Review
Biochemistry & Molecular Biology
Maria Gagliardi, Ana Tari Ashizawa
Summary: ASOs are a novel and promising class of drugs used to selectively inhibit the translation of disease-associated genes. Challenges in ASO delivery and stability require strategic approaches to overcome these limitations for their full potential in precision medicine.
Article
Pharmacology & Pharmacy
Emma Kay, Rouven Stulz, Cecile Becquart, Jelena Lovric, Carolina Tangemo, Aurelien Thomen, Dzenita Bazdarevic, Neda Najafinobar, Anders Dahlen, Anna Pielach, Julia Fernandez-Rodriguez, Roger Stromberg, Carina Ammala, Shalini Andersson, Michael Kurczy
Summary: Conjugating ASOs to GLP1 is an effective method to knock down targets in pancreatic beta-cells. The study found that ASOs separate from GLP1 relatively early in the endocytic pathway, and the stability of the conjugate may affect GLP1-ASO function.
Article
Biochemistry & Molecular Biology
Monika Mullerova, Dina Maciel, Nadia Nunes, Dominika Wrobel, Marcel Stofik, Lucie Cervenkova St Astna, Alena Krupkova, Petra Curinova, Katerina Novakova, Matej Bozik, Marek Maly, Jan Maly, Joao Rodrigues, Tomas Strasak
Summary: This study presents a stable glycodendrimer (glyco-DDM) series with excellent biocompatibility and potential applications in drug delivery, particularly showing promising results in encapsulating anticancer agents. The glyco-DDM/DOX complexes exhibit gradual and pH-dependent release profiles, preferential internalization in cancer cells, and promising cytotoxic effects on cancer cell lines. The results suggest that novel glycoDDMs and their drug complexes hold great promise in drug delivery and related applications.
Review
Pharmacology & Pharmacy
Raghav Gupta, Sagar Salave, Dhwani Rana, Bharathi Karunakaran, Arun Butreddy, Derajram Benival, Nagavendra Kommineni
Summary: This review explores the potential role of liposomes as a drug delivery system for antisense oligonucleotides (ASOs), particularly in nucleic acid therapeutics. The potential benefits of liposomes as an ASO carrier, including their method of preparation, characterization, routes of administration, and stability, are thoroughly discussed. The major highlights of this review are the novel perspective on therapeutic applications of liposomal ASO delivery in various diseases, such as cancer, respiratory diseases, ophthalmic delivery, infectious diseases, gastrointestinal diseases, neuronal disorders, hematological malignancies, myotonic dystrophy, and neuronal disorders.
Article
Materials Science, Multidisciplinary
Jingjing Gan, Yuxiao Liu, Lingyu Sun, Wenjuan Ma, Guopu Chen, Cheng Zhao, Lihui Wen, Yuanjin Zhao, Lingyun Sun
Summary: This study presents a pH-sensitive drug delivery system for oral treatment of inflammatory bowel disease, which can significantly decrease the production of TNF-alpha in colitis animal models and alleviate colitis symptoms in mice after oral administration. The designed system shows promising potential in treating colon-associated diseases.
APPLIED MATERIALS TODAY
(2021)
Article
Chemistry, Multidisciplinary
Dusan Vobornik, Maohui Chen, Shan Zou, Gregory P. P. Lopinski
Summary: This study identifies two issues that can impact the accuracy of AFM measurements of single-wall carbon nanotubes' diameter. The proposed protocol effectively reduces errors associated with these issues. An analysis method is developed to minimize uncertainties in the extraction of diameters from measured images. The method is successfully applied to measure the diameter distribution of individual highly semiconducting enriched nanotubes in networks.
Article
Chemistry, Multidisciplinary
Derrick Jing Yang Tan, Vee Vee Cheong, Kah Wai Lim, Anh Tuan Phan
Summary: A novel approach using tag phosphoramidites as adaptors enables enzymatic ligation of peptides and oligonucleotides, providing a simple and highly efficient method for the streamlined development and production of peptide/protein-oligonucleotide conjugates.
CHEMICAL COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Kazuki Sumiya, Hiroto Izumi, Yoshiyuki Adachi, Shinichi Mochizuki, Kazuo Sakurai
Summary: This study investigates the structure and nature of different variants of human Dectin-1 expressed on the cellular surface. It reveals the presence of a new N-linked glycosylation site and the important role of glycosylation in the fate and localization of Dectin-1 in cells. The glycosylation is also found to be related to the ingestion of the complex, suggesting additional targets for the complex other than V-1 and V-2.
CARBOHYDRATE RESEARCH
(2023)
Article
Chemistry, Multidisciplinary
Siying Li, Xuelei Pang, Jing Zhao, Qingrong Zhang, Yuping Shan
Summary: Targeted peptides are important in the construction of intelligent drug delivery systems, and the interaction between peptides and receptors is crucial for the efficacy of targeted nano-drugs. Using single-molecule force spectroscopy, this study evaluated the stability and effectiveness of three common peptides targeting specific receptors on living cell surfaces. The T7-TfR bond was found to be the most stable among the three peptide-receptor pairs.
Article
Biochemistry & Molecular Biology
Tetsuhiro Kakimoto, Akira Ogasawara, Kiyoshi Ishikawa, Takashi Kurita, Kumiko Yoshida, Shuichi Harada, Taeko Nonaka, Yoshimi Inoue, Keiko Uchida, Takashi Tateoka, Tetsuya Ohta, Shinji Kumagai, Takashi Sasaki, Hajime Aihara
Summary: In this study, the researchers investigated the therapeutic effect of a novel drug called MT-DUX4-ASO on facioscapulohumeral muscular dystrophy (FSHD). They found that MT-DUX4-ASO can effectively inhibit the expression of the DUX4 gene, improving muscle injury and motor function. The systemic administration of the drug also demonstrated its potential as a promising treatment strategy for FSHD.
Article
Pharmacology & Pharmacy
Tsuyoshi Yamamoto, Yahiro Mukai, Fumito Wada, Chisato Terada, Yukina Kayaba, Kaho Oh, Asako Yamayoshi, Satoshi Obika, Mariko Harada-Shiba
Summary: Development of clinically relevant anti-microRNA antisense oligonucleotides remains a major challenge. One promising configuration called tiny LNA, highly chemically modified with high activity and specificity, shows enhanced in vivo activity with the introduction of N-acetylgalactosamine (GalNAc). GalNAc improves pharmacokinetics, and the ligand should be introduced at the 5' terminus for optimal impact. This strategy may pave the way for clinical application of miRNA-targeting small ASO therapy.
Article
Chemistry, Applied
Dawid Lupa, Wojciech Plazinski, Aneta Michna, Monika Wasilewska, Pawel Pomastowski, Adrian Golebiowski, Boguslaw Buszewski, Zbigniew Adamczyk
Summary: In this study, molecular dynamics modeling was used to predict the properties of chitosan molecules, and experimental results were quantitatively interpreted to explain their behavior under different environmental conditions. The findings provide important references for understanding the electrical properties of chitosan in solution and offer a proper interpretation for previous literature research.
CARBOHYDRATE POLYMERS
(2022)
Article
Biophysics
Joana C. Barbosa, Sonia Goncalves, Marcin Makowski, Itala C. Silva, Tania Caetano, Tanja Schneider, Eva Moesker, Roderich D. Suessmuth, Nuno C. Santos, Sonia Mendo
Summary: Lantibiotics are a promising solution to antibiotic resistance, particularly against Gram-positive bacteria like MRSA and VRE. Work on lichenicidin has shown that the interaction between the two peptides, Blia and Blip, is necessary for full activity against target bacteria. The mechanism of action involves an increase in net surface charge and observed cell surface perturbations that result in leakage of internal contents.
COLLOIDS AND SURFACES B-BIOINTERFACES
(2022)
Review
Pharmacology & Pharmacy
Christopher L. Barkau, Daniel O'Reilly, Seth B. Eddington, Masad J. Damha, Keith T. Gagnon
Summary: CRISPR-based therapeutics have entered clinical trials, but methods to inhibit Cas enzymes in a clinical setting have not yet been demonstrated. The ability to inhibit CRISPR-based gene editing or gene targeting drugs is crucial for establishing safety standards for these therapies, and inhibitors can serve as a failsafe against off-target effects. Among the existing inhibitor technologies, CRISPR SNuBs, small nucleic acid-based CRISPR inhibitors, show promise for clinical application in the near-term.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Nanoscience & Nanotechnology
Xingfei Wei, Alexander Popov, Rigoberto Hernandez
Summary: The electric potential around polyelectrolyte-coated gold nanoparticles is investigated using molecular dynamics simulations. The simulations reveal that the potential decreases with increasing salt concentration and wrapping by polyelectrolytes. The calculated zeta potentials for the nanoparticles at different salt concentrations are reported and compared with theoretical models.
ACS APPLIED MATERIALS & INTERFACES
(2022)
Article
Immunology
Nuria Climent, Juan Ambrosioni, Tania Gonzalez, Cristina Xufre, Maria Casadella, Marc Noguera-Julian, Roger Paredes, Montserrat Plana, Judith Grau-Exposito, Josep Mallolas, Jose Alcami, Sonsoles Sanchez-Palomino, Jose M. Miro
Summary: This study reports a case of a highly controlled HIV infection individual who maintained undetectable viral loads for 15 years after stopping antiretroviral therapy. The researchers found that the high activity of NK cells and CD8 T cells were associated with the control of viral replication.
Article
Biochemistry & Molecular Biology
Viktar Abashkin, Elzbieta Pedziwiatr-Werbicka, Katarzyna Horodecka, Victoriya Zhogla, Egor Ulashchik, Vadim Shmanai, Dzmitry Shcharbin, Maria Bryszewska
Summary: The leading cause of death, cancer, necessitates the development of new effective treatment systems, such as genetic therapy using siRNA. This study explores the use of dendronized and PEGylated silver nanoparticles as potential vectors to deliver proapoptotic siRNA (siMCL-1) to target cells. Through various methods, stable siRNA and AgNP complexes were obtained and shown to efficiently deliver siRNAs to tumor cells, resulting in significant cell death due to apoptosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Philipp F. Popp, Tania Lozano-Cruz, Franziska Duerr, Addis Londaitsbehere, Johanna Hartig, Francisco Javier de la Mata, Rafael Gomez, Thorsten Mascher, Ainhoa Revilla-Guarinos
Summary: The threat of antimicrobial-resistant bacteria is increasing, but the development of new therapeutic countermeasures has stopped. Carbosilane dendritic systems with antimicrobial properties can be used as synthetic molecules for therapeutics. The bow-tie topology of BDTL049 has strong bactericidal properties against Bacillus subtilis. In this study, a fluorescent-labeled version of BDTL049 was synthesized to study its interaction with bacterial membrane, and a mutational study of known resistance determinants was conducted. The compound also showed high cytotoxicity in human cells. These insights highlight the potential and challenges of BDTL049 as an antimicrobial agent.
Article
Medicine, Research & Experimental
Laura Tarancon-Diez, Itziar Carrasco, Santiago Jimenez de Ory, Arantxa Berzosa Sanchez, Alicia Hernanz-Lobo, Marta Montero-Alonso, Montserrat Laguno, Jose I. Bernardino, Luis Lopez-Cortes, Teresa Aldamiz-Echevarria, Pilar Collado, Otilia Bisbal, Gloria Samperiz, Cesar Gavilan, M. Jose Rios, Sofia Ibarra, Maria Luisa Navarro, M. Angeles Munoz-Fernandez
Summary: This study analysed the long-term effect of direct-acting antivirals (DAAs) in HIV/HCV-coinfected youths. The study found that there were significant improvements in liver function and favorable outcomes in haematologic and immune profiles in the long-term after successful response to DAAs. The lipid profile showed changes over time, with increases in total cholesterol, triglycerides, and LDL, and a decrease in HDL, especially in those receiving anti-HIV Protease Inhibitor-based regimens.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Chemistry, Physical
Judith Recio-Ruiz, Riccardo Carloni, Srivathsan Ranganathan, Laura Munoz-Moreno, Maria Jose Carmena, Maria Francesca Ottaviani, Francisco Javier de la Mata, Sandra Garcia-Gallego
Summary: Carbosilane dendrimers are used for the first time to generate functional hydrogels with amphiphilic properties for biomedical applications. The controlled synthesis and lipophilicity of these dendrimers enable precise control of the network and compatibility with poorly soluble drugs. The study demonstrates the impact of the carbosilane dendritic nanodomains on drug encapsulation and release, and shows the effectiveness of curcumin-loaded hydrogels against advanced prostate cancer cells. The dendritic hydrogels also achieve controlled release of ibuprofen through fluoride-promoted esterification.
CHEMISTRY OF MATERIALS
(2023)
Article
Biochemistry & Molecular Biology
Marcin Holota, Sylwia Michlewska, Sandra Garcia-Gallego, Natalia Sanz del Olmo, Paula Ortega, Maria Bryszewska, Francisco Javier de la Mata, Maksim Ionov
Summary: Copper carbosilane metallodendrimers were conjugated with conventional anticancer drugs and showed enhanced effectiveness against cancer cells. The combination therapy significantly decreased cancer cell viability and induced apoptosis and necrosis. The presence of copper ions in the dendrimer structures enhanced the anticancer properties of the whole nanosystem.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Elzbieta Okla, Piotr Bialecki, Marta Kedzierska, Elzbieta Pedziwiatr-Werbicka, Katarzyna Milowska, Samuel Takvor, Rafael Gomez, Francisco Javier de la Mata, Maria Bryszewska, Maksim Ionov
Summary: Drug delivery systems such as dendrimers, liposomes, polymers or gold/silver nanoparticles could advance modern medicine by overcoming biological barriers. This study evaluated the biophysical properties and biological safety of pegylated gold nanoparticles complexed with therapeutic siRNA against APOE4. The results showed that the complexes were stable and non-toxic to healthy cells, suggesting their potential use in delivering nucleic acids and treating neurodegenerative diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Nanoscience & Nanotechnology
Michal Gorzkiewicz, Monika Marcinkowska, Maciej Studzian, Iwona Karwaciak, Lukasz Pulaski, Barbara Klajnert-Maculewicz
Summary: This study developed an innovative nanocarrier based on PAMAM dendrimer to increase the concentration of mesalazine in intestinal epithelial cells, thereby enhancing its anti-inflammatory potential. The covalent PAMAM-mesalazine conjugate was synthesized and characterized, and it was found that the drug successfully attached to the dendrimer. The use of PAMAM as a carrier improved cellular uptake and anti-inflammatory activity of mesalazine.
INTERNATIONAL JOURNAL OF NANOMEDICINE
(2023)
Article
Pharmacology & Pharmacy
Sylwia Michlewska, Marek Maly, Dagmara Wojkowska, Kamil Karolczak, Elzbieta Skiba, Marcin Holota, Malgorzata Kubczak, Paula Ortega, Cezary Watala, F. Javier de la Mata, Maria Bryszewska, Maksim Ionov
Summary: In this study, a carbosilane metallodendrimer containing a ruthenium complex was conjugated with anti-cancer drugs, and it was found that the ruthenium enhanced the effectiveness of the drugs. The results showed that stable nanocomplexes were formed between the dendrimer and the drugs, improving their efficacy against cancer cells.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2023)
Article
Biochemistry & Molecular Biology
K. Sztandera, M. Gorzkiewicz, E. A. Zizzi, N. Dybczak, L. Poltorak, M. A. Deriu, B. Klajnert-Maculewicz
Summary: Due to the negative charge of rose bengal (RB) molecule, its entry into cells is hindered. This study investigates the involvement of organic anion transporting polypeptides (OATPs) in cellular uptake of RB. Experimental analysis and simulations indicate that RB only interacts with the surface of cellular membranes and requires OATPs for intracellular transport. The differences in uptake of RB in liver and intestinal cell lines suggest the importance of OATPs in cellular uptake.
BIOELECTROCHEMISTRY
(2023)
Article
Medicine, Research & Experimental
Laura Tarancon-Diez, Marianela Iriarte-Gahete, Pilar Sanchez-Mingo, Guillermo Perez-Cabeza, Fernando Romero-Candau, Yolanda M. Pacheco, Manuel Leal, Maria Angeles Munoz-Fernandez
Summary: The study evaluated the safety and effectiveness of a generic intravenous iron treatment in Spanish patients with absolute iron deficiency. The results showed improvements in iron-related biomarkers, anemia, and ferritin levels. The recurrence of iron deficiency was associated with baseline iron stores depletion and sTfR/hepcidin ratio.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Infectious Diseases
Maria Jose Munoz-Gomez, Maria Martin-Vicente, Sara Vigil-Vazquez, Itziar Carrasco, Alicia Hernanz Lobo, Vicente Mas, Monica Vazquez, Angela Manzanares, Olga Cano, Clara Zamora, Roberto Alonso, Daniel Sepulveda-Crespo, Laura Tarancon-Diez, Maria angeles Munoz-Fernandez, Mar Munoz-Chapuli, Salvador Resino, Maria Luisa Navarro, Isidoro Martinez
Summary: Pregnant women who received COVID-19 mRNA vaccines have high levels of SARS-CoV-2 S antibodies, which can be transferred to their infants. However, the antibody levels decrease significantly in infants at 2 to 3 months old.
