Designed inorganic porous nanovector with controlled release and MRI features for safe administration of doxorubicin

Simo Näkki; Julie T-W Wang; Jianwei Wu; Li Fan; Jimi Rantanen; Tuomo Nissinen; Mikko I Kettunen; Matilda Backholm; Robin H A Ras; Khuloud T Al-Jamal; Vesa-Pekka Lehto; Wujun Xu

doi:10.1016/j.ijpharm.2018.10.074

Designed inorganic porous nanovector with controlled release and MRI features for safe administration of doxorubicin

Simo Näkki, Julie T-W Wang, Jianwei Wu, Li Fan, Jimi Rantanen, Tuomo Nissinen, Mikko I Kettunen, Matilda Backholm, Robin H A Ras, Khuloud T Al-Jamal, Vesa-Pekka Lehto, Wujun Xu

Department of Applied Physics, Faculty of Science and Forestry, University of Eastern Finland, Kuopio 70211, Finland; School of Cancer and Pharmaceutical Sciences, Faculty of Life Sciences & Medicine, King's College London, London SE1 9NH, UK.
School of Cancer and Pharmaceutical Sciences, Faculty of Life Sciences & Medicine, King's College London, London SE1 9NH, UK.
Department of Pharmaceutical Analysis, School of Pharmacy, and The State Key Laboratory of Cancer Biology (CBSKL), The Fourth Military Medical University, Xi'an, Shaanxi 710032, China; Department of Oncology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
Department of Pharmaceutical Analysis, School of Pharmacy, and The State Key Laboratory of Cancer Biology (CBSKL), The Fourth Military Medical University, Xi'an, Shaanxi 710032, China. Electronic address: [email protected].
Department of Applied Physics, Faculty of Science and Forestry, University of Eastern Finland, Kuopio 70211, Finland.
A. I. Virtanen Institute for Molecular Science, 70221 Kuopio, Finland.
Aalto University
School of Cancer and Pharmaceutical Sciences, Faculty of Life Sciences & Medicine, King's College London, London SE1 9NH, UK. Electronic address: [email protected].
Department of Applied Physics, Faculty of Science and Forestry, University of Eastern Finland, Kuopio 70211, Finland. Electronic address: [email protected].

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Abstract

The inability of traditional chemotherapeutics to reach cancer tissue reduces the treatment efficacy and leads to adverse effects. A multifunctional nanovector was developed consisting of porous silicon, superparamagnetic iron oxide, calcium carbonate, doxorubicin and polyethylene glycol. The particles integrate magnetic properties with the capacity to retain drug molecules inside the pore matrix at neutral pH to facilitate drug delivery to tumor tissues. The MRI applicability and pH controlled drug release were examined in vitro together with in-depth material characterization. The in vivo biodistribution and compound safety were verified using A549 lung cancer bearing mice before proceeding to therapeutic experiments using CT26 cancer implanted mice. Loading doxorubicin into the porous nanoparticle negated the adverse side effects encountered after intravenous administration highlighting the particles' excellent biocompatibility. Furthermore, the multifunctional nanovector induced 77% tumor reduction after intratumoral injection. The anti-tumor effect was comparable with that of free doxorubicin but with significantly alleviated unwanted effects. These results demonstrate that the developed porous silicon-based nanoparticles represent promising multifunctional drug delivery vectors for cancer monitoring and therapy.

Original language	English
Pages (from-to)	327-336
Number of pages	10
Journal	INTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume	554
Early online date	2 Nov 2018
DOIs	https://doi.org/10.1016/j.ijpharm.2018.10.074
Publication status	Published - 10 Jan 2019

Keywords

A549 Cells
Animals
Antibiotics, Antineoplastic/administration & dosage
Chemistry, Pharmaceutical/methods
Colonic Neoplasms/drug therapy
Delayed-Action Preparations
Doxorubicin/administration & dosage
Drug Delivery Systems
Drug Liberation
Excipients/chemistry
Humans
Lung Neoplasms/drug therapy
Magnetic Resonance Imaging
Male
Mice
Mice, Inbred NOD
Mice, SCID
Nanoparticles
Porosity
Silicon/chemistry
Tissue Distribution

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.ijpharm.2018.10.074

Designed inorganic porous nanovector_NAKKI_Firstonline2November2018_GREEN AAM (CC BY-NC-ND)Accepted author manuscript, 3.18 MBLicence: CC BY-NC-ND
Näkki et al._Manuscript_IJP 2018Accepted author manuscript, 1.03 MBLicence: CC BY-NC-ND

Cite this

Näkki, S., Wang, J. T.-W., Wu, J., Fan, L., Rantanen, J., Nissinen, T., Kettunen, M. I., Backholm, M., Ras, R. H. A., Al-Jamal, K. T., Lehto, V.-P., & Xu, W. (2019). Designed inorganic porous nanovector with controlled release and MRI features for safe administration of doxorubicin. INTERNATIONAL JOURNAL OF PHARMACEUTICS, 554, 327-336. https://doi.org/10.1016/j.ijpharm.2018.10.074

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abstract = "The inability of traditional chemotherapeutics to reach cancer tissue reduces the treatment efficacy and leads to adverse effects. A multifunctional nanovector was developed consisting of porous silicon, superparamagnetic iron oxide, calcium carbonate, doxorubicin and polyethylene glycol. The particles integrate magnetic properties with the capacity to retain drug molecules inside the pore matrix at neutral pH to facilitate drug delivery to tumor tissues. The MRI applicability and pH controlled drug release were examined in vitro together with in-depth material characterization. The in vivo biodistribution and compound safety were verified using A549 lung cancer bearing mice before proceeding to therapeutic experiments using CT26 cancer implanted mice. Loading doxorubicin into the porous nanoparticle negated the adverse side effects encountered after intravenous administration highlighting the particles' excellent biocompatibility. Furthermore, the multifunctional nanovector induced 77% tumor reduction after intratumoral injection. The anti-tumor effect was comparable with that of free doxorubicin but with significantly alleviated unwanted effects. These results demonstrate that the developed porous silicon-based nanoparticles represent promising multifunctional drug delivery vectors for cancer monitoring and therapy.",

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AU - Nissinen, Tuomo

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AU - Ras, Robin H A

AU - Al-Jamal, Khuloud T

AU - Lehto, Vesa-Pekka

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ER -

Designed inorganic porous nanovector with controlled release and MRI features for safe administration of doxorubicin

Abstract

Keywords

UN SDGs

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