Bisphosphonate-loaded nanogels attentuate liver fibrosis by repolarization of M2-type macrophages

Kaps, Leonard; Huppertsberg, Anne; Choteschovsky, Niklas; Klefenz, Adrian; Durak, Feyza; Schoers, Barbara; Diken, Mustafa; Eichler, Emma; Rosigkeit, Sebastian; Schmitt, Sascha; Leps, Christian; Förster, Friedrich; Bockamp, Ernesto; Degeest, Bruno; Marini, Federico; Koynov, Kaloian; Schuppan, Detlef; Nuhn, Lutz

doi:10.1016/s0168-8278(22)01257-0

Cited by 4 publications

(2 citation statements)

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“…The polymerization of drug-based monomers represents a facile and precise method for obtaining well-defined polymeric prodrug amphiphiles. [12] As the concentration of glutathione (GSH) inside tumor cells (1-10 mM) is 1000-fold higher than that in normal cells, we synthesized an IMQ-related monomer by caging the C4 amine with a self-immolative disulfide linker that is stable in blood. [13] Reversible addition-fragmentation chain transfer (RAFT) polymerization was used to polymerize these monomers to fabricate a nanosized delivery system.…”

Section: Introductionmentioning

confidence: 99%

Tumor‐Selective Activation of Toll‐Like Receptor 7/8 Agonist Nano‐Immunomodulator Generates Safe Anti‐Tumor Immune Responses upon Systemic Administration

Hao

et al. 2022

Angew Chem Int Ed

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Agonists of innate pattern recognition receptors such as toll-like receptors (TLRs) prime adaptive anti-tumor immunity and hold promise for cancer immunotherapy. However, small-molecule TLR agonists cause immune-related adverse effects (irAEs) after systemic administration. Herein, we report a polymeric nano-immunomodulator (cN@SS-IMQ) that is inactive until it is selectively metabolized to an active immunostimulant within the tumor. cN@SS-IMQ was obtained via self-assembly of a cyclo(Arg-Gly-Asp-D-Phe-Lys)modified amphiphilic copolymeric prodrug. Upon systemic administration, cN@SS-IMQ preferentially accumulated at tumor sites and responded to high intracellular glutathione levels to release native imidazoquinolines for dendritic cell maturation, thereby enhancing the infiltration of T lymphocytes. Collec-

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Section: Introductionmentioning

confidence: 99%

Tumor‐Selective Activation of Toll‐Like Receptor 7/8 Agonist Nano‐Immunomodulator Generates Safe Anti‐Tumor Immune Responses upon Systemic Administration

Hao

et al. 2022

Angew Chem Int Ed

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“…[11][12][13][14][15][16][17][18][19] Nanogels can be prepared using various methods including the formation of chemically or physically crosslinked selfassembled amphiphilic copolymers. [20][21][22][23] Pre-assembly provides good control over composition and surface functionality due to the use of preformed polymers. [24,25] Interesting examples are reported by Voit et al where thermoresponsive core-shell nanogels were prepared by self-assembly of poly(NiPAAm)-graft -poly(2-carboxyethyl-2-oxazoline) followed by crosslinking by electron-beam irradiation.…”

Section: Introductionmentioning

confidence: 99%

Controlling Size and Surface Chemistry of Cationic Nanogels by Inverse Microemulsion ATRP

Simakova

Averick

Jazani

et al. 2022

Macro Chemistry & Physics

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The unique properties of cationic nanogels, such as their hydrophilicity and high loading capacity, make them a promising platform as drug delivery agents, particularly for the delivery of hydrophilic biomolecules. Although several synthetic methods exist for cationic nanogels, polymerization in dispersed media is advantageous due to its ability to provide control over composition and high monomer conversion. However, polymer droplets typically suffer from a significant increase in size during polymerization due to the Ostwald ripening process. Herein, the preparation of cationic nanogels by atom transfer radical polymerization under inverse microemulsion conditions of a hydrophilic inimer that prevents monomer diffusion and hence limits droplets’ growth during polymerization is reported. Additionally, the surface functionality of the nanogels can be modulated by the application of hydrophobic reactive surfactants or by grafting hydrophilic shells to form core‐shell cationic nanogels. The synthesized cationic nanogels are biocompatible, internalized to HEK 293 cells, and have a high complexation ability for plasmid DNA.

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Tumor‐Selective Activation of Toll‐Like Receptor 7/8 Agonist Nano‐Immunomodulator Generates Safe Anti‐Tumor Immune Responses upon Systemic Administration

Hao

et al. 2022

Angewandte Chemie

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Agonists of innate pattern recognition receptors such as toll‐like receptors (TLRs) prime adaptive anti‐tumor immunity and hold promise for cancer immunotherapy. However, small‐molecule TLR agonists cause immune‐related adverse effects (irAEs) after systemic administration. Herein, we report a polymeric nano‐immunomodulator (cN@SS‐IMQ) that is inactive until it is selectively metabolized to an active immunostimulant within the tumor. cN@SS‐IMQ was obtained via self‐assembly of a cyclo(Arg‐Gly‐Asp‐D‐Phe‐Lys)‐modified amphiphilic copolymeric prodrug. Upon systemic administration, cN@SS‐IMQ preferentially accumulated at tumor sites and responded to high intracellular glutathione levels to release native imidazoquinolines for dendritic cell maturation, thereby enhancing the infiltration of T lymphocytes. Collectively, cN@SS‐IMQ tends to activate the immune system without irAEs, thus suggesting its promising potential for safe systemic targeting delivery.

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Bisphosphonate-loaded nanogels attentuate liver fibrosis by repolarization of M2-type macrophages

Cited by 4 publications

References 0 publications

Tumor‐Selective Activation of Toll‐Like Receptor 7/8 Agonist Nano‐Immunomodulator Generates Safe Anti‐Tumor Immune Responses upon Systemic Administration

Tumor‐Selective Activation of Toll‐Like Receptor 7/8 Agonist Nano‐Immunomodulator Generates Safe Anti‐Tumor Immune Responses upon Systemic Administration

Controlling Size and Surface Chemistry of Cationic Nanogels by Inverse Microemulsion ATRP

Tumor‐Selective Activation of Toll‐Like Receptor 7/8 Agonist Nano‐Immunomodulator Generates Safe Anti‐Tumor Immune Responses upon Systemic Administration

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