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.
ABSTRACT
Polyamide-amine (PAMAM) dendrimer, a new hyperbranched macromolecular polymer, is considered an "artificial protein" by many scholars on account of its excellent chemical and biological characteristics. PAMAM has internal cavities and a large number of reactive terminal groups. These structures allow the polymer to be used as a bionic macromoleculethat could simulate the biomimetic mineralization of the natural organic matrix on the surface of tooth tissue. Specifically, PAMAM can beused as an organic template to regulate mineral nucleation and crystal growth; thus, the polymerisa more ideal dental restoration material than traditional allogenic materials. This article reviews research progress on thePAMAM-induced biomimetic mineralization of hard tooth tissues.