Chondroitin Sulfate-Linked Prodrug Nanoparticles Target the Golgi Apparatus for Cancer Metastasis Treatment.
Haohuan LiPei ZhangJingwen LuoDanrong HuYuan HuangZhi-Rong ZhangYao FuTao GongPublished in: ACS nano (2019)
Metastasis is a multistep biological process regulated by multiple signaling pathways. The integrity of the Golgi apparatus plays an important role in these signaling pathways. Inspired by the mechanism and our previous finding about accumulation of chondroitin sulfate in Golgi apparatus in hepatic stellate cells, we developed a Golgi apparatus-targeting prodrug nanoparticle system by synthesizing retinoic acid (RA)-conjugated chondroitin sulfate (CS) (CS-RA). The prodrug nanoparticles appeared to accumulate in the Golgi apparatus in cancer cells and realized RA release under an acidic environment. We confirmed that CS-RA exhibited successful inhibition of multiple metastasis-associated proteins expression in vitro and in vivo by disruption of the Golgi apparatus structure. Following loading with paclitaxel (PTX), the CS-RA based nanoformulation (PTX-CS-RA) inhibited migration, invasion, and angiogenesis in vitro and suppressed tumor growth and metastasis in 4T1-Luc bearing mice. This multistep targeted nanoparticle system potentially enhanced the effect of antimetastasis combined with chemotherapy.
Keyphrases
- rheumatoid arthritis
- endoplasmic reticulum
- cancer therapy
- disease activity
- ankylosing spondylitis
- signaling pathway
- induced apoptosis
- interstitial lung disease
- hyaluronic acid
- systemic lupus erythematosus
- drug delivery
- poor prognosis
- epithelial mesenchymal transition
- squamous cell carcinoma
- systemic sclerosis
- skeletal muscle
- cell cycle arrest
- endoplasmic reticulum stress
- photodynamic therapy
- papillary thyroid
- metabolic syndrome
- combination therapy
- cell migration
- ionic liquid
- insulin resistance
- squamous cell
- adipose tissue
- walled carbon nanotubes