Shaanxi Key Laboratory of Natural Products and Chemical Biology, College of Chemistry & Pharmacy, Northwest A&F University, Yangling 712100, China.
Shaanxi Key Laboratory of Natural Products and Chemical Biology, College of Chemistry & Pharmacy, Northwest A&F University, Yangling 712100, China.
J Colloid Interface Sci. 2022 Jun;615:386-394. doi: 10.1016/j.jcis.2022.01.189. Epub 2022 Feb 1.
Nitric oxide (NO)-mediated gas therapy (GT) and alkyl radical (R•) therapy (ART) are emerging cancer therapy modes, and multi-mode therapy has been recognized as an attractive strategy for enhancing anti-cancer efficacy. In this work, a thermal-responsive R• initiator 2,2'-azobis[2-(2-imidazolin-2-yl)propane] dihydrochloride (AIBI)-loaded glycol-targeting NO nanogenerator was constructed by first the covalent conjugation of thermal-responsive NO donor of S-nitrosothiols (RSNO) on the surface of mesoporous silica-coated gold nanorods (AuNRs@MSN), then the coating of a supramolecular complex of amino pillar[5]arene (NP5) and galactose derivative (G), and finally the loading of AIBI. The glycol-targeting NO nanogenerator demonstrated specific targeting ability to HepG2 cells owing to the recognition between galactose residues and asialoglycoprotein receptors (ASGPR). Specially, upon 808 nm near-infrared (NIR) irradiation, the AIBI-loaded NO nanogenerator generated hyperthermia to achieve photothermal therapy (PTT), and further GT and ART resulted from the thermal responsiveness of RSNO and AIBI, respectively. In vitro experiments revealed that the AIBI-loaded glyco-targeting NO nanogenerator had good biocompatibility and exhibited effective inhibition to the proliferation of HepG2 cells. This work provides a novel way to supramolecular hybrid drug delivery systems for triple-mode targeting therapy of PTT/GT/ART.
一氧化氮（NO）介导的气体治疗（GT）和烷基自由基（R•）治疗（ART）是新兴的癌症治疗模式，多模式治疗已被认为是增强抗癌疗效的一种有吸引力的策略。在这项工作中，通过共价键合将热响应型一氧化氮供体 S-亚硝基硫醇（RSNO）接枝到介孔硅包覆的金纳米棒（AuNRs@MSN）表面，然后再涂覆超分子配合物氨基酸柱[5]芳烃（NP5）和半乳糖衍生物（G），最后负载 AIBI，构建了一种热响应型 R•引发剂 2,2'-偶氮[2-(2-咪唑啉-2-基)丙烷]二盐酸盐（AIBI）负载的糖靶向 NO 纳米发生器。由于半乳糖残基与去唾液酸糖蛋白受体（ASGPR）之间的识别，糖靶向 NO 纳米发生器对 HepG2 细胞表现出特异性靶向能力。特别地，在 808nm 近红外（NIR）照射下，负载 AIBI 的 NO 纳米发生器产生的热量实现光热治疗（PTT），进一步 GT 和 ART 分别来自 RSNO 和 AIBI 的热响应性。体外实验表明，负载 AIBI 的糖靶向 NO 纳米发生器具有良好的生物相容性，并对 HepG2 细胞的增殖表现出有效的抑制作用。这项工作为 PTT/GT/ART 三重靶向治疗的超分子杂化药物传递系统提供了一种新的方法。
