Targeted Codelivery of Docetaxel and Atg7 siRNA for Autophagy Inhibition and Pancreatic Cancer Treatment.
Miaozun ZhangWei ZhangGuping TangHebin WangMin WuWeiming YuZhenfeng ZhouYiping MouXingang LiuPublished in: ACS applied bio materials (2019)
As the fourth leading cause of cancer-related deaths worldwide, pancreatic cancer has a higher basal level of autophagy as compared to other epithelial tumors. Recently, increasing evidence suggested that docetaxel (DTX) triggered autophagy in pancreatic cancer cells which promoted cancer cell survival after chemotherapy. Therefore, we constructed an amphiphilic block copolymer that can form micelles to simultaneously codeliver with siAtg7 and DTX for effective inhibition of tumor cells grown in vitro and in vivo . The iRGD peptide internalized on the surface of the vehicle could target to tumors and increase the penetration of vehicle into solid tumors. By downregulating the expression of Atg7 gene, the DTX-induced autophagy was inhibited, which improved the DTX therapeutic outcomes during the treatment of pancreatic cancer.
Keyphrases
- cell death
- endoplasmic reticulum stress
- signaling pathway
- oxidative stress
- cancer therapy
- locally advanced
- drug delivery
- poor prognosis
- diabetic rats
- drug release
- squamous cell carcinoma
- radiation therapy
- wastewater treatment
- gene expression
- high glucose
- drug induced
- metabolic syndrome
- rectal cancer
- insulin resistance
- smoking cessation
- glycemic control
- plant growth
- replacement therapy