bims-novged Biomed News
on Non-viral vectors for gene delivery
Issue of 2022–07–10
fourteen papers selected by
the Merkel lab, Ludwig-Maximilians University
  1. Amphiphilic Dendrimer Vectors for RNA Delivery: State-of-the-Art and Future Perspective.
  2. Ionizable Lipid Nanoparticle-Mediated Delivery of Plasmid DNA in Cardiomyocytes.
  3. Nebulization of siRNA for inhalation therapy based on a microfluidic surface acoustic wave platform.
  4. The role of lipid components in lipid nanoparticles for vaccines and gene therapy.
  5. [Application of nanoparticles in CRISPR/Cas9-based gene therapy].
  6. Lipid nanoparticles to silence androgen receptor variants for prostate cancer therapy.
  7. An optimized ionizable cationic lipid for brain tumor-targeted siRNA delivery and glioblastoma immunotherapy.
  8. Lipid nanoparticles in the development of mRNA vaccines for COVID-19.
  9. Suppression of SARS-CoV-2 Replication with Stabilized and Click-Chemistry Modified siRNAs.
  10. Therapeutic in vivo delivery of gene editing agents.
  11. Mucus-penetrating nanoparticles based on chitosan grafted with various non-ionic polymers: Synthesis, structural characterisation and diffusion studies.
  12. Delivering an mRNA vaccine using a lymphatic drug delivery device improves humoral and cellular immunity against SARS-CoV-2.
  13. Polymeric Amines Induce Nitric Oxide Release from S-Nitrosothiols.
  14. Zwitterionic Polypeptoids: A Promising Class of Antifouling Bioinspired Materials.
  1. Acc Mater Res. 2022 May 27. 3(5): 484-497
    Amphiphilic Dendrimer Vectors for RNA Delivery: State-of-the-Art and Future Perspective.
    Jiaxuan Chen, Dandan Zhu, Xiaoxuan Liu, Ling Peng.
      Dendrimers, a special family of polymers, are particularly promising materials for various biomedical applications by virtue of their well-defined dendritic structure and cooperative multivalency. Specifically, in this Account, we present state-of-the-art amphiphilic dendrimers for nucleic acid delivery. Ribonucleic acid (RNA) molecules are fast becoming an important drug modality, particularly since the recent success of mRNA vaccines against COVID-19. Notably, RNA therapeutics offer the unique opportunity to treat diseases at the gene level and address "undruggable" targets. However, RNA therapeutics are not stable and have poor bioavailability, imposing the need for their protection and safe delivery by vectors to the sites-of-action to allow the desired therapeutic effects. Currently, the two most advanced nonviral vectors are based on lipids and polymers, with lipid vectors primarily exploiting the membrane-fusion mechanism and polymer vectors mainly endocytosis-mediated delivery. Notably, only lipid vectors have been advanced through to their clinical use in the delivery of, for example, the first siRNA drug and the first mRNA vaccine. The success of lipid vectors for RNA delivery has motivated research for further innovative materials as delivery vectors. Specifically, we have pioneered lipid/dendrimer conjugates, referred to as amphiphilic dendrimers, for siRNA delivery with the view to harnessing the delivery advantages of both lipid and polymer vectors while enjoying the unique structural features of dendrimers. These amphiphilic dendrimer vectors are lipid/dendrimer hybrids and are thus able to mimic lipid vectors and exploit membrane-fusion-mediated delivery, while simultaneously retaining the multivalent properties of polymer vectors that allow endocytosis-based delivery. In addition, they have precisely controllable and stable nanosized chemical structures and offer nanotechnology-based delivery. Effective amphiphilic dendrimer vectors share two important elements: chemical hydrophilic entities to bind RNA and RNA complex-stabilizing hydrophobicity. These two combined features allow the encapsulation of RNA within a stable complex before its release into the cytosol following endocytosis. This hydrophilic/hydrophobic balance permitted by the structural features of amphiphilic dendrimers plays a determining role in RNA delivery success. In this Account, we provide a conceptual overview of this exciting field with the latest breakthroughs and key advances in the design of amphiphilic dendrimers for the delivery of siRNA and mRNA. Specifically, we start with a short introduction to siRNA- and mRNA-based therapeutics and their delivery challenges. We then outline the pioneering and representative studies on amphiphilic dendrimer vectors to highlight their historical development and promising features that offer to facilitate the once challenging RNA delivery. We conclude by offering perspectives for the future of amphiphilic dendrimer vectors for nucleic acid delivery in general.
    DOI:  https://doi.org/10.1021/accountsmr.1c00272
  2. Int J Nanomedicine. 2022 ;17 2865-2881
    Ionizable Lipid Nanoparticle-Mediated Delivery of Plasmid DNA in Cardiomyocytes.
    Sérgio Scalzo, Anderson K Santos, Heloísa A S Ferreira, Pedro A Costa, Pedro H D M Prazeres, Natália J A da Silva, Lays C Guimarães, Mário de Morais E Silva, Marco T R Rodrigues Alves, Celso T R Viana, Itamar C G Jesus, Alice P Rodrigues, Alexander Birbrair, Anderson O Lobo, Frederic Frezard, Michael J Mitchell, Silvia Guatimosim, Pedro Pires Goulart Guimaraes.
       Introduction: Gene therapy is a promising approach to be applied in cardiac regeneration after myocardial infarction and gene correction for inherited cardiomyopathies. However, cardiomyocytes are crucial cell types that are considered hard-to-transfect. The entrapment of nucleic acids in non-viral vectors, such as lipid nanoparticles (LNPs), is an attractive approach for safe and effective delivery.
    Methods: Here, a mini-library of engineered LNPs was developed for pDNA delivery in cardiomyocytes. LNPs were characterized and screened for pDNA delivery in cardiomyocytes and identified a lead LNP formulation with enhanced transfection efficiency.
    Results: By varying lipid molar ratios, the LNP formulation was optimized to deliver pDNA in cardiomyocytes with enhanced gene expression in vitro and in vivo, with negligible toxicity. In vitro, our lead LNP was able to reach a gene expression greater than 80%. The in vivo treatment with lead LNPs induced a twofold increase in GFP expression in heart tissue compared to control. In addition, levels of circulating myeloid cells and inflammatory cytokines remained without significant changes in the heart after LNP treatment. It was also demonstrated that cardiac cell function was not affected after LNP treatment.
    Conclusion: Collectively, our results highlight the potential of LNPs as an efficient delivery vector for pDNA to cardiomyocytes. This study suggests that LNPs hold promise to improve gene therapy for treatment of cardiovascular disease.
    Keywords:  cardiomyocytes; heart; ionizable lipids; lipid nanoparticles; pDNA delivery
    DOI:  https://doi.org/10.2147/IJN.S366962
  3. Ultrason Sonochem. 2022 Jun 30. pii: S1350-4177(22)00183-3. [Epub ahead of print]88 106088
    Nebulization of siRNA for inhalation therapy based on a microfluidic surface acoustic wave platform.
    Christina Cortez-Jugo, Sarah Masoumi, Peggy P Y Chan, James Friend, Leslie Yeo.
      The local delivery of therapeutic small interfering RNA or siRNA to the lungs has the potential to improve the prognosis for patients suffering debilitating lung diseases. Recent advances in materials science have been aimed at addressing delivery challenges including biodistribution, bioavailability and cell internalization, but an equally important challenge to overcome is the development of an inhalation device that can deliver the siRNA effectively to the lung, without degrading the therapeutic itself. Here, we report the nebulization of siRNA, either naked siRNA or complexed with polyethyleneimine (PEI) or a commercial transfection agent, using a miniaturizable acoustomicrofluidic nebulization device. The siRNA solution could be nebulised without significant degradation into an aerosol mist with tunable mean aerodynamic diameters of approximately 3 µm, which is appropriate for deep lung deposition via inhalation. The nebulized siRNA was tested for its stability, as well as its toxicity and gene silencing properties using the mammalian lung carcinoma cell line A549, which demonstrated that the gene silencing capability of siRNA is retained after nebulization. This highlights the potential application of the acoustomicrofluidic device for the delivery of efficacious siRNA via inhalation, either for systemic delivery via the alveolar epithelium or local therapeutic delivery to the lung.
    Keywords:  Lung delivery; Nanoparticles; Nebulizer; Surface acoustic waves; siRNA
    DOI:  https://doi.org/10.1016/j.ultsonch.2022.106088
  4. Adv Drug Deliv Rev. 2022 Jul 01. pii: S0169-409X(22)00306-4. [Epub ahead of print] 114416
    The role of lipid components in lipid nanoparticles for vaccines and gene therapy.
    Camilla Hald Albertsen, Jayesh Kulkarni, Dominik Witzigmann, Marianne Lind, Karsten Petersson, Jens B Simonsen.
      Lipid nanoparticles (LNPs) play a key role in mRNA vaccines against COVID-19. In addition, many preclinical and clinical studies, including the siRNA-LNP product, Onpattro®, highlight that LNPs unlock the potential of nucleic acid-based therapies and vaccines. To understand how this 'key' works, we need to learn about the building blocks that constitute LNPs. In this review, we discuss what each lipid component adds to the LNP delivery platform in terms of size, structure, stability, apparent pKa, nucleic acid encapsulation efficiency, cellular uptake, and endosomal escape. To explore this, we present findings from the liposome field and from landmark and recent articles in the LNP literature. We also discuss challenges and strategies related to in vitro/in vivo studies of LNPs based on fluorescence readouts, immunogenicity/reactogenicity, and LNP delivery beyond the liver. How these fundamental challenges are pursued, including what lipid components are added and combined, will likely determine the scope of LNP-based gene therapies and vaccines for treating various diseases.
    Keywords:  Drug Delivery; Helper lipid; Ionizable lipid; LNP; Lipid nanoparticles; Nucleic Acid; PEGylated lipid; Physicochemical Properties; Targeting; pK(a)
    DOI:  https://doi.org/10.1016/j.addr.2022.114416
  5. Sheng Wu Gong Cheng Xue Bao. 2022 Jun 25. 38(6): 2087-2104
    [Application of nanoparticles in CRISPR/Cas9-based gene therapy].
    Yue Ma, Li Deng, Shangang Li.
      CRISPR/Cas9 is a cutting-edge gene-editing technology that has emerged as a promising tool for gene therapy. Nevertheless, the safe and efficient delivery of CRISPR/Cas9 is still an urgent issue in clinical application. Nanoparticles, such as lipid-based nanoparticles, polymer nanoparticles, gold nanoparticles, and biofilm nanoparticles, are expected to bring new opportunities for CRISPR/Cas9-based gene therapy because of their biocompatibility, safety and designability. This review briefly introduced the characteristics of nanoparticles and the development of CRISPR/Cas9 in gene therapy. Moreover, the application of nanoparticles in the delivery of different forms of CRISPR/Cas9 were elaborated. Finally, the challenges and safety of nanoparticle-based gene therapy were discussed.
    Keywords:  CRISPR/Cas9; gene therapy; nanoparticles; non-viral vector
    DOI:  https://doi.org/10.13345/j.cjb.210739
  6. J Control Release. 2022 Jun 30. pii: S0168-3659(22)00393-5. [Epub ahead of print]
    Lipid nanoparticles to silence androgen receptor variants for prostate cancer therapy.
    Joslyn Quick, Nancy Dos Santos, Miffy H Y Cheng, Nisha Chander, Cedric A Brimacombe, Jayesh Kulkarni, Roy van der Meel, Yuen Yi C Tam, Dominik Witzigmann, Pieter R Cullis.
      Advanced-stage prostate cancer remains an incurable disease with poor patient prognosis. There is an unmet clinical need to target androgen receptor (AR) splice variants, which are key drivers of the disease. Some AR splice variants are insensitive to conventional hormonal or androgen deprivation therapy due to loss of the androgen ligand binding domain at the C-terminus and are constitutively active. Here we explore the use of RNA interference (RNAi) to target a universally conserved region of all AR splice variants for cleavage and degradation, thereby eliminating protein level resistance mechanisms. To this end, we tested five siRNA sequences designed against exon 1 of the AR mRNA and identified several that induced potent knockdown of full-length and truncated variant ARs in the 22Rv1 human prostate cancer cell line. We then demonstrated that 2'O methyl modification of the top candidate siRNA (siARvm) enhanced AR and AR-V7 mRNA silencing potency in both 22Rv1 and LNCaP cells, which represent two different prostate cancer models. For downstream in vivo delivery, we formulated siARvm-LNPs and functionally validated these in vitro by demonstrating knockdown of AR and AR-V7 mRNA in prostate cancer cells and loss of AR-mediated transcriptional activation of the PSA gene in both cell lines following treatment. We also observed that siARvm-LNP induced cell viability inhibition was more potent compared to LNP containing siRNA targeting full-length AR mRNA (siARfl-LNP) in 22Rv1 cells as their proliferation is more dependent on AR splice variants than LNCaP and PC3 cells. The in vivo biodistribution of siARvm-LNPs was determined in 22Rv1 tumor-bearing mice by incorporating 14C-radiolabelled DSPC in LNP formulation, and we observed a 4.4% ID/g tumor accumulation following intravenous administration. Finally, treatment of 22Rv1 tumor bearing mice with siARvm-LNP resulted in significant tumor growth inhibition and survival benefit compared to siARfl-LNP or the siLUC-LNP control. To best of our knowledge, this is the first report demonstrating therapeutic effects of LNP-siRNA targeting AR splice variants in prostate cancer.
    Keywords:  Androgen receptor; Gene therapy; Lipid nanoparticle; Prostate cancer; Splice variant; siRNA
    DOI:  https://doi.org/10.1016/j.jconrel.2022.06.051
  7. Biomaterials. 2022 Jun 22. pii: S0142-9612(22)00285-X. [Epub ahead of print]287 121645
    An optimized ionizable cationic lipid for brain tumor-targeted siRNA delivery and glioblastoma immunotherapy.
    Shuhan Liu, Ji Liu, Haisong Li, Kuirong Mao, Haorui Wang, Xiandi Meng, Jialiang Wang, Chenxi Wu, Hongmei Chen, Xin Wang, Xiuxiu Cong, Yue Hou, Ye Wang, Ming Wang, Yong-Guang Yang, Tianmeng Sun.
      Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor with a high mortality rate. Immunotherapy has achieved promising clinical results in multiple cancers, but shows unsatisfactory outcome in GBM patients, and poor drug delivery across the blood-brain barrier (BBB) is believed to be one of the main limitations that hinder the therapeutic efficacy of drugs. Herein, a new cationic lipid nanoparticle (LNP) that can efficiently deliver siRNA across BBB and target mouse brain is prepared for modulating the tumor microenvironment for GBM immunotherapy. By designing and screening cationic LNPs with different ionizable amine headgroups, a lipid (named as BAMPA-O16B) is identified with an optimal acid dissociation constant (pKa) that significantly enhances the cellular uptake and endosomal escape of siRNA lipoplex in mouse GBM cells. Importantly, BAMPA-O16B/siRNA lipoplex is highly effective to deliver siRNA against CD47 and PD-L1 across the BBB into cranial GBM in mice, and downregulate target gene expression in the tumor, resulting in synergistically activating a T cell-dependent antitumor immunity in orthotopic GBM. Collectively, this study offers an effective strategy for brain targeted siRNA delivery and gene silencing by optimizing the physicochemical property of LNPs. The effectiveness of modulating immune environment of GBM could further be expanded for potential treatment of other brain tumors.
    Keywords:  Blood-brain barrier; Cationic lipid nanoparticle; Glioblastoma multiforme; Tumor immunotherapy; Tumor microenvironment
    DOI:  https://doi.org/10.1016/j.biomaterials.2022.121645
  8. J Drug Deliv Sci Technol. 2022 Aug;74 103553
    Lipid nanoparticles in the development of mRNA vaccines for COVID-19.
    Barnabas Wilson, Kannoth Mukundan Geetha.
      Coronavirus disease (COVID-19) was first reported in December 2019, Hubei Province, China. As on 9th December 2021, severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has affected 266018810 people worldwide with 5265092 deaths. The outbreak of COVID-19 pandemic has caused severe public health crisis across the world. Nucleic acids have been emerging as potential drugs to treat a variety of diseases. Lipid nanoparticles (LNPs) have great potential to deliver nucleic acids including mRNAs. The two mRNA-based vaccines namely the BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) have been given emergency use authorization (EUA) by the US-FDA to prevent SARS-CoV-2 caused COVID-19 and the vaccines were developed using LNPs. This article focuses on the potential application of LNPs in the development and delivery of mRNA vaccines for COVID-19.
    Keywords:  BNT162b2; COVID-19; Lipid nanoparticles; Nanotechnology; Vaccines; mRNA; mRNA-1273
    DOI:  https://doi.org/10.1016/j.jddst.2022.103553
  9. Angew Chem Int Ed Engl. 2022 Jul 08.
    Suppression of SARS-CoV-2 Replication with Stabilized and Click-Chemistry Modified siRNAs.
    Franziska R Traube, Marcel Stern, Annika J Tölke, Martina Rudelius, Ernesto Mejías-Pérez, Nada Raddaoui, Beate M Kümmerer, Céline Douat, Filipp Streshnev, Manuel Albanese, Paul R Wratil, Yasmin V Gärtner, Milda Nainytė, Grazia Giorgio, Stylianos Michalakis, Sabine Schneider, Hendrick Streeck, Markus Müller, Oliver T Keppler, Thomas Carell.
      TThe emergence of more transmissible or aggressive variants of SARS-CoV-2 requires the development of antiviral medication that is quickly adjustable to evolving viral escape mutations. Here we report the synthesis of chemically stabilized small interfering RNA (siRNA) against SARS-CoV-2. The siRNA can be further modified with receptor ligands such as peptides using Cu(I)-catalysed click-chemistry. We demonstrate that optimized siRNAs can reduce viral loads and virus-induced cytotoxicity by up to five orders of magnitude in cell lines challenged with SARS-CoV-2. Furthermore, we show that an ACE2-binding peptide-conjugated siRNA is able to reduce virus replication and virus-induced apoptosis in 3D mucociliary lung microtissues. The adjustment of the siRNA sequence allows a rapid adaptation of their antiviral activity against different variants of concern. The ability to conjugate the siRNA via click-chemistry to receptor ligands facilitates the construction of targeted siRNAs for a flexible antiviral defence strategy.
    Keywords:  Corona pandemic; SARS-CoV-2; antiviral compounds; peptide RNA conjugates; siRNA
    DOI:  https://doi.org/10.1002/anie.202204556
  10. Cell. 2022 Jun 28. pii: S0092-8674(22)00395-6. [Epub ahead of print]
    Therapeutic in vivo delivery of gene editing agents.
    Aditya Raguram, Samagya Banskota, David R Liu.
      In vivo gene editing therapies offer the potential to treat the root causes of many genetic diseases. Realizing the promise of therapeutic in vivo gene editing requires the ability to safely and efficiently deliver gene editing agents to relevant organs and tissues in vivo. Here, we review current delivery technologies that have been used to enable therapeutic in vivo gene editing, including viral vectors, lipid nanoparticles, and virus-like particles. Since no single delivery modality is likely to be appropriate for every possible application, we compare the benefits and drawbacks of each method and highlight opportunities for future improvements.
    DOI:  https://doi.org/10.1016/j.cell.2022.03.045
  11. J Colloid Interface Sci. 2022 Jun 27. pii: S0021-9797(22)01116-X. [Epub ahead of print]626 251-264
    Mucus-penetrating nanoparticles based on chitosan grafted with various non-ionic polymers: Synthesis, structural characterisation and diffusion studies.
    Twana Mohammed M Ways, Sergey K Filippov, Samarendra Maji, Mathias Glassner, Michal Cegłowski, Richard Hoogenboom, Stephen King, Wing Man Lau, Vitaliy V Khutoryanskiy.
      Transmucosal administration offers numerous advantages for drug delivery as it usually helps to avoid first pass metabolism, provides rapid onset of action, and is a non-invasive route. Mucosal surfaces are covered by a viscoelastic mucus gel layer which acts as a protective barrier preventing the entrance of harmful substances into the human tissues. This function of mucus also inhibits the diffusion of drugs and nano-formulations and can result in a significant reduction of their efficacy. The design of mucus-penetrating nanoparticles can overcome the barrier function of mucus which may lead to better therapeutic outcomes. In this study, chitosan was chemically modified by grafting short chains of poly(ethylene glycol), poly(2-hydroxyethyl acrylate), poly(2-ethyl-2-oxazoline), or poly(N-vinyl pyrrolidone) and the resulting chitosan derivatives were used to prepare nanoparticles using an ionic gelation method with sodium tripolyphosphate. These nanoparticles were characterised using dynamic light scattering, transmission electron microscopy, small-angle neutron scattering and nanoparticle tracking analysis. Small-angle neutron scattering data revealed the presence of a large amount of water inside these nanoparticles and lack of a heterogeneous internal structure. The nanogel model with low crosslinking density is suggested as the most feasible model to describe the structure of these nanoparticles. The studies of the behaviour of these nanoparticles in bovine submaxillary mucin solutions and their penetration into sheep nasal mucosa indicated greater diffusivity of modified chitosan nanoparticles compared to unmodified chitosan nanoparticles with the best results achieved for the chitosan grafted with poly(N-vinyl pyrrolidone).
    Keywords:  Chitosan; Diffusion; Drug delivery; Mucus penetration; Nanoparticles
    DOI:  https://doi.org/10.1016/j.jcis.2022.06.126
  12. J Mol Cell Biol. 2022 Jul 08. pii: mjac041. [Epub ahead of print]
    Delivering an mRNA vaccine using a lymphatic drug delivery device improves humoral and cellular immunity against SARS-CoV-2.
    Runqiang Chen, Hui Xie, Sahba Khorsandzadeh, Madison Smith, Namir Shaabani, Qidong Hu, Xiaoxuan Lyu, Hua Wang, Wan-Lin Lim, Haotian Sun, Henry Ji, Brian Cooley, Russell Ross, David M Francis.
      The exploration and identification of safe and effective vaccines for the SARS-CoV-2 pandemic has captured the world's attention and remains an ongoing issue due to concerns of balancing protection against emerging variants of concern (VoCs) while also generating long lasting immunity. Here, we report the synthesis of a novel messenger ribonucleic acid encoding the spike protein in a lipid nanoparticle formulation (STI-7264) that generates robust humoral and cellular immunity following immunization of C57Bl6 mice. In an effort to improve immunity, a clinically-focused lymphatic drug delivery device (MuVaxx) was engineered to modulate immune cells at the injection site (epidermis and dermis) and draining lymph node (LN) and tested to measure adaptive immunity. Using MuVaxx, immune responses were elicited and maintained at a 10-fold dose reduction compared to traditional intramuscular (IM) administration as measured by anti-spike antibodies, cytokine-producing CD8 T cells, neutralizing antibodies against the Washington (wild type) strain and South African (Beta) variants, and LN-resident spike-specific memory B cells. Remarkably, a 4-fold elevated T cell response was observed in MuVaxx administered vaccination compared to that of IM administered vaccination. Thus, these data support further investigation into STI-7264 and lymphatics-mediated delivery using MuVaxx for SARS-CoV-2 and VoC vaccines.
    Keywords:  COVID-19; drug delivery; lymph nodes; lymphatics; vaccines
    DOI:  https://doi.org/10.1093/jmcb/mjac041
  13. Small. 2022 Jul 05. e2200502
    Polymeric Amines Induce Nitric Oxide Release from S-Nitrosothiols.
    Zijie Luo, Gervase Ng, Yingzhu Zhou, Cyrille Boyer, Rona Chandrawati.
      Catalytic generation of nitric oxide (NO) from NO donors by nanomaterials has enabled prolonged NO delivery for various biomedical applications, but this approach requires laborious synthesis routes. In this study, a new class of materials, that is, polymeric amines including polyethyleneimine (PEI), poly-L-lysine, and poly(allylamine hydrochloride), is discovered to induce NO generation from S-nitrosothiols (RSNOs) at physiological conditions. Controlled NO generation can be readily achieved by tuning the concentration of the NO donors (RSNOs) and polymers, and the type and molecular weight of the polymers. Importantly, the mechanism of NO generation by these polymers is deciphered to be attributed to the nucleophilic reaction between primary amines on polymers and the SNO groups of RSNOs. The NO-releasing feature of the polymers can be integrated into a suite of materials, for example, simply by embedding PEI into poly(vinyl alcohol) (PVA) hydrogels. The functionality of the PVA/PEI hydrogels is demonstrated for Pseudomonas aeruginosa biofilm prevention with a ≈4 log reduction within 6 h. As NO has potential therapeutic implications in various diseases, the identification of polymeric amines to induce NO release will open new opportunities in NO-generating biomaterials for antibacterial, antiviral, anticancer, antithrombotic, and wound healing applications.
    Keywords:  S-nitrosoglutathiones; S-nitrosothiols; nitric oxide; polymers
    DOI:  https://doi.org/10.1002/smll.202200502
  14. Materials (Basel). 2022 Jun 26. pii: 4498. [Epub ahead of print]15(13):
    Zwitterionic Polypeptoids: A Promising Class of Antifouling Bioinspired Materials.
    Jian Ding, Xiangmin Ding, Jing Sun.
      Biofouling caused by protein adsorption and microbial colonization remains a great challenge in many applications. In this work, we synthesized a new type of zwitterionic polypeptoid containing carboxybetaine (CB) moieties (PeptoidCB) through thiol-ene chemistry of poly(N-allylglycine) (PNAG). The zwitterionic antifouling hydrogel was subsequently prepared by co-mixing PeptoidCB with agarose, which exhibited excellent resistance to non-specific protein adsorption and bacterial adhesion. Further, PeptoidCB-modified block copolypeptoids with amphiphilic structure were synthesized to form nanoparticles in an aqueous solution with neglected protein adsorption. The ability of PeptoidCB to resist non-specific protein adsorption and bacterial adhesion makes it a promising candidate for biomedical and industrial applications.
    Keywords:  antifouling hydrogel; nanoparticle; polypeptoid; ring-opening polymerization; zwitterionic polymer
    DOI:  https://doi.org/10.3390/ma15134498
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