Transferrin-Modified Vitamin-E/Lipid Based Polymeric Micelles for Improved Tumor Targeting and Anticancer Effect of Curcumin
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Transferrin receptor (TfR) is up-regulated in various malignant tumors not only to meet the iron requirement, but also to increase the cell survival via participation in various cellular signaling pathways. Here we explored transferrin as ligand for Poly(ethylene Glycol) (PEG)-ylated vitamin-E/lipid (PE) core micelles (VPM).
Transferrin modified polymer was synthesized and drug loaded micelles were evaluated in 2D Hela and HepG2 cancer cells for cellular uptake and cytotoxicity and in 3D Hela spheroids for growth inhibition, uptake and penetration studies.
Targeted (Tf-VPM) and non-targeted (VPM) micelles showed mean hydrodynamic diameter of 114.2 ± 0.64 nm and 117.4 ± 0.72 nm and zeta potential was −22.8 ± 0.62 and −14.8 ± 1.74 mV, respectively. Cellular uptake study indicated that the Tf-CVPM were taken up by cancer cells (Hela and HepG2) with higher efficiency. Enhanced cytotoxicity was demonstrated for Tf-VPM compared to CVPM. Marked spheroid growth inhibition following treatment with Tf-CVPM was observed compared to the treatment with non-targeted CVPM.
The developed transferrin-modified micelles have improved ability to solubilize the loaded drugs and could actively target solid tumors by its interaction with over-expressed transferrin receptors. Therefore, the nano-micelles could be further explored for its potential utilization in cancer therapy.
Key wordsactive targeting curcumin micelles transferrin vitamin E
Curcumin loaded VPM
Dulbecco’s modified Eagle’s media
Heat-inactivated fetal bovine serum
Human cervical carcinoma cells
Human hepatic carcinoma cells
Minimuim essential medium
Polyethylene glycol-phosphatidyl ethanolamine
PEG-PE based micelles
Curcumin loaded Tf-VPM
Transferrin modified PEG-PE
Transferrin modified Vitamin E based polymer
Transferrin modified vitamin E based micelles
Vitamin E based micelles
ACKNOWLEDGMENTS AND DISCLOSURES
The work was supported in part by the grants provided by the Department of Science and Technology (CS-269/2013), Government of India and the Department of Biotechnology (BT/Bio-CARe/07/10003/2013–14), Govt of India to Swati Biswas. Omkara Swami gratefully acknowledges Indian Council of Medical Research (2014–24,190), Department of Health Research, Ministry of Health & Family Welfare, Government of India for awarding him with the Senior Research Fellowship (SRF). There are no conflicts of interest
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