Synthesis and functionalization of dendritic polyglycerol-based nanogels: application in T cell activation

Reisbeck, Felix; Wedepohl, Stefanie; Dimde, Mathias; Schmitt, Ann‐Cathrin; Dernedde, Jens; Álvaro-Benito, Miguel; Freund, Christian; Haag, Rainer

doi:10.1039/d1tb02144c

Cited by 9 publications

(9 citation statements)

References 51 publications

(51 reference statements)

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“…171,172 Recently, Haag et al designed a dendritic polyglycerol-based nanogel through inverse nanoprecipitation for the delivery of aCD3 and aCD28 to activate T cells. 173 This nanogel can induce greater activation of T cells at lower dosages compared with conventional compounds. More importantly, this nanogel may represent a promising candidate for the delivery of a variety of antibodies due to the mild reaction conditions and high universality.…”

Section: Nanogel For Targeted Antibody Deliverymentioning

confidence: 99%

Bioengineered nanogels for cancer immunotherapy

Liu

et al. 2022

Chem. Soc. Rev.

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Section: Nanogel For Targeted Antibody Deliverymentioning

confidence: 99%

Bioengineered nanogels for cancer immunotherapy

Liu

et al. 2022

Chem. Soc. Rev.

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“…In aqueous media, these groups exist in a dynamic equilibrium between a hydrophobic trigonal-planar form and an ionized hydrophilic tetrahedral form. In presence of di- [127] Copyright 2022, The Authors, published by the Royal Society of Chemistry.…”

Section: Selective Factors: Presence Of Affinity Bindersmentioning

confidence: 99%

Rational Design and Development of Polymeric Nanogels as Protein Carriers

López‐Iglesias

Klinger

2023

Macromolecular Bioscience

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Proteins have gained significant attention as potential therapeutic agents owing to their high specificity and reduced toxicity. Nevertheless, their clinical utility is hindered by inherent challenges associated with stability during storage and after in vivo administration. To overcome these limitations, polymeric nanogels (NGs) have emerged as promising carriers. These colloidal systems are capable of efficient encapsulation and stabilization of protein cargoes while improving their bioavailability and targeted delivery. The design of such delivery systems requires a comprehensive understanding of how the synthesis and formulation processes affect the final performance of the protein. This review highlights critical aspects involved in the development of NGs for protein delivery, with specific emphasis on loading strategies and evaluation techniques. For example, factors influencing loading efficiency and release kinetics are discussed, along with strategies to optimize protein encapsulation through protein‐carrier interactions to achieve the desired therapeutic outcomes. The discussion is based on recent literature examples and aims to provide valuable insights for researchers working towards the advancement of protein‐based therapeutics.This article is protected by copyright. All rights reserved

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“…NGs are particularly interesting due to their simple surfactant-free fabrication, high protein loading capacity, and stability under physiological conditions. − Their cross-linked three-dimensional network structure offers a variety of tunable parameters to address specific receptors and ensure targeted protein release. Click-type reactions such as the strain-promoted azide-alkyne cycloaddition (SPAAC) and the inverse electron-demand Diels–Alder cyclization (iEDDA) have emerged as a promising cross-linking strategy for macromonomers to form NGs. , They offer fast reaction kinetics, can be carried out under cell- and organism-friendly conditions, and do not possess cross-reactivity with other functional groups from the biological environment. Furthermore, modification of the reactive cross-linking moieties allows the integration of chemical groups with biodegradable bonds, such as acetals, disulfides, or hydrazones, that can be addressed by physiological stimuli.…”

Section: Introductionmentioning

confidence: 99%

“…Click-type reactions such as the strainpromoted azide-alkyne cycloaddition (SPAAC) and the inverse electron-demand Diels−Alder cyclization (iEDDA) have emerged as a promising cross-linking strategy for macromonomers to form NGs. 43,44 They offer fast reaction kinetics, can be carried out under cell-and organism-friendly conditions, and do not possess cross-reactivity with other functional groups from the biological environment. Furthermore, modification of the reactive cross-linking moieties allows the integration of chemical groups with biodegradable bonds, such as acetals, 36 disulfides, 45 or hydrazones, 46 that can be addressed by physiological stimuli.…”

Section: ■ Introductionmentioning

confidence: 99%

pH-Degradable Polyglycerol-Based Nanogels for Intracellular Protein Delivery

Schötz,

Goerisch,

Mavroskoufis

et al. 2023

ACS Appl. Nano Mater.

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The growing interest in therapeutic proteins for biomedical applications is still limited by their tendency to degrade and undergo opsonization when exposed to physiological conditions. To protect them from external stimuli and mask their immunogenic sites, poly(ethylene glycol) can be covalently attached to the biomolecules. While this process requires a chemical modification of the original structure and can cause immunogenic reactions, therapeutic proteins can be masked by noncovalent encapsulation into nanocarriers such as nanogels (NGs). Here, we present the synthesis of four new pH-degradable NGs and evaluate their potential to serve as a cytochrome C (CC) delivery platform. Our surfactant-free encapsulation protocol for CC relies on forming NGs through inverse nanoprecipitation using inverse electron-demand Diels−Alder cyclizations (iEDDA) between methyl tetrazines and norbornenes. We compare an aliphatic acetal with different benzacetals and evaluate the substituents' influence on the NGs' cleavability and the subsequent intracellular release of CC. Introducing an aromatic π-system beside the acetal framework increased the NG stability against buffer ions and shifted the acetal hydrolysis to the desired lyso-and endosomal pH values. Increasing the degree of substitution in the meta-position with methoxy groups, smaller NGs and more acid-stable acetals were obtained. The BA(OMe)-NGs emerged as the most promising candidate, exhibiting great stability at pH 7.4 and acetal hydrolysis at pH ≤ 6.5 without aggregation. Remarkably, this system released up to 60% of the loaded CC after 96 hours of incubation at endosomal pH values, causing apoptosis of McF7 cells with IC50 values of 8.25 μM.

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Synthesis and functionalization of dendritic polyglycerol-based nanogels: application in T cell activation

Abstract: The concept of multivalency finds various applications in the fields of chemistry and biology, relying on the principle that multiple weak interactions can lead to strong adhesive forces. Polymeric carriers...

Cited by 9 publications

References 51 publications

Bioengineered nanogels for cancer immunotherapy

Bioengineered nanogels for cancer immunotherapy

Rational Design and Development of Polymeric Nanogels as Protein Carriers

pH-Degradable Polyglycerol-Based Nanogels for Intracellular Protein Delivery

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