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pH-sensitive chitosan-PEG-decorated hollow mesoporous silica nanoparticles could be an effective treatment for acute myeloid leukemia (AML)

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Abstract

Improved treatment of acute myeloid leukemia (AML) could be possible by longer retention of anticancer drugs in the bloodstream. In this study, it was aimed to obtain improved treatment against AML by providing prolonged blood levels of doxorubicin and ensuring endosomal escape by the proton sponge effect. With this aim, pH-sensitive and chitosan-poly ethylene glycol (Cs-PEG) coated doxorubicin-loaded hollow mesoporous silica nanoparticles (C-HMSN-DN) were prepared. Nanoparticles (NPs) were characterized by dynamic light scattering (DLS), zeta potential, transmission electron microscopy (TEM), X-Ray diffraction (XRD), and nitrogen adsorption–desorption isotherms. High doxorubicin encapsulation efficacy was obtained as 90%. pH-sensitive formulations were showed higher cellular uptake and found more effective against human leukemia cell line (HL60) than non-pH sensitive formulations. In vivo studies showed that Cs-PEG coating prolonged blood circulation time tremendously in comparison to unmodified nanoparticles and free doxorubicin. The designed drug delivery system (DDS) can be more effective by endosomal escape to eliminate myeloid cells which are granular cells containing a great number of lysosomes. In conclusion, we present a drug delivery system that provides a prolonged blood circulation time due to Cs-PEG coating and effective drug delivery via pH-sensitive drug release and endosomal escape for AML treatment.

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Acknowledgements

TEM, SEM, XRD, and BET analyses were performed in Middle East Technical University Central Laboratory. Special thanks to ILKO ARGEM for FTIR analysis. A part of this study was supported by Hacettepe University Coordinatorship of Scientific Research Projects with the project code THD-2016-12890. Special thanks to Prof. Fernandez-Megia and his team for giving Chitosan-PEG as a kind gift. Also, thanks to DEVA Holding A.S. for doxorubicin which was a kind gift from them.

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Authors and Affiliations

  1. Department of Nanotechnology and Nanomedicine, Grad School of Science and Engineering, Hacettepe University, Ankara, Turkey

    G. Ultav

  2. Department of Pharmaceutical Technology, Faculty of Pharmacy, Inonu University, Malatya, Turkey

    H. Tonbul

  3. Department of Basic Oncology, Hacettepe University Cancer Institute, Ankara, Turkey

    E. Tavukcuoglu & G. Esendagli

  4. Laboratory Animals Research And Application Centre (HUDHAM), Hacettepe University, Ankara, Turkey

    S. C. Ozturk

  5. Department of Pharmaceutical Technology, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey

    S. Akbas & Y. Capan

  6. Department of Pharmacy Service, Vocational School of Health Services, Bilecik Seyh Edebali University, Bilecik, Turkey

    A. Sahin

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  1. G. Ultav
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Ultav, G., Tonbul, H., Tavukcuoglu, E. et al. pH-sensitive chitosan-PEG-decorated hollow mesoporous silica nanoparticles could be an effective treatment for acute myeloid leukemia (AML). J Nanopart Res 24, 40 (2022). https://doi.org/10.1007/s11051-022-05404-8

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