Protected amine-functional initiators for the synthesis of α-amine homo- and heterotelechelic poly(2-ethyl-2-oxazoline)s

Mazrad, Zihnil Adha Islamy; Lai, May C.; Davis, Thomas P.; Nicolazzo, Joseph A.; Thurecht, Kristofer J.; Leiske, Meike N.; Kempe, Kristian

doi:10.1039/d2py00649a

Cited by 8 publications

(15 citation statements)

References 72 publications

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“…Deprotection of phthalimide functionality on polymer ends was done as previously described. 62 Deprotection was achieved via hydrazinolysis with 50 mol excess hydrazine to the polymer at 120 °C, and subsequent purification with basic workup, precipitation into ether, and dialysis in 1 kDa membrane against MQ were achieved without consequential deprotection of dioxolane aldehyde protecting groups.…”

Section: Synthesis Of Polymersmentioning

confidence: 99%

Schiff-Base Cross-Linked Poly(2-oxazoline) Micelle Drug Conjugates Possess Antiferroptosis Activity in Numerous In Vitro Cell Models

Morrow,

Mazrad,

Warne

et al. 2024

Biomacromolecules

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A great deal of nanocarriers have been applied to induce ferroptosis in cancer research, yet there are limited examples of nanocarrier formulations to rescue ferroptosis, which can be applied to neurodegeneration, inflammation, liver damage, kidney disease, and more. Here, we present the synthesis, characterization, and in vitro evaluation of pH-responsive, core-cross-linked micelle (CCM) ferrostatin-1 (Fer-1) conjugates with amine, valproic acid, and biotin surface chemistries. Fer-1 release from stable and defined CCM Fer-1 conjugates was quantified, highlighting the sustained release for 24 h. CCM Fer-1 conjugates demonstrated excellent ferroptosis rescue by their antilipid peroxidation activity in a diverse set of cell lines in vitro. Additionally, CCMs showed tunable cell association in SH-SY5Y and translocation across an in vitro blood–brain barrier (BBB) model, highlighting potential brain disease applications. Overall, here, we present a polymeric Fer-1 delivery system to enhance Fer-1 action, which could help in improving Fer-1 action in the treatment of ferroptosis-related diseases.

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Section: Synthesis Of Polymersmentioning

confidence: 99%

Schiff-Base Cross-Linked Poly(2-oxazoline) Micelle Drug Conjugates Possess Antiferroptosis Activity in Numerous In Vitro Cell Models

Morrow,

Mazrad,

Warne

et al. 2024

Biomacromolecules

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“…[ 36 ] The cROP of (2‐oxazolines) proceeds with higher functional group tolerance, which has permitted the synthesis of PMOXa from initiators bearing alkyne groups [ 33 ] or protected thiols [ 37 ] and amines. [ 38 ]…”

Section: Polymer Synthesismentioning

confidence: 99%

“…[36] The cROP of (2-oxazolines) proceeds with higher functional group tolerance, which has permitted the synthesis of PMOXa from initiators bearing alkyne groups [33] or protected thiols [37] and amines. [38] Hydroxyl groups are not strictly "clickable", but nevertheless are used in many coupling reactions, as they are chemically stable and can readily be obtained from quenching, e.g. by the treat-ment of active chain-ends in cROP with basic water.…”

Section: Polymer Conjugationmentioning

confidence: 99%

Trends in the Synthesis of Polymer Nano‐ and Microscale Materials for Bio‐Related Applications

Coats

Cochereau

Dinu

et al. 2023

Macromolecular Bioscience

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Polymeric nano‐ and microscale materials bear significant potential in manifold applications related to biomedicine. This is owed not only to the large chemical diversity of the constituent polymers, but also to the various morphologies these materials can achieve, ranging from simple particles to intricate self‐assembled structures. Modern synthetic polymer chemistry permits the tuning of many physicochemical parameters affecting the behavior of polymeric nano‐ and microscale materials in the biological context. In this Perspective, an overview of the synthetic principles underlying the modern preparation of these materials is provided, aiming to demonstrate how advances in and ingenious implementations of polymer chemistry fuel a range of applications, both present and prospective.

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“…Recently, our group reported that N -acylated poly(aminoester) (NPAE)-based comb polymers with pendant carboxylic acid groups − allow efficient functionalization with amine-functionalized compounds, including macromolecules, which offer a possibility of different structure formation and attachment of drugs and targeting ligands. Another class of polymers with a versatile range of available derivatives and end-group and side-chain functionalization ,− that offer great potential in biomedical applications because of their water solubility, biocompatibility, antifouling, and stealth effect are poly(2-oxazoline)s (POx). , The attachment of telechelic and multifunctional POx to NPAE-based comb polymers allows for incorporation of low-fouling moieties and the adjustment of their size and aspect ratio in a single step. Previously, it was reported that NPAE-based comb polymers showed cellular uptake through passive diffusion of cell membranes followed by efficient targeting of mitochondria with no negative effect to the cells in a mouse embryo fibroblast cell line (NIH/3T3) and a rat dopaminergic neural cell line (N27).…”

Section: Introductionmentioning

confidence: 99%

Comparison of the Anti-inflammatory Activity and Cellular Interaction of Brush Polymer–N-Acetyl Cysteine Conjugates in Human and Murine Microglial Cell Lines

et al. 2023

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Microglia-mediated neuroinflammation is commonly associated with neurodegeneration and has been implicated in several neurological disorders, such as Alzheimer's disease and Parkinson's disease. Therefore, it is crucial to develop a detailed understanding of the interaction of potential nanocarriers with microglial cells to efficiently deliver anti-inflammatory molecules. In this study, we applied brush polymers as a modular platform to systematically investigate their association with murine (BV-2) and human (HMC3) microglial cell lines in the presence and absence of the pro-inflammatory inducer lipopolysaccharide (LPS) using flow cytometry. Brush polymers of different sizes and shapes, ranging from ellipsoid to worm-like cylinders, were prepared through a combination of the two building blocks carboxylated Nacylated poly(aminoester)s (NPAEs)-based polymers and poly(2-ethyl-2oxazoline)-NH 2 (PEtOx-NH 2 ) and characterized by 1 H NMR spectroscopy, size exclusion chromatography, and small-angle neutron scattering. Generally, ellipsoidal particles showed the highest cellular association. Moreover, while no significant differences in murine cell association were observed, the brush polymers revealed a significant accumulation in LPS-activated human microglia compared to resting cells, emphasizing their higher affinity to activated HMC3 cells. Brush polymers with the highest cell association were further modified with the anti-inflammatory agent N-acetyl cysteine (NAC) in a reversible manner. The brush polymer−NAC conjugates were found to significantly attenuate the production of interleukin 6 (p < 0.001) in LPS-activated HMC3 cells compared to LPS-activated BV-2 cells. Thus, the presented brush polymer− NAC conjugates showed a high anti-inflammatory activity in human microglia, suggesting their potential for disease-targeted therapy of microglial-mediated neuroinflammation in the future.

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Protected amine-functional initiators for the synthesis of α-amine homo- and heterotelechelic poly(2-ethyl-2-oxazoline)s

Abstract: Polymers bearing amine moieties are highly valuable for their ability to conjugate and/or complex a variety of molecules. However, their incorporation into synthetic macromolecules remains challenging. Poly(2-oxazolines) (POx) are a...

Cited by 8 publications

References 72 publications

Schiff-Base Cross-Linked Poly(2-oxazoline) Micelle Drug Conjugates Possess Antiferroptosis Activity in Numerous In Vitro Cell Models

Schiff-Base Cross-Linked Poly(2-oxazoline) Micelle Drug Conjugates Possess Antiferroptosis Activity in Numerous In Vitro Cell Models

Trends in the Synthesis of Polymer Nano‐ and Microscale Materials for Bio‐Related Applications

Comparison of the Anti-inflammatory Activity and Cellular Interaction of Brush Polymer–N-Acetyl Cysteine Conjugates in Human and Murine Microglial Cell Lines

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