Construction of folate receptors and mitochondria targeting celastrol-loaded PAMAM nano-drug delivery system and its in vitro anti-inflammatory effect
10.16438/j.0513-4870.2022-0539
- VernacularTitle:靶向叶酸受体和线粒体的载雷公藤红素PAMAM纳米递药系统构建及体外抗炎作用
- Author:
Zi-qi JING
;
Xue WANG
;
Tian-yue YAN
;
Yu-jie ZHANG
;
Peng-kai MA
- Publication Type:Research Article
- Keywords:
rheumatoid arthritis;
celastrol;
polyamide-amine dendrimer;
folic acid;
mitochondria
- From:
Acta Pharmaceutica Sinica
2023;58(3):550-559
- CountryChina
- Language:Chinese
-
Abstract:
Pro-inflammatory macrophages play key regulatory role in the occurrence and development of rheumatoid arthritis (RA). In this study, we constructed a celastrol (Cel)-loaded polyamide-amine dendrimer (PAMAM) drug delivery system, which could target folate receptor and mitochondria. It could target inflammatory macrophages and realize chemo-photothermal synergistic therapy. Using PAMAM as the nano-carrier, folate receptor-targeting group folic acid (FA) and mitochondria-targeting group IR808 (also known as the photothermal agent) were conjugated with PAMAM through amide reaction, and then complexed with anti-inflammatory drug Cel to prepare the FA-PAMAM-IR808/Cel nanocomplex. In vitro characterization results showed that the drug loading efficiency of the nanocomplex was 50.90%, particle size was between 130 and 160 nm, average potential was between 1.0 and 3.5 mV, the drug release showed pH sensitivity, temperature reached to 42.5 ℃ after near-infrared (NIR) light irradiation for 10 min. In vitro cellular uptake experiments showed that the nanocomplex had obvious folate receptor-targeting and mitochondria-targeting ability. Following irradiation with NIR light, the cytotoxicity and cellular apoptosis enhanced. The secretion of pro-inflammatory factors tumor necrosis factor α (TNF-α), interleukin (IL)-1β, IL-6 and nitric oxide (NO) decreased in a concentration-dependent manner. This study provided insights for the development of novel anti-RA nanomedicines.
