Synthesis of Glutathione-Responsive Cyclomatrix Polyphosphazene for Multimodal Theranostic Nanodrug Delivery
Synthesis of Glutathione-Responsive Cyclomatrix Polyphosphazene for Multimodal Theranostic Nanodrug Delivery
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DOI：
10.1021/acsapm.3c00559
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发表时间：
2023-06
影响因子：
5
通讯作者：
Jinjin Li;Ruyue Liu;Bingyan Zhang;Feifei Bai;Ling Zhao;Zhenhao Xi
中科院分区：
文献类型：
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作者：
Jinjin Li;Ruyue Liu;Bingyan Zhang;Feifei Bai;Ling Zhao;Zhenhao Xi
在这项工作中，基于自框架聚磷腈前药和七次甲基花青染料 IR-780 的协同作用，开发了多模式（化疗/光动力/光热）治疗诊断纳米药物递送平台。首先，通过染料木黄酮（GEN）、双（4-羟苯基）二硫化物和六氯环三磷腈的多组分缩合反应制备了电负性谷胱甘肽（GSH）响应性聚磷腈前药（缩写为HGEH）。含有药物（GEN）的HGEH纳米颗粒的粒径是可调的。随后，将阳离子近红外光敏剂IR-780吸附到富电子HGEH上，得到多模式治疗诊断纳米药物递送平台HGEH-IR780。该平台被证明能够保持高稳定性，避免药物渗漏，并能够根据存在较高 GSH 浓度的肿瘤微环境实现受控药物释放。体外实验表明，HGEH-IR780在暴露于单带宽近红外激光（808 nm）时经历光热和光动力过程，同时产生热量和活性氧，从而有效杀死小鼠乳腺癌细胞（4T1）。具体而言，HGEH-IR780 在浓度为 100 μg/mL 时可抑制 4T1 细胞高达 80%。所开发的HGEH-IR780在GSH响应性抗癌活性和光动力/光热治疗方面表现出良好的结果，为多酚黄酮类多模式治疗纳米平台的构建提供了参考。
In this work, a multimodal (chemotherapeutic/photodynamic/photothermal) theranostic nanodrug delivery platform was developed based on the synergetic action of self-framed polyphosphazene prodrug and heptamethine cyanine dye IR-780. First, an electronegative glutathione (GSH)-responsive polyphosphazene prodrug abbreviated as HGEH was prepared via multicomponent condensation reaction of genistein (GEN), bis-(4-hydroxyphenyl)-disulfide, and hexachlorocyclotriphosphazene. The particle size of drug (GEN)-containing HGEH nanoparticles is adjustable. Subsequently, cationic near-infrared photosensitizer IR-780 was adsorbed onto the electron-rich HGEH to obtain the multimodal theranostic nanodrug delivery platform HGEH-IR780. The platform was demonstrated to retain high stability in avoiding drug leakage and enable controlled drug release in response to the tumor microenvironment, in which a higher GSH concentration exists. The in vitro experiments show that HGEH-IR780 undergoes photothermal and photodynamic processes to concurrently generate heat and reactive oxygen species for efficiently killing mouse breast cancer cells (4T1) upon exposure to a single-bandwidth near-infrared laser (808 nm). Specifically, HGEH-IR780 inhibits 4T1 cells by up to 80% at a concentration of 100 μg/mL. The as-developed HGEH-IR780 exhibits promising results in GSH-responsive anticancer activity and photodynamic/photothermal therapy, which provides a reference for the construction of the polyphenol flavonoid multimodal therapeutic nanoplatform.