Article
Multidisciplinary Sciences
Jiaxuan Chen, Dandan Zhu, Baoping Lian, Kangjie Shi, Peng Chen, Ying Li, Wenyi Lin, Ling Ding, Qiulin Long, Yang Wang, Erik Laurini, Wenjun Lan, Yun Li, Aura Tintaru, Caoyun Ju, Can Zhang, Sabrina Pricl, Juan Iovanna, Xiaoxuan Liu, Ling Peng
Summary: Nucleic acid therapeutics serve as an important drug modality for targeting undruggable targets, responding to evolving pathogens, and precision medicine at the gene level. Dendrimers, as precision delivery systems, have been utilized for selective and on-demand delivery of DNA and siRNA. The properties and performance of these dendrimers were systematically studied, and they exhibited cargo-adaptive and selective delivery, tumor targeting, and redox-responsive cargo release. The dendrimers outperformed currently available vectors in tumor and cancer cell-specific delivery of siRNA and DNA therapeutics in various cancer models. This study provides a pathway for engineering tailor-made vectors for nucleic acid delivery and precision medicine.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Chemistry, Multidisciplinary
Aazam Shaikh, Prashant Kesharwani, Virendra Gajbhiye
Summary: Dendrimers have a wide range of applications in biomedical fields, including cargo delivery, nucleic acid delivery, and macromolecule delivery. They can also be used to crosslink synthetic and natural polymeric scaffolds and mimic the extracellular matrix. Dendrimers play a crucial role in regulating cell behavior and delivering bioactive molecules, and have shown significant results in stem cell survival, osteogenesis, and repair.
JOURNAL OF CONTROLLED RELEASE
(2022)
Article
Chemistry, Multidisciplinary
Wenzheng Zhang, Dinesh Dhumal, Xiaolei Zhu, Brigino Ralahy, Aleksandra Ellert-Miklaszewska, Jing Wu, Erik Laurini, Yi-Wen Yao, Chai-Lin Kao, Juan L. Iovanna, Sabrina Pricl, Bozena Kaminska, Yi Xia, Ling Peng
Summary: In this study, novel bola-amphiphilic glycodendrimers with mannose and glucose terminals, and a hydrophobic thioacetal core responsive to reactive oxygen species, were reported. The unique bola-amphiphilic feature enhanced the binding to lectin compared to conventional amphiphiles. Moreover, these dendrimers effectively targeted mannose receptors and glucose transporters on cell surfaces, exhibiting great promise for targeted delivery.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Paul Klemm, Jana Solomun, Marko Rodewald, Maren T. Kuchenbrod, Veit G. Hansch, Friederike Richter, Juergen Popp, Christian Hertweck, Stephanie Hoeppener, Colin Bonduelle, Sebastien Lecommandoux, Anja Traeger, Stephanie Schubert
Summary: This study investigates the potential of amphiphilic and potentially biodegradable polypeptides for gene delivery. By studying the influence of different proportions of aliphatic and cationic side chains on the physicochemical properties of the polypeptides, the researchers were able to identify the best performer for transfection efficiency. Detailed studies of the transfection mechanism revealed the strong interaction of the identified polypeptide with cell membranes, promoting efficient cell uptake and release. The study demonstrates the great potential of polypeptides for gene delivery.
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
Dinesh Dhumal, Bar Maron, Einav Malach, Zhenbin Lyu, Ling Ding, Domenico Marson, Erik Laurini, Aura Tintaru, Brigino Ralahy, Suzanne Giorgio, Sabrina Pricl, Zvi Hayouka, Ling Peng
Summary: The urgent need for innovative antibacterial agents due to the antibiotic resistance crisis is addressed in this study. The researchers developed antibacterial candidates based on self-assembled supramolecular dendrimer nanosystems, which exhibited strong antibacterial activity and prevented biofilm formation.
Article
Biochemistry & Molecular Biology
Zhibo Yu, Nicolas Tsapis, Francois Fay, Liang Chen, Andrii Karpus, Xiangyang Shi, Catherine Cailleau, Samuel Garcia Perez, Nicolas Huang, Juliette Vergnaud, Serge Mignani, Jean-Pierre Majoral, Elias Fattal
Summary: Small interfering RNA (siRNA) shows potential in treating rheumatoid arthritis by inhibiting major cytokines like tumor necrosis factor-alpha (TNF-alpha). Researchers have developed original cationic amphiphilic phosphorus dendrons that can form dendriplexes with TNF-alpha siRNA. These dendriplexes protect siRNA from degradation and enhance macrophage uptake, leading to significant inhibition of TNF-alpha expression and anti-inflammatory effects in in vitro and in vivo models. This opens up important perspectives for using these original amphiphilic dendrons in chronic inflammatory diseases.
Article
Chemistry, Multidisciplinary
Ramya Kannan, Ayan Datta, Palani Prabakaran, Edamana Prasad, Vignesh Muthuvijayan
Summary: A rationally designed amphiphilic poly(aryl ether)-based dendrimer self-assembles into nanomicelles with tunable morphology by varying the hydrophilic chain length. These 30 nm-sized dendrimer nanomicelles successfully entrapped Doxorubicin, exhibited sustained release of the drug, and effectively penetrated cancer cells through caveolae-dependent endocytosis.
CHEMICAL COMMUNICATIONS
(2021)
Article
Pharmacology & Pharmacy
Dandan Zhu, Huanle Zhang, Yuanzheng Huang, Baoping Lian, Chi Ma, Lili Han, Yu Chen, Shengmei Wu, Ning Li, Wenjie Zhang, Xiaoxuan Liu
Summary: The drug-delivery nanosystem based on amphiphilic peptide dendrimers effectively overcomes drug resistance and improves the uptake and release of anticancer drugs, offering new hope for cancer therapy.
Article
Chemistry, Analytical
Xing Huang, Meng Chen, Zhan Huang, Yanfei Zhang, Taorong Shen, Yakun Shi, Yanli Tong, Xiaoyong Zou, Si-Yang Liu, Jianhe Guo, Zong Dai
Summary: In this study, a novel DNA nanodevice was proposed for dual-biomarker sensing, enabling highly specific imaging of cancer cells. By performing transmembrane logic operations from the cell membrane to the cytoplasm, the nanodevice achieved reliable analysis of intracellular biomarkers such as nucleolin protein and microRNAs.
ANALYTICAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Yunfeng Yan, Fangtao Zhu, Huahui Su, Xiaomin Liu, Qidi Ren, Fangqian Huang, Wenbo Ye, Mengdan Zhao, Yunchun Zhao, Junpeng Zhao, Qi Shuai
Summary: This study constructed a library of 144 functional triblock polymers and discovered three effective carriers for siRNA delivery through high-throughput screening. In vitro evaluation showed that the siRNA-loaded nanoparticles fabricated with these polymers effectively silenced luciferase genes with low cytotoxicity. The chemical structure of the polymers significantly affected the physicochemical properties and in vitro delivery efficacy of the siRNA-loaded nanoparticles. In vivo experiments demonstrated that siRNA nanoparticles based on a specific polymer accumulated at tumor sites, suggesting the potential of this polymer in improving blood circulation and biodistribution of siRNA nanoparticles. This functional triblock polymer platform holds great potential in siRNA-based cancer therapies.
MACROMOLECULAR BIOSCIENCE
(2022)
Article
Engineering, Biomedical
Jin Qiu, Qianqian Fan, Sainan Xu, Dongmei Wang, Juntong Chen, Sainan Wang, Tianhui Hu, Xinran Ma, Yiyun Cheng, Lingyan Xu
Summary: This study discovered a highly efficient fluoropolypeptide for the delivery of siRNA-based therapeutics into adipocytes and adipose tissues, showing potential for gene therapy of obesity and metabolic disorders.
Article
Pharmacology & Pharmacy
Olga Osipova, Nataliia Zakharova, Ivan Pyankov, Anna Egorova, Anastasia Kislova, Antonina Lavrentieva, Anton Kiselev, Tatiana Tennikova, Evgenia Korzhikova-Vlakh
Summary: The effective delivery of nucleic acid therapeutics into tumor cells is a crucial aspect of cancer gene therapy. In this study, a series of amphiphilic positively charged biocompatible pH-sensitive polypeptides were synthesized for siRNA delivery. These polypeptides showed self-assembly in aqueous media and formed nanoparticles with favorable characteristics for cellular uptake. The successful down-regulation of gene expression in breast cancer cells demonstrated the potential of these polypeptides as promising non-viral candidates for siRNA delivery.
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Dapeng Zhang, Elena N. Atochina-Vasserman, Devendra S. Maurya, Ning Huang, Qi Xiao, Nathan Ona, Matthew Liu, Hamna Shahnawaz, Houping Ni, Kyunghee Kim, Margaret M. Billingsley, Darrin J. Pochan, Michael J. Mitchell, Drew Weissman, Virgil Percec
Summary: Efficient delivery of nucleic acids is crucial for genetic nanomedicine. While viral vectors are highly efficient, they can also cause severe immune responses, toxicity, and mutations. Nonviral lipid nanoparticles containing specific components show promise for mRNA delivery, but challenges such as stability at low temperatures need to be addressed.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Multidisciplinary
Yuansong Wei, Xudong Li, Juanhui Lin, Yang Zhou, Jiandong Yang, Mengying Hou, Fan Wu, Jing Yan, Chenglong Ge, Duanmin Hu, Lichen Yin
Summary: A small-sized fluorinated nanocapsule (F-NCs) is developed for efficient oral delivery of siRNA for anti-inflammation treatment. The F-NCs possess a stable structure with excellent mucus penetration and intestinal transport capabilities. The released siRNA can effectively silence the target gene and exhibit pronounced anti-inflammatory efficacy.
ADVANCED MATERIALS
(2023)
Article
Engineering, Biomedical
Ruihong Li, Juan Liu, Jie Ma, Xuer Sun, Yi Wang, Jiexin Yan, Qunfang Yu, Jinmei Diao, Chun Yang, Lola M. Reid, Yunfang Wang
Summary: The liver functions depend on interactions between parenchymal cells and the microenvironment, with biological macromolecules in the matrix playing a key role. Rat liver biomatrix scaffold prepared from adult rats is more effective in enhancing hepatic spheroid function. Fibronectin and fibrinogen show potential for improving hepatocyte function, promoting cell aggregation and activating Wnt/beta-catenin pathway.
Article
Biochemistry & Molecular Biology
Chaima Cherif, Dang Tan Nguyen, Clement Paris, Thi Khanh Le, Thibaud Sefiane, Nadine Carbuccia, Pascal Finetti, Max Chaffanet, Abdessamad El Kaoutari, Julien Vernerey, Ladan Fazli, Martin Gleave, Mohamed Manai, Philippe Barthelemy, Daniel Birnbaum, Francois Bertucci, David Taieb, Palma Rocchi
Summary: Menin (MEN1) protein is highly regulated by HSP27, overexpressed in high-grade PC and CRPC, and high MEN1 mRNA expression is associated with decreased biochemical relapse-free and overall survival. Silencing Menin helps inhibit CRPC cell proliferation, tumor growth, and restore chemotherapeutic sensitivity.
Article
Materials Science, Biomaterials
Juan Liu, Xixue Hu, Shubin Jin, Xing-Jie Liang, Xiaowei Ma
Summary: The study introduced a multifunctional mesoporous silica nanoparticle design with pH-triggered chemotherapy release and dual-targeting functions. These nanoparticles efficiently delivered anti-tumor drugs into lysosomes and showed great potential as a novel drug carrier in therapeutic applications against cancers.
JOURNAL OF MATERIALS CHEMISTRY B
(2022)
Article
Pharmacology & Pharmacy
Juan Liu, Tingting Li, Ruihong Li, Jie Wang, Pengyan Li, Ming Niu, Le Zhang, Chunyu Li, Tao Wang, Xiaohe Xiao, Jia-bo Wang, Yunfang Wang
Summary: The complexity of chemical components in herbal medicines poses challenges for toxicity research. This study successfully differentiated the hepatotoxic potential of two stereoisomers using a hepatic organoids-based in vitro system and high content imaging. It also identified the mitochondrial injury mechanism of the toxic isomer and demonstrated the usefulness of the organoids-based high-content imaging approach in evaluating and predicting organ toxicity of natural products.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Thi Khanh Le, Chaima Cherif, Kenneth Omabe, Clement Paris, Francois Lannes, Stephane Audebert, Emilie Baudelet, Mourad Hamimed, Dominique Barbolosi, Pascal Finetti, Cyrille Bastide, Ladan Fazli, Martin Gleave, Francois Bertucci, David Taieb, Palma Rocchi
Summary: The heat shock protein 27 (Hsp27) plays a crucial role in the progression of castration-resistant prostate cancer (CRPC), and an antisense oligonucleotide (ASO) against Hsp27 has been evaluated in clinical trials. This study demonstrates that Hsp27 regulates the expression of the human DEAD-box protein 5 (DDX5) and identifies DDX5 as a potential therapeutic target for CRPC treatment.
Article
Chemistry, Multidisciplinary
A. Ya-Ting Huang, C. -L. Kao, A. Selvaraj, L. Peng
Summary: Dendrimers have a unique dendritic structure and multivalent cooperativity, making them promising for various applications. However, dendrimer synthesis faces challenges with structural defects and purification. Solid-phase synthesis can overcome these problems by enabling complete reactions and facilitating purification. This review discusses the challenges and current research in solid-phase dendrimer synthesis, as well as efforts to develop more effective methods.
MATERIALS TODAY CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Mrunal Patil, Krykun Serhii, Frederic Garzino, Quentin Gobert, Suzanne Giorgio, Jean-Manuel Raimundo, Jean-Michel Bolla, Michel Camplo
Summary: Antibiotic resistance has led to the need for new treatments against multidrug-resistant microorganisms. 5-fluorouracil (5-FU) has been proposed as an alternative due to its intrinsic antibacterial property, but its high toxicity at high doses raises concerns. This study synthesized 5-FU derivatives and assessed their efficacy against pathogenic bacteria, finding that compounds with tri-hexylphosphonium substitution on both nitrogen groups of 5-FU had significant activity against both Gram-positive and Gram-negative bacteria. Compound 6c, with an asymmetric linker group, had the highest antibacterial efficacy.
ARCHIV DER PHARMAZIE
(2023)
Article
Chemistry, Physical
D. Marin, G. Gerbaud, O. Margeat, F. Ziarelli, F. Ferrer, O. Ouari, A. Campos, S. Bertaina, A. Savoyant
Summary: The combination of nuclear and electron magnetic resonance techniques was used to study the light-induced magnetic state at the surface of chemically prepared zinc oxide nanoparticles. It was found that the observed four-line structure arises from surface-located methyl radicals and is replaced by trideuteromethyl with functionalization. Advanced pulse-EPR techniques reveal the modulation and correlations between different EPR transitions of the radicals.
JOURNAL OF CHEMICAL PHYSICS
(2023)
Article
Chemistry, Medicinal
Xue Yang, Karine Varini, Magali Godard, Fanny Gassiot, Rose Sonnette, Geraldine Ferracci, Belinda Pecqueux, Valerie Monnier, Laurence Charles, Sebastien Maria, Micael Hardy, Olivier Ouari, Michel Khrestchatisky, Pascaline Lecorche, Guillaume Jacquot, David Bardelang
Summary: In this study, a cyclic peptide (VH4127) targeting the LDL receptor (LDLR) was noncompetitively coupled to cucurbit[7]uril (CB[7] ) to develop a new drug delivery system (DDS) named CB[7]-VH4127, which maintained its binding affinity to LDLR. The resulting supramolecular complex A680-Ada & BULL;CB[7]-VH4127 demonstrated conserved LDLR-binding potential and improved LDLR-mediated endocytosis and intracellular accumulation in LDLR-expressing cells. This new DDS opens up new possibilities for targeting and intracellular delivery to LDLR-expressing tissues or tumors.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Peng Zhang, Zhi Li, Weiling Cao, Jingjie Tang, Yi Xia, Ling Peng, Jing Ma
Summary: The study presents an effective strategy for treating metastatic breast cancer by using a self-assembling dendrimer nanosystem to deliver siRNA inhibiting PDK1 and modulating cancer metabolism, while promoting PD-1/PD-L1 pathway-based immunotherapy. This nanosystem, named PPD, effectively inhibits tumor growth and metastasis without notable toxicity in tumor-bearing mouse models. The results highlight the potential use of PPD as an effective and safe tumor-targeting therapy for breast cancer.
ADVANCED MATERIALS
(2023)
Article
Physics, Atomic, Molecular & Chemical
Isaure Sergent, Abel Idrice Adjieufack, Anouk Gaudel-Siri, Didier Siri, Laurence Charles
Summary: The need for appropriate standards to calibrate ion arrival times in traveling wave ion mobility (TWIM) for collision cross section (CCS) measurements, especially for multiply charged anions, is addressed by a new approach implemented in the IMSCal software. The approach involves training a mathematical model with different combinations of phosphoric acid clusters and deprotonated polyalanine standards to derive CCS values for TWIM-measured multiply charged anions. The inclusion of standards with different charge states, as well as matching the charge state of the analytes, is crucial for accurate CCS determination.
INTERNATIONAL JOURNAL OF MASS SPECTROMETRY
(2023)
Article
Pharmacology & Pharmacy
Sandra Udu-Ituma, Jose Adelaide, Thi Khanh Le, Kenneth Omabe, Pascal Finetti, Clement Paris, Arnaud Guille, Francois Bertucci, Daniel Birnbaum, Palma Rocchi, Max Chaffanet
Summary: The luminal B subtype of breast cancer is associated with aggressive behavior and poor prognosis. Endocrine therapy has contributed to decreased mortality, but resistance to estrogen receptor modulators such as tamoxifen is common. The overexpression of ZNF703 gene has been implicated in drug resistance, making it a potential target for treatment.
Article
Engineering, Biomedical
Marco Viola, Claudia Migliorini, Fabio Ziarelli, Stephane Viel, Claudia Cencetti, Daniel Di Risola, Luciana Mosca, Laura Masuelli, Pietro Matricardi, Chiara Di Meo
Summary: The novel amphiphilic polyacrylate grafted with cholesterol moieties, PAAbCH, has been extensively characterized and investigated, showing promising potential as an innovative excipient. It can enhance drug solubility, viscosity, and emulsifying properties, and forms stable hydrogel complexes with chitosan.
JOURNAL OF FUNCTIONAL BIOMATERIALS
(2023)
Article
Chemistry, Multidisciplinary
Samuel F. Cousin, Colan E. Hughes, Fabio Ziarelli, Stephane Viel, Giulia Mollica, Kenneth D. M. Harris, Arthur C. Pinon, Pierre Thureau
Summary: Solid-state DNP NMR can improve the detection of minor solid phases in heterogeneous materials. We demonstrated the use of NMR contrast based on DNP-enhanced polarization transport for the early detection of a small amount of a minor polymorphic phase within a major polymorph. We also showed that this approach allows for quantitative information on the spatial distribution of the two polymorphs.
Review
Materials Science, Biomaterials
Christina Galanakou, Dinesh Dhumal, Ling Peng
Summary: With the increasing concern for antimicrobial resistance, there is a need for novel antimicrobial agents that can effectively combat bacterial resistance without inducing further resistance development. Amphiphilic dendrimers are emerging as a promising solution, as they mimic antimicrobial peptides and possess stable dendritic structures that resist enzymatic degradation. These dendrimers can be precisely designed to optimize their hydrophobic-hydrophilic balance, resulting in potent antibacterial activity and minimal adverse effects. This review explores the challenges, mechanisms, and future prospects of using amphiphilic dendrimers as antibiotic substitutes to combat antimicrobial resistance.
BIOMATERIALS SCIENCE
(2023)
