Preparation of pH/NIR dual-responsive metal-organic framework com-posite nanoparticles co-loaded with indocyanine green and siSphK1 and its in vitro anti-non-small-cell lung cancer study
10.3969/j.issn.1000-4718.2025.08.011
- VernacularTitle:共载吲哚菁绿和siSphK1的pH/NIR双响应性金属有机框架复合纳米颗粒的制备及体外抗非小细胞肺癌的研究
- Author:
Bingjie LÜ
1
;
Xiaohong YAN
;
Fei YU
;
Haoran HU
;
Lulu WANG
;
Yang YANG
Author Information
1. 滨州医学院附属医院重症医学科,山东 滨州 256603
- Publication Type:Journal Article
- Keywords:
indocyanine green;
sphingosine kinase 1;
pH/NIR dual-responsiveness;
non-small-cell lung cancer
- From:
Chinese Journal of Pathophysiology
2025;41(8):1550-1558
- CountryChina
- Language:Chinese
-
Abstract:
AIM:This study aims to design pH/near-infrared(NIR)dual-responsive metal-organic framework composite nanoparticles co-loaded with indocyanine green(ICG)and sphingosine kinase 1(SphK1)siRNA(siSphK1),and to evaluate their anticancer efficacy against non-small-cell lung cancer A549 cells.METHODS:The ZIF-8 nanopar-ticles were synthesized and loaded with ICG and siSphK1 to prepare ZIF-8@ICG@siSphK1 nanoparticles.Their morpholo-gy,particle size,surface charge,and crystalline structure were characterized through transmission electron microscopy,dynamic light scattering,and X-ray diffraction.Stability,siSphK1 encapsulation and protection,and pH/NIR response were assessed.The gene silencing efficacy and anticancer activity in A549 cells were evaluated using Western blot,RT-qPCR,MTT assay,flow cytometry,and reactive oxygen species(ROS)fluorescence staining.RESULTS:The ZIF-8@ICG@siSphK1 nanoparticles exhibited a typical polyhedral structure with an average particle size of(76.8±0.9)nm and a ζ potential of(9.2±0.1)mV.The nanoparticles effectively encapsulated siSphK1,protecting it from RNase degra-dation,and demonstrated excellent NIR responsiveness with a photothermal conversion efficiency of 39.7%.After 10 h of 808 nm laser irradiation,siRNA cumulative release was significantly higher at pH 5.5 compared with pH 7.4.In A549 cells,the nanoparticles efficiently delivered siSphK1 under NIR irradiation,significantly down-regulated SphK1 gene ex-pression,inhibited cell proliferation,induced apoptosis,and increased intracellular ROS levels.CONCLUSION:The ZIF-8@ICG@siSphK1 nanoparticles effectively induce cytotoxic effects against A549 cells through gene silencing and pho-tothermal therapy.