Poly(l-proline)-Stabilized Polypeptide Nanostructures via Ring-Opening Polymerization-Induced Self-Assembly (ROPISA)

ACS Macro Letters, Год журнала: 2024, Номер 13(8), С. 1031 - 1036

Опубликована: Июль 29, 2024

Poly(proline) II helical motifs located at the protein–water interface stabilize three-dimensional structures of natural proteins. Reported here is first example synthetic biomimetic poly(proline)-stabilized polypeptide nanostructures obtained by a straightforward ring-opening polymerization-induced self-assembly (ROPISA) process through consecutive N-carboxyanhydride (NCA) polymerization. It was found that use multifunctional 8-arm initiators critical for formation nanoparticles. Worm-like micelles as well spherical morphologies were confirmed dynamic light scattering (DLS), transmission electron microscopy (TEM), and small angle X-ray (SAXS). The loading with dyes demonstrated. This fast open-vessel procedure gives access to amino acids-based nanomaterials potential applications in nanomedicine.

Язык: Английский

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Multiple Levels of Organization in Amphiphilic Diblock Copolymers Based on Poly(γ-benzyl-l-glutamate) Produced by Aqueous ROPISA

Biomacromolecules, Год журнала: 2025, Номер unknown

Опубликована: Фев. 7, 2025

A recent method for producing amphiphilic block copolymers and nano-objects based on the ring-opening polymerization-induced self-assembly (ROPISA) in aqueous buffer is explored with respect to tunability toward nanostructures. ROPISA gives rise polypeptide unprecedented levels of organization. By employing poly(ethylene glycol) (PEG) synthetic poly(γ-benzyl-l-glutamate) (PBLG) a combination static (13C NMR, X-ray scattering, polarizing optical microscopy), thermodynamic (differential scanning calorimetry), dynamic (dielectric spectroscopy) probes, we demonstrate record six organization only found before natural materials. These could not be obtained earlier morphology investigations PEG PBLG prepared by different methods. Furthermore, type NCA monomer (BLG-NCA vs Leu-NCA) solvent treatment had an influence degree segregation, α-helical content, order-to-disorder transition temperature PEG-b-PBLG PEG-b-PLeu copolymers.

Язык: Английский

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Nanourchin‐like Uricase‐Poly(_L‐proline) Conjugate with Retained Enzymatic Activity, Mitigated Immunogenicity, and Sustained Efficacy Upon Repeated Administrations

Angewandte Chemie International Edition, Год журнала: 2025, Номер unknown

Опубликована: Март 5, 2025

The poor half-life and strong immunogenicity of proteins such as uricase (UOx), a therapeutic enzyme for chronic refractory gout hyperuricemia, are pressing clinical challenges. Although conjugation poly(ethylene glycol) (PEGylation) UOx can improve the pharmacokinetics, preexisting or induced anti-PEG antibodies, which lead to accelerate blood clearance (ABC) reduced response rate, have been major hurdle. Herein, we report facile "grafting-from" preparation nanourchin-like uricase-poly(L-proline) conjugate, namely UOx-PLP, with high grafting-density, enhanced thermal, lyophilization, freeze-thaw, proteolytic stability. Through transient preblocking strategy in synthesis, UOx-PLP overcomes activity loss retains ~82 % activity. In Sprague-Dawley rats, stimulates minimum complement activation anti-UOx antibodies. Unlike PEG-UOx gave significantly after repetitive administrations, shows no sign ABC effect. Moreover, remain almost unchanged when cross-administrated rats previously received titers Finally, efficacy five straight administrations knock-out hyperuricemia mice model, whereas experiences sharp upon same treatment. Overall, simple outstanding nonclinical results highlight enormous potential future translation.

Язык: Английский

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Nanourchin‐like Uricase‐Poly(_L‐proline) Conjugate with Retained Enzymatic Activity, Mitigated Immunogenicity, and Sustained Efficacy Upon Repeated Administrations

Angewandte Chemie, Год журнала: 2025, Номер unknown

Опубликована: Март 5, 2025

Abstract The poor half‐life and strong immunogenicity of proteins such as uricase (UOx), a therapeutic enzyme for chronic refractory gout hyperuricemia, are pressing clinical challenges. Although conjugation poly(ethylene glycol) (PEGylation) UOx can improve the pharmacokinetics, preexisting or induced anti‐PEG antibodies, which lead to accelerate blood clearance (ABC) reduced response rate, have been major hurdle. Herein, we report facile “grafting‐from” preparation nanourchin‐like uricase‐poly( L ‐proline) conjugate, namely UOx‐PLP, with high grafting‐density, enhanced thermal, lyophilization, freeze‐thaw, proteolytic stability. Through transient preblocking strategy in synthesis, UOx‐PLP overcomes activity loss retains ~82 % activity. In Sprague‐Dawley rats, stimulates minimum complement activation anti‐UOx antibodies. Unlike PEG‐UOx gave significantly after repetitive administrations, shows no sign ABC effect. Moreover, remain almost unchanged when cross‐administrated rats previously received titers Finally, efficacy five straight administrations knock‐out hyperuricemia mice model, whereas experiences sharp upon same treatment. Overall, simple outstanding nonclinical results highlight enormous potential future translation.

Язык: Английский

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ROPISA Strategy for In‐Situ Loading in Polypeptide Nanoparticles

Chemistry - An Asian Journal, Год журнала: 2025, Номер unknown

Опубликована: Апрель 28, 2025

Abstract We report a ring‐opening polymerization induced self‐assembly (ROPISA) synthetic strategy for in‐situ encapsulation of fluorescent dye molecules in poly(ʟ‐serine) based polypeptide nano‐assemblies and demonstrate their cellular bioimaging application. A bulky ʟ‐serine N‐carboxyanhydride monomer is tailor‐made polymerized using PEG‐amine as hydrophilic macroinitiator water at pH 8.5 to obtain block copolymer stable dispersions the form opalescent solutions. Both soluble dyes like Rhodamine B, HPTS insoluble Nile red are readily encapsulated ROPISA process which afforded nanoformulation direct application biological system. The nanoparticle dispersion found be stable, they have spherical morphology 25 nm size. nascent nanoparticles were nontoxic mammalian cells up 100 µg/mL non‐hemolytic Red Blood Cells. These endocytosed across cell membrane internalized cytosol, proof‐of‐concept was established by confocal microscopy. This newly developed loading opens new platform nano‐formulations both material biomedical fields.

Язык: Английский

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Degradable Diblock Copolymer Vesicles via Radical Ring-Opening Polymerization-Induced Self-Assembly in Aqueous Media

Journal of the American Chemical Society, Год журнала: 2025, Номер unknown

Опубликована: Май 30, 2025

The development of degradable polymeric vesicles is essential for next-generation controlled delivery systems and responsive materials, particularly therapy diagnostics. However, achieving precise control over their synthesis degradation behavior remains a significant challenge. Herein we report the diblock copolymer via radical ring-opening polymerization-induced self-assembly (rROPISA) in aqueous media. This approach employs copolymerization (rROP) thionolactone with water-miscible vinyl monomer to introduce cleavable thioester groups within membrane-forming polymer chains. More specifically, water-soluble poly(N,N-dimethylacrylamide) (PDMAC) precursor chain-extended by statistically copolymerizing dibenzo[c,e]oxepane-5-thione (DOT) 2-methoxyethyl acrylate (MEA) using reversible addition-fragmentation chain transfer (RAFT) dispersion polymerization formulation. disparity reactivity between DOT MEA addressed comonomer-starved feed strategy, acting as cosolvent water-insoluble DOT. feeding ensures more uniform distribution repeat units hydrophobic core block, significantly improves composition control, enables incorporation up ∼4 mol %, enhances overall comonomer conversion. Compared conventional one-shot batch syntheses, this strategy yielded superior profiles. Morphological characterization cryogenic transmission electron microscopy (cryo-TEM), dynamic light scattering (DLS) small-angle X-ray (SAXS) confirmed formation well-defined vesicles. Hydrolytic studies conducted mildly basic media led vesicle disintegration, indicated cryo-TEM, DLS, SAXS analyses. Importantly, size exclusion chromatography (SEC) analysis revealed shorter chains final molecular weight distributions comparable that nondegradable PDMAC precursor, indicating efficient hydrolytic P(MEA-stat-DOT) block. study provides valuable insights regarding rational design vinyl-based vesicles, which augurs well potential biomedical applications.

Язык: Английский

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Synthesis of poly(L-lactide)-b-poly(amino acid)s block copolymers by noncovalent protection of hetero-initiator

Polymer Chemistry, Год журнала: 2024, Номер unknown

Опубликована: Янв. 1, 2024

The noncovalent protection of Et 3 B avoids the complex and deprotection steps directly synthesizes PLA- b -PAA block copolymers.

Язык: Английский

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