Dendritic polyglycerolsulfate-SS-poly(ester amide) micelles for the systemic delivery of docetaxel: pushing the limits of stability through the insertion of π–π interactions

Braatz, Daniel; Peter, Justus H; Dimde, Mathias; Quaas, Elisa; Ludwig, Kai; Achazi, Katharina; Schirner, Michael; Ballauff, Matthias; Haag, Rainer

doi:10.1039/d3tb00055a

Cited by 3 publications

(1 citation statement)

References 52 publications

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“…In this context, dithiothreitol (DTT) (Scheme ) appeared to be an excellent choice as the A 2 monomer. First of all, it is available commercially, second it provides two free hydroxyl functional groups for (bio)drug-conjugation by carbonate/carbamate linker, which should also pave the way for stimuli responsive drug release by backbiting by the free thiol, − when generated due to the cleavage of the disulfide linkage in the reducing intracellular environment. With this hypothesis, herein we have successfully demonstrated the synthesis of an amphiphilic HB-PDS-Camptothecin (CPT) conjugate ( P1 , Scheme ) with exceptionally high drug loading content (DLC).…”

Section: Introductionmentioning

confidence: 99%

Bioreducible Amphiphilic Hyperbranched Polymer-Drug Conjugate for Intracellular Drug Delivery

Bera,

Bej,

Kanjilal

et al. 2024

Bioconjugate Chem.

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This paper reports synthesis of a bioreducible hyperbranched (HB) polymer by A 2 +B 3 approach from commercially available dithiothreitol (DTT) (A 2 ) and an easily accessible trifunctional monomer (B 3 ) containing three reactive pyridyl-disulfide groups. Highly efficient thiol-activated disulfide exchange reaction leads to the formation of the HB polymer (M w = 21000; Đ = 2.3) with bioreducible disulfide linkages in the backbone and two different functional groups, namely, hydroxyl and pyridyl-disulfide in the core and periphery, respectively, of the HB-polymer. Postpolymerization functionalization of the hydroxylgroups with camptothecin (CPT), a topoisomerase inhibitor and known anticancer drug, followed by replacing the terminal pyridyldisulfide groups with oligo-oxyethylene-thiol resulted in easy access to an amphiphilic HB polydisulfide-CPT conjugate (P1) with a very high drug loading content of ∼40%. P1 aggregated in water (above ∼10 μg/mL) producing drug-loaded nanoparticles (D h ∼ 135 nm), which showed highly efficient glutathione (GSH)-triggered release of the active CPT. Mass spectrometry analysis of the GSH-treated P1 showed the presence of the active CPT drug as well as a cyclic monothiocarbonate product, which underpins the cascade-degradation mechanism involving GSH-triggered cleavage of the labile disulfide linkage, followed by intramolecular nucleophilic attack by the in situ generated thiol to the neighboring carbonate linkage, resulting in release of the active CPT drug. The P1 nanoparticle showed excellent cellular uptake as tested by confocal fluorescence microscopy in HeLa cells by predominantly endocytosis mechanism, resulting in highly efficient cell killing (IC 50 ∼ 0.6 μg/mL) as evident from the results of the MTT assay, as well as the apoptosis assay. Comparative studies with an analogous linear polymer-CPT conjugate showed much superior intracellular drug delivery potency of the hyperbranched polymer.

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Section: Introductionmentioning

confidence: 99%

Bioreducible Amphiphilic Hyperbranched Polymer-Drug Conjugate for Intracellular Drug Delivery

Bera,

Bej,

Kanjilal

et al. 2024

Bioconjugate Chem.

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Exploring the potential of silymarin-loaded nanovesicles as an effective drug delivery system for cancer therapy: in vivo, in vitro, and in silico experiments

Hajinezhad,

Roostaee,

Nikfarjam

et al. 2024

Naunyn-Schmiedeberg's Arch Pharmacol

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NMR of soft matter systems

Wallace

2023

Nuclear Magnetic Resonance

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This chapter summarises recent advances and applications of solid-state, solution-state and gel-state NMR techniques to study soft matter systems. Original research articles published between March 2022 and March 2023 are discussed that cover liquid crystals, surfactants, gels, polymer solutions and other soft matter systems. Each section of the review focuses on a different NMR technique, including 1D and 2D solution-state experiments, 2H NMR, nuclear Overhauser effect (NOE) measurements, pulsed-field gradient (diffusion) NMR, relaxation measurements, experiments on quadrupolar counterions and solid-state NMR.

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Dendritic polyglycerolsulfate-SS-poly(ester amide) micelles for the systemic delivery of docetaxel: pushing the limits of stability through the insertion of π–π interactions

Abstract: Highly stable micelles are facilitated by π–π interactions in an amphiphilic block copolymer system consisting of dPGS-SS-POxPPh-Py, where each building block contributes a particular ability.

Cited by 3 publications

References 52 publications

Bioreducible Amphiphilic Hyperbranched Polymer-Drug Conjugate for Intracellular Drug Delivery

Bioreducible Amphiphilic Hyperbranched Polymer-Drug Conjugate for Intracellular Drug Delivery

Exploring the potential of silymarin-loaded nanovesicles as an effective drug delivery system for cancer therapy: in vivo, in vitro, and in silico experiments

NMR of soft matter systems

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