Abstract
BackgroundColon cancer is a most common malignant cancer in digestive system, and it is prone to develop resistance to the commonly used chemotherapy drugs, leading to local recurrence and metastasis. Paris saponin VII (PSVII) could not only inhibit the proliferation of colon cancer cells but also effectively induce apoptosis of drug-resistant colon cancer cells and reduce the metastasis of drug-resistant colon cancer cells as well. However, PSVII was insoluble in water and fat. It displayed no selective distribution in body and could cause severe hemolysis. Herein, colon cancer targeting calcium phosphate nanoparticles were developed to carry PSVII to treat drug-resistant colon cancer.ResultsPSVII carboxymethyl-β-cyclodextrin inclusion compound was successfully encapsulated in colon cancer targeting calcium phosphate nanoparticles (PSVII@MCP-CaP) by using modified citrus pectin as stabilizer agent and colon cancer cell targeting moiety. PSVII@MCP-CaP significantly reduced the hemolysis of PSVII. Moreover, by specific accumulating in orthotopic drug-resistant colon cancer tissue, PSVII@MCP-CaP markedly inhibited the growth of orthotopic drug-resistant colon cancer in nude mice. PSVII@MCP-CaP promoted the apoptosis of drug-resistant colon cancer cells through mitochondria-mediated apoptosis pathway. Moreover, PSVII@MCP-CaP significantly inhibited the invasion and migration of drug-resistant colon cancer cells by increasing E-cadherin protein expression and reducing N-cadherin and MMP-9 protein expression.ConclusionPSVII@MCP-CaP has great potential in the treatment of drug-resistant colon cancer. This study also explores a new method to prepare active targeting calcium phosphate nanoparticles loaded with a fat and water insoluble compound in water.Graphical
Highlights
Colon cancer is a most common malignant cancer in digestive system, and it is prone to develop resistance to the commonly used chemotherapy drugs, leading to local recurrence and metastasis
The main peak of Derivative thermogravimetry (DTG) widened with tails and the overall percentage of weight loss increased, indicating that Calcium phosphate nanoparticles (CaP) nanoparticles had been modified by modified citrus pectin (MCP)
The above results indicated that Paris saponin VII (PSVII)@MCP-CaP contained calcium phosphate, PSVII and MCP
Summary
Colon cancer is a most common malignant cancer in digestive system, and it is prone to develop resistance to the commonly used chemotherapy drugs, leading to local recurrence and metastasis. PSVII was insoluble in water and fat It displayed no selective distribution in body and could cause severe hemolysis. Colon cancer targeting calcium phosphate nanoparticles were developed to carry PSVII to treat drug-resistant colon cancer. Chemotherapy is used to reduce local recurrence and metastasis of colon cancer, and improve the survival rate. Colon cancer cell is prone to develop resistance to commonly used chemotherapy drugs, leading to local recurrence and metastasis, which is the main cause of death in colon cancer patients at present [4]. It is an urgent need to find new chemotherapy drugs to treat drug-resistant colon cancer
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