Article
Chemistry, Multidisciplinary
Delu Che, Chenfei Wang, Zhili Li, Kaixuan Wang, Shuaiwei Sun, Xinyue Zhang, Yi Li, Zhengju Chen, Lei Guo, Yajing Hou, Dezhong Zhou, Songmei Geng
Summary: Suspension cells play a crucial role in many biological processes. However, introducing exogenous genes into suspension cells for gene regulation is challenging. By designing and synthesizing highly branched poly(ss-amino ester) (HPAE), we enhance the interactions of polyplexes with cellular membranes, resulting in improved gene transfection efficiency in mast cells (MCs) without cytotoxicity. This study establishes a reliable non-viral platform for efficient gene transfection of suspension cells.
CHINESE CHEMICAL LETTERS
(2023)
Article
Chemistry, Multidisciplinary
Chenfei Wang, Litao Sun, Qiuxia Li, Zhili Li, Chengyuan Xu, Xinyue Zhang, Jianjun Shi, Hao Zhou, Wenxin Wang, Dezhong Zhou
Summary: By using a stepwise precipitation strategy, highly branched poly(beta-amino ester)s (HPAEs) were fractionated, and it was found that the molecular weight (MW) significantly affects the transfection activity and cytotoxicity of HPAEs. Intermediate MW of HPAEs shows higher transfection efficiency and cell viability. Mechanistic studies reveal that the intermediate MW of HPAEs has stronger DNA binding affinity, leading to the formation of smaller polyplexes with more positive zeta potential. This study provides a simple strategy to fractionate HPAEs and offers new insights into the structure-property relationship for potential clinical translation in gene therapy.
CHINESE CHEMICAL LETTERS
(2023)
Article
Materials Science, Biomaterials
Ali Alazzo, Nurcan Gumus, Pratik Gurnani, Snjezana Stolnik, Ruman Rahman, Keith Spriggs, Cameron Alexander
Summary: Higher molar mass derivatives of poly(lysine) were found to yield smaller polyplexes with greater affinity for siRNA and higher transfection efficiency, although they may come with some cytotoxicity. Histidinylation improved biocompatibility slightly, but did not significantly enhance gene silencing efficiency compared to non-histidinylated derivatives.
JOURNAL OF MATERIALS CHEMISTRY B
(2022)
Article
Pharmacology & Pharmacy
Sajid Iqbal, Zhongxi Zhao
Summary: The unique properties of polymers have made significant contributions to drug delivery systems, with block copolymers showing excellent performance in drug targeting. Poly(beta-amino esters) copolymers have demonstrated extraordinary efficiency in designing pre-defined nanostructures and overcoming cellular barriers, with the potential for customized therapeutic functions such as high stability and stimuli-responsive release.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2022)
Article
Biochemistry & Molecular Biology
Dagmar Fischer, Niels Dusek, Konrad Hotzel, Thomas Heinze
Summary: Dextran-formamidine esters with varying degrees of substitution were successfully synthesized and demonstrated improved DNA binding and high transfection rates in CHO-K1 cells. These results suggest that dextran-formamidine esters are promising materials for safe and efficient gene delivery.
MACROMOLECULAR BIOSCIENCE
(2021)
Article
Polymer Science
Mehmet Koray Gok, Kamber Demir, Erdal Cevher, Serhat Pabuccuoglu, Saadet Ozgumus
Summary: This study successfully synthesized branched poly(beta-aminoester) (PBAE) with high transfection efficiency and prepared PBAE nanoparticles using two different methods. In vitro studies on primary ovine fibroblast cells showed that the formulated PBAE had a high transfection efficiency, exhibiting almost 1.5 times more efficiency than the commercial product Lipofectamine.
EUROPEAN POLYMER JOURNAL
(2022)
Article
Engineering, Biomedical
Yuheng Cao, Haobo He, Kaili Cao, Yongyang Liu, Dehua Huang, Tuanwei Li, Guangcun Chen
Summary: In this study, a novel polymer STBD was developed for efficient gene delivery into neural stem cells. The polymer showed high gene load capacity and biocompatibility, and interfered with SOX9 expression to enhance neuronal differentiation. This non-viral gene delivery approach holds great potential in stem cell-based regenerative therapy for neurodegenerative diseases.
BIOMEDICAL MATERIALS
(2022)
Article
Polymer Science
Yinghao Li, Xianqing Wang, Zhonglei He, Zishan Li, Melissa Johnson, Bei Qiu, Rijian Song, A. Sigen, Irene Lara-Saez, Jing Lyu, Wenxin Wang
Summary: In this study, the effect of molecular weight components on gene delivery efficiency of highly branched poly(beta-amino ester) (HPAE) was investigated. It was found that removing small molecular weight portions from HPAE significantly enhanced its transfection performance. By applying a structural optimization strategy, a highly efficient HPAE gene delivery vector was developed, which opens up new opportunities for gene therapy applications.
Article
Biochemistry & Molecular Biology
Jonathan O'Keeffe Ahern, Irene Lara-Saez, Dezhong Zhou, Rodolfo Murillas, Jose Bonafont, Angeles Mencia, Marta Garcia, Dario Manzanares, Jennifer Lynch, Ruth Foley, Qian Xu, A. Sigen, Fernando Larcher, Wenxin Wang
Summary: This study demonstrates the potential of the HPAE-EB polymer for CRISPR-Cas9 genome editing, achieving targeted exon excision in the COL7A1 gene through a dual-RNA guide system. The biophysical properties of HPAE-EB were found to be efficient and cytocompatible in HEK293 cells, with a target genomic excision rate of 15-20%, but showed reduced efficiency in RDEB keratinocytes. However, delivery of CRISPR-Cas9 as a ribonucleoprotein complex increased targeted genomic excision to over 40%.
Article
Engineering, Biomedical
Nicholas Distasio, France Dierick, Talin Ebrahimian, Maryam Tabrizian, Stephanie Lehoux
Summary: This study designed and developed targeted nanoparticles (NP-VHPK) containing IL-10 DNA for atherosclerosis. The results showed that IL-10 can accumulate at atherosclerotic plaques after injection of NP-VHPK, leading to a decrease in local inflammation.
ACTA BIOMATERIALIA
(2022)
Review
Chemistry, Multidisciplinary
Marisa Thompson, Carmen Scholz
Summary: Poly(amino acid)s, built from natural amino acids, are biocompatible, biodegradable, and metabolizable, making them promising for biomedical applications. Highly branched polymers, such as dendrimers, have been studied for gene and drug delivery, with potential applications in antiviral compounds and nucleic acid delivery systems. However, despite over 40 years of research, they have not yet been widely adopted in clinical settings.
Article
Nanoscience & Nanotechnology
Jiahao Shi, Yuhe Zhang, Bin Ma, Haiyang Yong, Delu Che, Chaolan Pan, Wei He, Dezhong Zhou, Ming Li
Summary: A modular strategy was developed to manipulate the amphiphilicity of PAE/DNA polyplexes by synthesizing hydrophobic and hydrophilic modules and changing their ratio. Using this strategy, the polyplexes with the highest gene transfection efficiency and safety profile were identified.
ACS APPLIED MATERIALS & INTERFACES
(2023)
Review
Nutrition & Dietetics
Xiaonan Zhang, Mengxue Xia, Yingjie Wu, Fang Zhang
Summary: Retinopathy is a major cause of irreversible blindness and vision loss worldwide. Imbalanced nutrients, especially Branched-Chain Amino Acids (BCAAs), play important roles in the development and progression of retinal diseases. This review summarizes the changes in BCAA levels in retinopathy, especially in diabetic retinopathy and aging-related macular disease, as well as the genetics, functions, and mechanisms of BCAAs in the retina and other metabolic tissues. The aim of this review is to provide fundamental knowledge of BCAAs for further research on retina health.
Review
Medicine, Research & Experimental
Jiayu Zhang, Xiaomeng Cai, Rui Dou, Chen Guo, Jiaruo Tang, Yi Hu, Hanqing Chen, Jun Chen
Summary: This review provides a comprehensive overview of the synthesis and properties of poly(beta-amino) esters (PbAEs) and summarizes the progress of each type of PbAE for gene delivery. The review focuses on the rational design of PbAE structures, discusses the correlations between intrinsic structure and effect, and concludes with the applications and perspectives of PbAEs.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2023)
Article
Agronomy
Di Gong, Yang Bi, Yuanyuan Zong, Yongcai Li, Edward Sionov, Dov Prusky
Summary: The study revealed that infection with Penicillium expansum significantly increased the accumulation of amino acids in apple fruits, leading to enhanced biosynthesis of branched-chain volatile compounds.
POSTHARVEST BIOLOGY AND TECHNOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Chenfei Wang, Litao Sun, Qiuxia Li, Zhili Li, Chengyuan Xu, Xinyue Zhang, Jianjun Shi, Hao Zhou, Wenxin Wang, Dezhong Zhou
Summary: By using a stepwise precipitation strategy, highly branched poly(beta-amino ester)s (HPAEs) were fractionated, and it was found that the molecular weight (MW) significantly affects the transfection activity and cytotoxicity of HPAEs. Intermediate MW of HPAEs shows higher transfection efficiency and cell viability. Mechanistic studies reveal that the intermediate MW of HPAEs has stronger DNA binding affinity, leading to the formation of smaller polyplexes with more positive zeta potential. This study provides a simple strategy to fractionate HPAEs and offers new insights into the structure-property relationship for potential clinical translation in gene therapy.
CHINESE CHEMICAL LETTERS
(2023)
Review
Chemistry, Multidisciplinary
Jing Lyu, Yinghao Li, Zishan Li, Piotr Polanowski, Jeremiasz K. Jeszka, Krzysztof Matyjaszewski, Wenxin Wang
Summary: This article presents a minireview on the most important modelling techniques and their applications in free radical polymerization (FRP) and reversible-deactivation radical polymerization (RDRP) of multivinyl monomers (MVMs). The combination of experiments and modelling can provide valuable assets for polymer researchers, inspiring new thinking for future MVMs experiment optimization and product design.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Delu Che, Chenfei Wang, Zhili Li, Kaixuan Wang, Shuaiwei Sun, Xinyue Zhang, Yi Li, Zhengju Chen, Lei Guo, Yajing Hou, Dezhong Zhou, Songmei Geng
Summary: Suspension cells play a crucial role in many biological processes. However, introducing exogenous genes into suspension cells for gene regulation is challenging. By designing and synthesizing highly branched poly(ss-amino ester) (HPAE), we enhance the interactions of polyplexes with cellular membranes, resulting in improved gene transfection efficiency in mast cells (MCs) without cytotoxicity. This study establishes a reliable non-viral platform for efficient gene transfection of suspension cells.
CHINESE CHEMICAL LETTERS
(2023)
Article
Engineering, Biomedical
Xiaoyu Wang, Yuyang Zhou, Melissa Johnson, Cameron Milne, A. Sigen, Yening Li, Wenxin Wang, Nan Zhang, Qian Xu
Summary: In this study, aldehyde chitosan (CTS-CHO) was prepared through an oxidation reaction using chitosan and sodium periodate, and a chitosan-based hydrophilic and antibacterial coating was developed on the surface of poly(lactic acid) film. The results showed that the ultrasonic atomization-assisted LbL assembly CTS-CHO coating had great potential in improving the hydrophilicity and antibacterial activity of the PLA film, and it could also react with amino groups to release drugs, making it a promising alternative for biomedical applications.
JOURNAL OF FUNCTIONAL BIOMATERIALS
(2023)
Article
Engineering, Biomedical
Jing Zhang, Zhonglei He, Yinghao Li, Yu Shen, Guanfu Wu, Laura Power, Rijian Song, Ming Zeng, Xianqing Wang, Irene Lara Saez, A. Sigen, Qian Xu, James F. Curtin, Ziyi Yu, Wenxin Wang
Summary: Despite the great achievements of gene therapy in research and clinical translation, challenges such as limited control of drug pharmacokinetics and acute toxicity still persist. In this study, a gene therapy gel was formulated using polyplex nanoparticles and granular hydrogels, which showed controlled drug release, reduced toxicity, and improved transfection efficacy. The gel provides great convenience for storage, dosing, and administration, and represents a major advance in gene therapy formulations.
ACTA BIOMATERIALIA
(2023)
Article
Chemistry, Multidisciplinary
Ji Liu, James Garcia, Liam M. M. Leahy, Rijian Song, Daragh Mullarkey, Ban Fei, Adrian Dervan, Igor V. V. Shvets, Plamen Stamenov, Wenxin Wang, Fergal J. J. O'Brien, Jonathan N. N. Coleman, Valeria Nicolosi
Summary: Direct ink writing (DIW) is a viable 3D printing technology for custom production of functional conductive hydrogels. This study demonstrates a highly 3D printable PEDOT:PSS-based ink made from commercially accessible raw materials. The 3D-printed hydrogel exhibits high electrical conductivity, outstanding elasticity, stability in water, electromagnetic interference shielding, sensing capabilities, and biocompatibility, showing potential for implantable and tissue engineering applications. The fabrication strategy opens up new opportunities to create multifunctional hydrogels with custom features and expand the applications of hydrogel materials.
ADVANCED FUNCTIONAL MATERIALS
(2023)
Review
Chemistry, Multidisciplinary
Kolade Adebowale, Rick Liao, Vineeth Chandran Suja, Neha Kapate, Andrew Lu, Yongsheng Gao, Samir Mitragotri
Summary: Cell therapies have shown promise in treating previously incurable diseases, and the engineering of cell surfaces with various materials has emerged as a valuable tool to enhance their therapeutic performance. This review summarizes recent advances in decorating cell surfaces with nanoparticles, microparticles, and polymeric coatings, and highlights the benefits of surface modifications in protecting carrier cells, enhancing cell trafficking, and delivering therapeutic agents. While these technologies are still in the proof-of-concept stage, their promising efficacy from preclinical studies provides a strong foundation for future clinical translation, revolutionizing the field of cell therapies.
ADVANCED MATERIALS
(2023)
Review
Biochemistry & Molecular Biology
Xiaoyu Wang, Rijian Song, Melissa Johnson, A. Sigen, Pingping Shen, Nan Zhang, Irene Lara-Saez, Qian Xu, Wenxin Wang
Summary: Wound infections can lead to complications and slow down healing. Traditional antibiotic methods have resulted in antibiotic-resistant bacteria. Hydrogels with antimicrobial properties provide an alternative for reducing bacterial colonization and accelerating healing. Chitosan-based hydrogels have been extensively studied for infected wound treatment. This review summarizes their research progress, including fabrication methods, antibacterial mechanisms, performance, and wound healing efficacy, as well as current limitations and future trends.
MACROMOLECULAR BIOSCIENCE
(2023)
Article
Polymer Science
Zishan Li, Jing Lyu, Yinghao Li, Bei Qiu, Melissa Johnson, Hongyun Tai, Wenxin Wang
Summary: Well-defined polyacrylamide (PAM) was successfully synthesized via a one-pot and one-step aqueous Cu(0)-mediated reversible-deactivation radical polymerization (RDRP). Strong deactivation control is the key to the controllability of acrylamide (AM) RDRPs, which depends on the equilibria of polymerization and mutual conversion of different copper species. Using this kinetically controlled strategy, PAMs with narrow molecular weight distributions (MWDs) and varied molecular weights (M(w)s) were achieved.
Article
Polymer Science
Yinghao Li, Zhonglei He, Xianqing Wang, Zishan Li, Melissa Johnson, Ruth Foley, A. Sigen, Jing Lyu, Wenxin Wang
Summary: Poly(& beta;-amino ester)(PAE) has been developed as a key nonviralgene therapy vector, but its DNA delivery efficiency still lags behind viral vectors. In this work, highly branched PAEs (HPAEs) were investigated and it was found that the distribution of branch units (BUD) is a crucial factor for the transfection capability of HPAE. By optimizing BUD, a high-efficiency HPAE that surpasses commercial reagents can be generated.
Article
Polymer Science
Yinghao Li, Xianqing Wang, Zhonglei He, Zishan Li, Melissa Johnson, Bei Qiu, Rijian Song, A. Sigen, Irene Lara-Saez, Jing Lyu, Wenxin Wang
Summary: In this study, the effect of molecular weight components on gene delivery efficiency of highly branched poly(beta-amino ester) (HPAE) was investigated. It was found that removing small molecular weight portions from HPAE significantly enhanced its transfection performance. By applying a structural optimization strategy, a highly efficient HPAE gene delivery vector was developed, which opens up new opportunities for gene therapy applications.
Article
Biotechnology & Applied Microbiology
Yongsheng Gao, Mayumi Ikeda-Imafuku, Zongmin Zhao, Maithili Joshi, Samir Mitragotri
Summary: HAPPI is a polymer peptide-based hemostatic agent that selectively binds to activated platelets and injury sites, providing effective treatment for various lethal traumatic bleeding conditions.
BIOENGINEERING & TRANSLATIONAL MEDICINE
(2023)
Article
Nanoscience & Nanotechnology
Yinghao Li, Zhonglei He, A. Sigen, Xianqing Wang, Zishan Li, Melissa Johnson, Ruth Foley, Irene Lara Saez, Jing Lyu, Wenxin Wang
Summary: Gene therapy is a significant advancement in medicine, but the development of effective gene delivery vectors, especially polymer vectors, remains challenging. Limited understanding of polymer vector's internal structure hinders efforts to enhance efficiency. This study investigates the impact of polymer structure on gene delivery using poly(beta-amino ester) (PAE), and reveals the distinct characteristics and synergistic effects of individual polymer components. Artificial intelligence analysis is employed to decipher the relationship between polymer component distribution (PCD) and gene transfection performance, leading to the development of highly efficient polymer vectors that outperform current commercial reagents.
ACS APPLIED MATERIALS & INTERFACES
(2023)
Review
Biotechnology & Applied Microbiology
Yongsheng Gao, Maithili Joshi, Zongmin Zhao, Samir Mitragotri
Summary: PEGylation, the covalent attachment of polyethylene glycol (PEG) to therapeutic agents, is an established drug delivery approach that improves the pharmacokinetics and pharmacodynamics of drugs. PEGylation improves solubility, circulation time, and reduces immunogenicity of drugs with minimal undesirable properties. PEGylation has been successfully applied to various therapeutic modalities and has resulted in numerous PEGylated drugs currently in clinical use.
BIOENGINEERING & TRANSLATIONAL MEDICINE
(2023)
Article
Materials Science, Multidisciplinary
Xiaoyu Wang, Melissa Johnson, Nan Zhang, Pingping Shen, Lizhu Yang, Cameron Milne, Irene Lara-Saez, Rijian Song, A. Sigen, Wenxin Wang
Summary: Compared with traditional drug delivery systems, stimuli-responsive injectable hydrogels that undergo sol-gel transition in response to external stimuli demonstrate significant advantages in on-demand drug release. In this study, a simplified one-step method was developed to prepare a stimuli-responsive chitosan-based injectable hydrogel using dynamic Schiff's base reaction. The hydrogel exhibited excellent stimuli-responsive properties and showed potential for on-demand drug release in response to pH stimuli.
MATERIALS ADVANCES
(2023)
