Hyper-branched multifunctional carbon nanotubes carrier for targeted liver cancer therapy

Abstract

The systemic toxicity of anticancer drugs regularly restricts the use of conventional chemotherapy to treat cancer. In this study, the limitations overcome by profitably fabricating a multifunctional nanocarrier system to carry the anticancer drug into the specific location of the cancer cells. The polyethylene glycol (PEG) was functionalized in the carboxylated multiwalled carbon nanotubes (MWCNT-COOH) through an esterification reaction (MWCNT-PEG). The targeting ligand of folic acid (FA) was covalently bonded with hyperbranched poly-L-lysine (HBPLL) using adipic acid (AA) as a cross-linking agent. Doxorubicin (DOX), an anticancer drug, was effectively loaded on MWCNT-PEG-AA-HBPLL-FA carrier loading, and in-vitro drug release was investigated by UV–Vis spectrophotometer. The chemical functionalization, morphological properties, crystalline nature, surface charge, and thermal stability of the synthesized materials were studied by FT-IR, FE-SEM, HR-TEM, DLS, and TGA techniques. In-vitro cytotoxicity and anticancer properties of DOX-loaded nanocarrier were studied in human liver cancer (HepG2) cells and human embryonic kidney (HEK293) cells. The activities of caspases (caspase −3, −8 & −9) were analyzed using luminometry. The intrinsic apoptosis pathway proteins (Bcl-2 & BAX) were determined by western blot and RT-PCR analysis. The synthesized DOX-loaded nanocarriers exhibited increased cytotoxicity and apoptosis in liver HepG2 cells. The results suggest that the DOX-loaded nanocarrier possesses strong anticancer properties and could be an applicable and potential drug carrier for liver cancer chemotherapy.

Keywords

• Carbon nanotubes
• Doxorubicin
• HepG2 liver cancer cell line
• Multifunctional nanocarrier system