Targeted delivery of doxorubicin chemoreagent to breast cancer cells using chitosan-folic acid micelles
Targeted delivery of doxorubicin chemoreagent to breast cancer cells using chitosan-folic acid micelles
Farnoosh attari,1,*Amirhossein Alizadeh,2Reza Karimi-Soflou,3
1. Department of Animal Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran 2. Department of Animal Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran 3. Department of biomedical engineering, Amirkabir University of Technology, Tehran, Iran
Introduction: Using nanoparticles for anticancer drug delivery can increase drug circulation time and decrease the effective drug concentration, leading to reduced side effects. It is well known that tumor capillaries develop malformation in their structure, leading to increased permeability. As a result, nanoparticles can be accumulated in the tumor area. In addition, cancer cells overexpress some receptors, such as folic acid receptors on their surface, which can be used for active targeting. In the present study, we have used amphiphilic polymeric micelles decorated with folic acid to deliver chemoreagent doxorubicin to the breast cancer cells. For optimum drug delivery, nanoparticles must be able to keep their cargo in the circulation, but also capable of releasing the drug in the tumor site. pH-sensitive delivery systems can maintain the drug in the physiologic pH; however, they discharge it in the acidic tumor environment. Therefore, in our study, we have used chitosan as a pH-sensitive polymer for micelle fabrication.
Methods: Micelles were fabricated using a high-speed homogenization method. Ninhydrin and DLS assays were used to determine the characterization and size of fabricated nanoparticles. To assess the cell viability, MTT assay was used. Fluorescent microscopy used to show the uptake of nanocarriers into the treated cells. Also hemolysis test was used to show the effect of obtained nanocarriers on red blood cells. At last, the effect of drug-loaded nanoparticles was assessed in tumor-bearing mice.
Results: First, we have proved the presence of chitosan and folic acid in our fabricated micelles using ninhydrin assay. Also, the DLS results confirmed that our micelle size was around 150 nm. The drug release assay showed the sustained release of doxorubicin with the maximum release after 80 hours. In vitro experiments indicated that doxorubicin-loaded nanoparticles could effectively reduce the cell viability of breast cancer cells in 48 and 72 hours. Also, fluorescent microscopy images confirmed the uptake of doxorubicin in the nanoparticle-treated cancer cells. Additionally, hemolysis study demonstrated the biocompatibility of the nanoparticles for in vivo application. At last, in vivo experiment revealed that systemic injection of doxorubicin-loaded nanoparticles could effectively decrease tumor volume.
Conclusion: To conclude, our data showed that sustained drug release from our nanoparticles makes them a suitable and practical option for the suppression of breast cancer cells growth.