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Implementation of electrochemical impedance spectroscopy to evaluate HER-2 aptamer conjugation to Ecoflex® nanoparticles for docetaxel delivery in breast cancer cells

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Abstract

Aptamers are affinity molecules with high specificity, proposed as excellent alternatives to antibodies in targeting and detecting applications due to their smaller size, higher stability, and simplicity of production and modification compared with antibodies. Due to lack of a sensitive and simple method to quantitatively evaluate attachment of aptamer to nanoparticles (NPs), optimization of the attachment process was not considered in most of previously studied aptamer-targeted drug delivery systems. The aim of current study was to demonstrate the utility of electrochemical impedance spectroscopy (EIS) technique in this field. Ecoflex® polymeric NPs loaded with docetaxel (DTX-NPs) were fabricated via electrospraying technique, and HER-2-specific aptamer molecules were attached via amide bonds (Apt-DTX-NPs). Using EIS method, the time period of various stages of aptamer conjugation was optimized, by comparing the amount of aptamer molecules attached to the DTX-NPs. The results of in vitro studies on optimum Apt-DTX-NPs demonstrated that the proposed delivery system could significantly enhance the cellular uptake and the cytotoxic effect against HER-2 positive cell line in comparison with non-targeted or Herceptin-targeted DTX-NPs. Thus, aptamer conjugation could improve the in vitro performance of Ecoflex NPs, which could be suggested as a potential DTX delivery system in HER-2 overexpressing cancers. In this regard, EIS method could play its role as a sensitive quantification method to obtain the optimized aptamer-conjugated NP systems.

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Abbreviations

EIS:

Electrochemical impedance spectroscopy

Apt:

Aptamer

DTX:

Docetaxel

ER:

Estrogen

PR:

Progesterone

EGFR:

Epidermal growth factor receptor

AC:

Alternating current

MTT:

3-[4, 5-Dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide

EDC:

N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride

DMF:

N,N-dimethyl formamide

NHS:

N-hydroxysuccinimide

RPMI:

Roswell Park Memorial Institute

FBS:

Fetal bovine serum

NPs:

Nanoparticles

DTX-NPs:

Non-targeted docetaxel nanoparticles

Blank NPs:

Docetaxel-free nanoparticles

Apt-NPs:

Docetaxel-free aptamer-targeted nanoparticles

Hcp-NPs:

Docetaxel-free Herceptin-targeted nanoparticles

Apt-DTX-NPs:

Aptamer-targeted docetaxel nanoparticles

Hcp-DTX-NPs:

Herceptin-targeted docetaxel nanoparticles

RhB:

Rhodamine B

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Acknowledgements

The authors appreciate financial support of Isfahan University of Medical Sciences.

Author information

Authors and Affiliations

  1. Department of Pharmaceutics, School of Pharmacy and Novel Drug Delivery Systems Research Centre, Isfahan University of Medical Sciences, Isfahan, Iran

    Jaleh Varshosaz & Erfaneh Ghassami

  2. Department of Nanotechnology Engineering, Faculty of Advanced Sciences and Technology, University of Isfahan, Isfahan, Iran

    Abdollah Noorbakhsh

  3. Department of Pharmaceutical Biotechnology, School of Pharmacy, Isfahan University of Medical Sciences, Isfahan, Iran

    Ali Jahanian-Najafabadi

  4. Department of Pharmacology, School of Pharmacy, Isfahan University of Medical Sciences, Isfahan, Iran

    Mohsen Minayian

  5. Department of Pharmaceutics, Faculty of Pharmacy and Novel Drug Delivery Systems Research Centre, Isfahan University of Medical Sciences, PO Box 81745-359, Isfahan, Iran

    Jaleh Varshosaz

Authors
  1. Jaleh Varshosaz
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  2. Erfaneh Ghassami
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  3. Abdollah Noorbakhsh
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  4. Ali Jahanian-Najafabadi
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Correspondence to Jaleh Varshosaz.

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Varshosaz, J., Ghassami, E., Noorbakhsh, A. et al. Implementation of electrochemical impedance spectroscopy to evaluate HER-2 aptamer conjugation to Ecoflex® nanoparticles for docetaxel delivery in breast cancer cells. J Appl Electrochem 49, 87–97 (2019). https://doi.org/10.1007/s10800-018-1273-4

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  • DOI: https://doi.org/10.1007/s10800-018-1273-4

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