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Thermosensitive biotinylated hydroxypropyl cellulose-based polymer micelles as a nano-carrier for cancer-targeted drug delivery

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Abstract

In this article, we report the synthesis of a novel amphiphilic hydroxypropyl cellulose-based polymer (HPC-PEG-Chol) that contained poly (ethylene glycol) and cholesterol-containing moieties with specific degrees of substitution. The resulting polymer was subsequently converted to a biotin conjugate (HPC-PEG-Chol-biotin), to develop a new potential cancer-targeted drug delivery system. The biotin conjugate was used to prepare micelles via the dialysis method. The polymeric micelles in aqueous solution presented a lower critical solution temperature (LCST) of 39.8 oC. The critical micelle concentration (CMC) values of the polymeric micelles at 25 and 45 °C were evaluated to be about 0.32 and 0. 25 g/L, respectively. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) analyses of the micelles revealed the spherical shapes of the micelles, with 84 nm mean diameters that increased with the increase of the temperature above LCST. The hydrophobic anticancer drug paclitaxel (PTX) was loaded in the micelles and the in vitro release behaviors of PTX were investigated at different temperatures. The release profile of PTX from the polymeric micelles revealed a thermosensitivity, since its release rate was higher at 41 °C than at 37 °C. Fluorescent microscopy analyses confirm that the PTX-loaded HPC-PEG-Chol-biotin is superior in cellular uptake, with very strong adsorption to both HeLa and MDA-MB-231 cancer cell lines. MTT assay in normal cells indicated that HPC-PEG-Chol-biotin micelles have great potential to be safely used in tumor-targeting chemotherapy.

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Acknowledgments

The authors would like to thank Iran National Science Foundation for financially supporting this research. We are grateful to Azarbaijan Shahid Madani University Research Council for partial support of this study. The authors' warm thanks are also extended to Ms. Veghar Barri for her assistance with the English language.

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Authors and Affiliations

  1. Chemistry Department, Science Faculty, Azarbaijan Shahid Madani University, P.O. Box: 53714-161, 5375171379, Tabriz, Iran

    Massoumeh Bagheri & Shaghayegh Shateri

  2. Department of Tissue Engineering, Scholl of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Hassan Niknejad

  3. Nanomedicine and Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Hassan Niknejad

  4. Polymer Laboratory, Organic Chemistry department, Chemistry Faculty, Tabriz University, Tabriz, Iran

    Ali Akbar Entezami

Authors
  1. Massoumeh Bagheri
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  2. Shaghayegh Shateri
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  3. Hassan Niknejad
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  4. Ali Akbar Entezami
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Correspondence to Massoumeh Bagheri.

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Bagheri, M., Shateri, S., Niknejad, H. et al. Thermosensitive biotinylated hydroxypropyl cellulose-based polymer micelles as a nano-carrier for cancer-targeted drug delivery. J Polym Res 21, 567 (2014). https://doi.org/10.1007/s10965-014-0567-4

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