doi:10.1038/nindia.2015.161 Published online 8 December 2015
Researchers have created a nanocomplex ferry that has the potential to deliver antimitotic drugs selectively to liver cancer cells.
The researchers used the drug combretastatin A4 (CA4) or 2-methoxyestradiol (2ME) encapsulated in co-polymeric nanocomplexes, with chimeric cetuximab-functionalized coronas to create the potent drug delivery system for human Hepatocellular Carcinoma (HCC) cells. The strategy accelerated the internalization of the nanocomplexes in HCC cells. This resulted in significant inhibition of cell proliferation, increased apoptosis and enhanced the depolymerization of microtubules, as compared to the non-targeted nanocomplexes and free drugs.
Since HCC cells are highly vascularized tumours, they show increased metastasis and invasive properties along with higher cell migration properties. The cetuximab-functionalized nanocomplexes potently blocked the cancer cell migration more than the free drugs CA4 or 2ME alone. This suggested a strong antimigratory potential of cetuximab nanocomplexes.
The combinatorial effects of the nanocomplexes significantly enhanced the anticancer effects of antimitotic drugs in cancer cells. This strategy facilitated the internalization of CA4 or 2 ME delivery via receptor- mediated endocytosis in HCC cells, in which the epidermal growth factor receptor (EGFR) is overexpressed. It may also be useful for selectively targeting microtubules in these cells, the researchers say.
1. Poojari, R. et al. A chimeric cetuximab-functionalized corona as a potent delivery system for microtubule-destabilizing nanocomplexes to hepatocellular carcinoma cells: A focus on EGFR and tubulin intracellular dynamics. Mol. Pharmaceutics 12, 3908-3923 (2015) doi: 10.1021/acs.molpharmaceut.5b00337