Water-Soluble Napthalimide-Conjugated N-Nitrosamine-Based Block Copolymers for Photoinduced Nitric Oxide Delivery and Cell Imaging,ACS Applied Polymer Materials

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Water-Soluble Napthalimide-Conjugated N-Nitrosamine-Based Block Copolymers for Photoinduced Nitric Oxide Delivery and Cell Imaging
ACS Applied Polymer Materials ( IF 4.4 ) Pub Date : 2024-01-02 , DOI: 10.1021/acsapm.3c02759
Soumya Paul _{1,

2} , Shilpendu Ghosh ₂ , Manish Kumar _{1,

2} , Tanmoy Maity _{1,

2} , Arindam Mukherjee ₂ , Priyadarsi De _{1,

2}

Affiliation

N-Nitrosamine-derived nitric oxide (NO) delivery agents find widespread use in diverse biomedical applications, including cancer therapy. To understand how NO is released from these compounds and acts within cells, herein, we report a facile approach to synthesize N-nitrosamine-bound water-soluble napthalimide-based block copolymers (BCPx-NO) with improved regulation over their molecular weight and aqueous solution self-assembly. These polymers exhibit a fluorescence “turn-on” response upon photostimulated (365 nm, 3.71 mW/cm²) NO release, delivering 47–53 μM of NO within 10 h, while their concentration varied from 0.26 to 0.60 mg/mL. This accounts for approximately 67–75% of the theoretically bound NO within the polymers. The fluorescence “turn-on” response is characteristic of the small-molecule NO donor (NOD), although the emission time has a longer half-life in the polymers. The type of NO released from the NOD is a nitric oxide radical (^•NO), as per the electron paramagnetic resonance spectroscopy results. The in vitro NO release in response to the photoirradiation and the consequent acquired fluorescence are corroborated using flow cytometry and confocal imaging studies. It was also manifested that these NO conjugated polymers can physically encapsulate doxorubicin (DOX) in aqueous environment, and the synergistic effect of DOX and NO is reflected in the exhibited cytotoxicity against the MCF-7 (human breast adenocarcinoma) cells. The spatiotemporally modulated NO release steered fluorescence “turn-on” may find abundant biomedical applications.

中文翻译：

用于光诱导一氧化氮传递和细胞成像的水溶性萘酰亚胺共轭 N-亚硝胺嵌段共聚物

N-亚硝胺衍生的一氧化氮 (NO) 递送剂广泛用于多种生物医学应用，包括癌症治疗。为了了解 NO 如何从这些化合物中释放并在细胞内发挥作用，本文报告了一种合成N -亚硝胺结合的水溶性萘二酰亚胺基嵌段共聚物 ( BCPx-NO ) 的简便方法，并改进了对其分子量和水性的调节溶液自组装。^{这些聚合物在光刺激（365 nm，3.71 mW/cm 2} ）NO 释放时表现出荧光“开启”响应，在 10 小时内释放 47–53 μM 的 NO，而其浓度在 0.26 至 0.60 mg/mL 之间变化。这约占聚合物中理论上结合的 NO 的 67-75%。尽管发射时间在聚合物中的半衰期较长，但荧光“开启”响应是小分子 NO 供体 ( NOD ) 的特征。根据电子顺磁共振波谱结果，NOD释放的 NO 类型是一氧化氮自由基 ( ^{• NO)。}使用流式细胞术和共聚焦成像研究证实了响应光照射的体外NO释放和随后获得的荧光。还表明，这些NO缀合聚合物可以在水性环境中物理封装阿霉素（DOX），并且DOX和NO的协同作用体现在对MCF-7（人乳腺癌）细胞表现出的细胞毒性上。时空调节的一氧化氮释放引导荧光“开启”可能会找到丰富的生物医学应用。

更新日期：2024-01-02

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