Fabrication of polymeric sorafenib coated chitosan and fucoidan nanoparticles: Investigation of anticancer activity and apoptosis in colorectal cancer cells
Yu Zhou,
Jin Liu,
Sai Ma,
Xiaodong Yang,
Zhenzhen Zou,
Wen Lu,
Tingjun Wang,
Chunrong Sun,
Chungen Xing
Affiliations
Yu Zhou
Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, 215000, Jiangsu Province, China; Department of General Surgery, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, 215000, Jiangsu Province, China
Jin Liu
Department of Infectious Diseases, The Affiliated Infectious Diseases Hospital, Suzhou Medical College of Soochow University, The Fifth People's Hospital of Suzhou, Suzhou, 215000, Jiangsu Province, China
Sai Ma
Department of Central Laboratory, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, 215000, Jiangsu Province, China
Xiaodong Yang
Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, 215000, Jiangsu Province, China
Zhenzhen Zou
Department of Laboratory, The Fourth Affiliated Hospital of Soochow University, Dushuhu Public Hospital Affiliated to Soochow University, Suzhou, 215000, Jiangsu Province, China
Wen Lu
Department of General Surgery, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, 215000, Jiangsu Province, China
Tingjun Wang
Department of General Surgery, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, 215000, Jiangsu Province, China
Chunrong Sun
Department of General Surgery, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, 215000, Jiangsu Province, China; Corresponding author.
Chungen Xing
Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, 215000, Jiangsu Province, China; Corresponding author.
The most prevalent form of colon cancer also ranks high among cancer-related deaths globally. Traditional chemotherapy drugs do not provide sufficient therapeutic efficacy, and advanced colon cancer demonstrates considerable resistance to chemotherapy. As an oral kinase inhibitor, sorafenib (SOR) suppresses the growth of tumour cells, the formation of new blood vessels, and the death of cancer cells. Unfortunately, sorafenib's limited bioavailability, rapid metabolism, and poor solubility have severely limited its clinical use. We developed nanoparticles targeting P-selectin and SOR, with fucoidan (FU) as a ligand. The SOR-CS-FU-NPs were developed by coating polylactide-co-glycolide nanoparticles with chitosan and FU through electrostatic interaction. The SOR-CS-FU-NPs exhibited an average particle diameter of 209.98 ± 1.25 nm and a polydisperse index (PDI) of 0.229 ± 0.022. The SOR-CS-FU nanoparticles exhibited a continuous release pattern for up to 120 h. The SOR-CS-FU nanoparticles exhibited cytotoxicity 8 times greater than free SOR in HCT116 colorectal cancer cells. The cellular absorption of Rhodamine-CS-FU-NPs was three times more than that of free Rhodamine and 19 times greater than that of Rhodamine-CS-NPs. Enhanced reactive oxygen species (ROS) generation and mitochondrial membrane potential damage were also shown in SOR-CS-FU-NPs. An investigation of cell death found that SOR-CS-FU-NPs had an apoptosis index that was 7.5 times greater than free SOR. After that, the SOR-CS-FU-NPs demonstrated a more significant inhibition of cell migration, leading to a wound closure of about 5 %. No toxicity was shown in the non-cancer VERO cell line when exposed to the developed NPs. Taken together, these results provide strong evidence that biocompatible SOR-CS-FU-NPs fabricated effective carriers for the targeted delivery of dasatinib to colorectal cancer.
