Abstract

Nanomaterials are the foundations of Nanotechnology, which are measured in nanoscales, Carbon nanotubes are one of the interesting nanomaterials, studied for over 25 years because of their superlative properties such as high surface area, electrical and thermal conductivity, high biocompatibility, flexibility, resistance to corrosion and nanosize. According to research, carbon nanotubes are applied in sensing, water treatment, and drug delivery, mainly used to deliver the anticancer drugs. In our work, functionalization of multi walled carbon nanotubes done by covalent and non-covalent functionation methods, covalent functionalization showed better dispersing efficiency in aqueous medium and compatible with biological systems with damaging the crystal lattice of carbon nanotubes. Non covalent functionalization helps to derivatized with active compounds, surface adsorption or attachment of various molecules or antibodies, which subsequently helps in targeting the site and to produce therapeutic effects. Different formulations prepared by functionalized MWCNTs and multiple functionalization of MWCNTs done by binding the drug and antibodies to prepare functionalized MWCNTs 5-Fluorouracil complexes. The Cytotoxicity assay was carried out for the obtained new targeting formulations to analyze the effect of all the formulations on HCT116 cell line. The percentage death was determined based on the viability of the cells in the appropriate vehicle controls. In this study, we report the successful functionalization, binding of 5 Fluorouracil, antibodies to MWCNTs, and cells viability of all prepared formulations for the development of novel carbon based anticancer drug delivery system. Functionalized MWCNTs-5-Fluorouracil antibodies composite at concentration above 2.5 µg/mL exhibited ≥ 50% cytotoxicity post normalization with compound control to negate precipitation observed with the compound. All the formulations showed the precipitations indicating antitumor activity and biocompatibility.

Highlights

  • Colorectal cancer (CRC) is a cancer that occurs in large intestine or rectum

  • Functionationalization of MWCNTs followed by binding of 5- Fluorouracil 17-19 a) Covalent functionalization done by initial acidic treatment followed by treatment with hydrochloric acid: Initial acidic treatment given to MWCNTs by using HNO3 and H2SO4, which leads to produce oxidized MWCNTs

  • Preparation of Functionalized MWCNTs formulation for cell viability assay In the present study, all formulations were processed as mentioned in table 1 and 2, prepared compounds were used to treat the HCT cells each time

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Summary

INTRODUCTION

Colorectal cancer (CRC) is a cancer that occurs in large intestine or rectum. CRC possess four stages, at higher stages cancer spread to other organs such as liver and lungs. Eventhough nanoparticles, dendrimers and liposomes have been tried to load and target anticancer drugs, carbon nanotubes (CNT) have been increasingly utilized in the field of cancer therapy. MWCNTs must possess characteristic properties such as solubility, stability, retainment in blood circulation To achieve these properties, CNTs are functionalized. Once suitable functionalized MWCNTs are obtained these are loaded with anticancer drug and monoclonal antibodies. Bevacizumab is a recombinant humanized monoclonal antibody which is approved for use in metastatic colorectal cancer It is approved with 5-Fluorouracil based therapy for second line metastatic colorectal cancer. Pristine MWCNTs are functionalized by covalent and non covalent methods. These functionalized MWCNTs are loaded with Bevacizumab and 5Fluorouracil individually and in combination. HCT 116 is a human colon cancer cell line used in therapeutic research and drug screening

MATERIALS AND METHODS
Antibody
Findings
CONCLUSION
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