Nitroreductase (NTR)-Triggered Degradable Polymeric Sulfur Dioxide (SO₂) Prodrug.

IF 5.4 2区化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomacromolecules Pub Date : 2025-10-03 DOI:10.1021/acs.biomac.5c01047

Sagar Bag, Desoshree Ghosh, Arunava Seth, Priyadarsi De

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引用次数: 0

Abstract

A nitroreductase (NTR)-responsive sulfur dioxide (SO₂)-releasing polyurethane-based polyprodrug system is developed to execute enzyme-responsive gas therapy under hypoxic conditions. The self-assembled characteristics of the amphiphilic polyurethanes are thoroughly investigated, and their enzyme-triggered degradation is elucidated by size exclusion chromatography (SEC), hydrodynamic diameter (D_h) measurement, and microscopic study. Additionally, NTR and SO₂-responsive small molecular and polymeric fluorescent probes are synthesized, and the respective responsiveness is studied by ¹H NMR and fluorescence spectroscopy. Hypoxia-activated anticancer drug tirapazamine (TPZ) is encapsulated into the polymeric nanoaggregates, and 63% drug release is observed at pH 6.0 in the presence of NTR. Anticancer activity of the polyprodrug (SO₂ as a cytotoxic agent) and TPZ-loaded polymeric nanoaggregate (SO₂ and TPZ as cytotoxic agents) is demonstrated with cobalt chloride (CoCl₂, hypoxia mimetic mediator). Overall, the present work reveals the impact of the NTR-responsive degradable polyprodrug as an anticancer therapeutic and gives a new perspective on enzyme-responsive gas therapy.

查看原文本刊更多论文

硝基还原酶（NTR）触发的可降解聚合物二氧化硫（SO2）前药。

开发了一种基于硝基还原酶（NTR）响应的二氧化硫（SO2）释放聚氨酯的聚前药系统，用于在缺氧条件下进行酶响应气体治疗。研究了两亲性聚氨酯的自组装特性，并通过粒径隔离色谱（SEC）、流体动力学直径（Dh）测量和微观研究阐明了两亲性聚氨酯的酶促降解。此外，合成了NTR和so2响应小分子荧光探针和聚合物荧光探针，并通过1H NMR和荧光光谱研究了各自的响应性。缺氧激活的抗癌药物替拉帕胺（TPZ）被包裹在聚合物纳米聚集体中，在pH为6.0且NTR存在的情况下，观察到63%的药物释放。用氯化钴（CoCl2，模拟缺氧介质）证明了多前体药物（SO2作为细胞毒剂）和负载TPZ的聚合纳米聚集体（SO2和TPZ作为细胞毒剂）的抗癌活性。总的来说，本研究揭示了ntr反应性可降解多前体药物作为抗癌药物的影响，并为酶反应性气体治疗提供了新的视角。

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来源期刊

Biomacromolecules 化学-高分子科学

CiteScore

10.60

自引率

4.80%

发文量

417

审稿时长

1.6 months

期刊介绍： Biomacromolecules is a leading forum for the dissemination of cutting-edge research at the interface of polymer science and biology. Submissions to Biomacromolecules should contain strong elements of innovation in terms of macromolecular design, synthesis and characterization, or in the application of polymer materials to biology and medicine. Topics covered by Biomacromolecules include, but are not exclusively limited to: sustainable polymers, polymers based on natural and renewable resources, degradable polymers, polymer conjugates, polymeric drugs, polymers in biocatalysis, biomacromolecular assembly, biomimetic polymers, polymer-biomineral hybrids, biomimetic-polymer processing, polymer recycling, bioactive polymer surfaces, original polymer design for biomedical applications such as immunotherapy, drug delivery, gene delivery, antimicrobial applications, diagnostic imaging and biosensing, polymers in tissue engineering and regenerative medicine, polymeric scaffolds and hydrogels for cell culture and delivery.