this study, a novel redox- and enzyme-responsive fluorinated polyarginine (PFC-PR) was developed as an anti-cancer siRNA carrier. The PFC-PR showed efficient binding with siRNA and enhanced stability, serum tolerance, cellular uptake, and endosome escape. It also exhibited responsiveness to cancer cell-specific conditions, leading to enhanced siRNA release and cancer-targeting ability. Overall, the PFC-PR demonstrated good biocompatibility and high gene silencing efficiency, making it a potential candidate for anti-cancer gene therapy applications.
BIOORGANIC CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Ole Tietz, Fernando Cortezon-Tamarit, Rod Chalk, Sarah Able, Katherine A. Vallis
Summary: This study identifies a method to deliver antibodies and antibody fragments into the cytosol and nucleus of cells using trimeric cell-penetrating peptides (CPPs). By utilizing these peptides, it overcomes a major obstacle in intracellular targeting, which is the entrapment of biomacromolecules in the endosome.
Review
Agriculture, Multidisciplinary
Jihong Hu, Guanglong Chen, Kui Xu, Jun Wang
Summary: This review summarizes the processes of cadmium uptake, translocation, and accumulation in cereal crops, as well as efficient measures to reduce cadmium uptake and potential remediation strategies. The findings provide insights into innovative approaches for reducing cadmium accumulation in cereal grains and sustainable management of cadmium-contaminated paddy fields.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Shogo Nishida, Yuuki Takashima, Ryotaro Udagawa, Hisako Ibaraki, Yasuo Seta, Hiroshi Ishihara
Summary: This study aimed to develop a nanocarrier for the non-invasive delivery of siRNA to the retina by eyedrops. A hybrid nanocarrier based on a multifunctional peptide and liposomes was prepared and optimized. The results showed that the nanocarrier significantly enhanced siRNA transfection efficiency and effectively suppressed vascular endothelial growth factor expression in rat retinal pigment epithelium cells.
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
Medicine, Research & Experimental
Ryley Hall, Abdulaziz Alasmari, Saghar Mozaffari, Parvin Mandipoor, Keykavous Parang, Hamidreza Montazeri Aliabadi
Summary: Researchers developed a multicomponent delivery system called peptide lipid-associated nucleic acids (PLANAs) to encapsulate siRNA efficiently and achieve protein silencing in cancer cells.
MOLECULAR PHARMACEUTICS
(2021)
Article
Chemistry, Organic
Alexander Pontarelli, Jiang Tian Liu, Hourieh Movasat, Sarah Menard, Jung Kwon Oh, Christopher J. Wilds
Summary: The synthesis and incorporation of a tosylated phosphoramidite linker containing a disulfide bond is described. This linker was efficiently incorporated into short DNA and RNA oligomers using automated solid phase synthesis, allowing for the expansion of strategies for bifunctional modification of synthetic oligonucleotides for conjugation applications.
Article
Chemistry, Multidisciplinary
Natalia Vtyurina, Christoffer Aberg, Anna Salvati
Summary: Live cell imaging is a powerful tool for understanding how nano-sized objects are taken up and trafficked by cells. The study found high variability in intracellular trafficking kinetics between individual cells and how nanoparticle properties affect cellular uptake and intracellular distribution kinetics.
Article
Medicine, Research & Experimental
Shahd Abuhelal, Miguel N. Centelles, Michael Wright, A. James Mason, Maya Thanou
Summary: RNAi has potential as a cancer therapeutic approach, but delivering siRNA to tumors efficiently is a challenge. In this study, a complex consisting of siRNA, cationic lipids, and pH-responsive peptides was developed to overcome the barriers in siRNA delivery. The complex encapsulates siRNA effectively, protects it from degradation, and promotes endosomal escape, leading to more effective gene silencing. In mice with breast cancer xenografts, the complex accumulated in tumors following focused ultrasound (FUS) treatments. Combining the complex with FUS treatment offers a promising route for robust in vivo gene delivery.
MOLECULAR PHARMACEUTICS
(2023)
Article
Biotechnology & Applied Microbiology
Jang Hyuk Bang, Yeong Chae Ryu, Kyung Ah Kim, Byeong Hee Hwang
Summary: This study developed a self-assembled nanocomplex combining fusion peptides and small RNAs for efficient, stable, and targeted delivery to breast cancer cells. The results showed that the nanocomplexes exhibited prolonged stability, enhanced cellular uptake, and effectively inhibited breast cancer cell growth, with no significant cytotoxicity observed in in vitro and in vivo tests.
BIOCHEMICAL ENGINEERING JOURNAL
(2022)
Article
Medicine, Research & Experimental
Keisuke Tanaka, Takumi Okuda, Yuuya Kasahara, Satoshi Obika
Summary: In this study, aptamers that efficiently internalize into A549 cells were successfully obtained using an evolutionary selection approach. The conjugation of these aptamers with MALAT1-targeting antisense oligonucleotides showed enhanced activity when endosomal/lysosomal escape was improved with the addition of chloroquine. This highlights the importance of endosomal/lysosomal escape for intracellular delivery of antisense oligonucleotides by aptamers.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2021)