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Transferrin-Modified Vitamin-E/Lipid Based Polymeric Micelles for Improved Tumor Targeting and Anticancer Effect of Curcumin

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Abstract

Purpose

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).

Methods

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.

Results

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.

Conclusions

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.

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Abbreviations

CUR:

Curcumin

C-VPM:

Curcumin loaded VPM

DMEM:

Dulbecco’s modified Eagle’s media

DOPE:

Dioleoyl phosphatidylethanolamine

FBS:

Heat-inactivated fetal bovine serum

FC:

Free curcumin

h:

Hour

Hela:

Human cervical carcinoma cells

HepG2:

Human hepatic carcinoma cells

MEM:

Minimuim essential medium

MTT:

Dimethylthiazol-2-yl)-2,5-di-phenyltetrazolium bromide

PEG-PE:

Polyethylene glycol-phosphatidyl ethanolamine

pNP-PEG-PE:

p-Nitrophenylcarbony-PEG-PE

PPM:

PEG-PE based micelles

Tf:

Transferrin

Tf-CVPM:

Curcumin loaded Tf-VPM

Tf-PP:

Transferrin modified PEG-PE

Tf-VP:

Transferrin modified Vitamin E based polymer

Tf-VPM:

Transferrin modified vitamin E based micelles

VPM:

Vitamin E based micelles

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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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Authors and Affiliations

  1. Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Jawahar Nagar, Shameerpet, Hyderabad, Telangana, 500078, India

    Omkara Swami Muddineti, Preeti Kumari, Balaram Ghosh & Swati Biswas

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  1. Omkara Swami Muddineti
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  2. Preeti Kumari
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  3. Balaram Ghosh
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  4. Swati Biswas
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Correspondence to Swati Biswas.

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Muddineti, O.S., Kumari, P., Ghosh, B. et al. Transferrin-Modified Vitamin-E/Lipid Based Polymeric Micelles for Improved Tumor Targeting and Anticancer Effect of Curcumin. Pharm Res 35, 97 (2018). https://doi.org/10.1007/s11095-018-2382-9

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