Thermo-responsive nano-in-micro particles for MRI-guided chemotherapy

Ziwei Zhang; Yuexin Wang; Marwa M.I. Rizk; Ruizheng Liang; Connor J.R. Wells; Pratik Gurnani; Fenglei Zhou; Gemma Louise Davies; Gareth R. Williams

doi:10.1016/j.msec.2022.112716

Thermo-responsive nano-in-micro particles for MRI-guided chemotherapy

Ziwei Zhang, Yuexin Wang, Marwa M.I. Rizk, Ruizheng Liang, Connor J.R. Wells, Pratik Gurnani, Fenglei Zhou, Gemma Louise Davies^*, Gareth R. Williams^*

^*Corresponding author for this work

Chemistry

Research output: Contribution to journal › Article › peer-review

6 Citations (Scopus)

Abstract

In this work, we develop nano-in-micro thermo-responsive microspheres as theranostic systems for anti-cancer hyperthermia. Firstly, layered double hydroxide (LDH) nanoparticles were synthesized and subsequently loaded with the chemotherapeutic agents methotrexate (MTX) or 5-fluorouracil (5FU). The drug-loaded LDH particles were then co-encapsulated with superparamagnetic iron oxide nanoparticles (SPIONs) into poly(acrylamide-co-acrylonitrile) microparticles via spray drying. The SPIONs are able to act as MRI contrast agents, thus resulting in potential theranostic formulations. Concave microparticles were observed by electron microscopy, and elemental mapping results suggest the LDH and SPION particles were homogeneously distributed inside the microparticles. In vitro dissolution tests showed that the drug was released over a prolonged period of time with the microspheres having distinct release curves at 37 and 43 °C. The relaxivity (r₂) profiles were also found to be different over the temperature range 35 to 46 °C. Mathematical relationships between r₂, release and temperature data were established, demonstrating that the microparticles have the potential for use in MRI-guided therapy. In vitro cell experiments revealed that the formulations permit synergistic hyperthermia-aided chemotherapy in cultured Caco-2 and A549 cells. Thus, the microparticles prepared in this work have potential as smart stimuli-responsive theranostics for hyperthermia-aided chemotherapy.

Original language	English
Article number	112716
Number of pages	14
Journal	Biomaterials advances
Volume	134
Early online date	14 Feb 2022
DOIs	https://doi.org/10.1016/j.msec.2022.112716
Publication status	Published - Mar 2022

Bibliographical note

Funding Information:
The authors gratefully thank Dr. Andrew Weston and Dr. Tom Gregory for assistance with electron microscopy and energy dispersive X-ray spectroscopy experiments. MMIR thanks the Missions sector in the Egyptian Ministry of Higher Education and the British Council Egypt for funding as a part of the Newton-Mosharafa scheme, as well as the Department of Chemistry at UCL for financial support. CJRW thanks the EPSRC and SFI Centre for Doctoral Training in Advanced Characterisation of Materials (EP/L015277/1) for funding. FLZ was supported by a NIHR UCLH Biomedical Research Centre (BRC) grant, UK-MRC ImagingBioPro grant (MR/R025673/1), the UCL Department of Medical Physics and Biomedical Engineering and EPSRC (EP/M020533/1 ; CMIC Pump-Priming Award).

Publisher Copyright:
© 2022 Elsevier B.V.

ASJC Scopus subject areas

Biomedical Engineering
Biomaterials
Bioengineering

UN SDGs

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

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Cite this

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title = "Thermo-responsive nano-in-micro particles for MRI-guided chemotherapy",

abstract = "In this work, we develop nano-in-micro thermo-responsive microspheres as theranostic systems for anti-cancer hyperthermia. Firstly, layered double hydroxide (LDH) nanoparticles were synthesized and subsequently loaded with the chemotherapeutic agents methotrexate (MTX) or 5-fluorouracil (5FU). The drug-loaded LDH particles were then co-encapsulated with superparamagnetic iron oxide nanoparticles (SPIONs) into poly(acrylamide-co-acrylonitrile) microparticles via spray drying. The SPIONs are able to act as MRI contrast agents, thus resulting in potential theranostic formulations. Concave microparticles were observed by electron microscopy, and elemental mapping results suggest the LDH and SPION particles were homogeneously distributed inside the microparticles. In vitro dissolution tests showed that the drug was released over a prolonged period of time with the microspheres having distinct release curves at 37 and 43 °C. The relaxivity (r2) profiles were also found to be different over the temperature range 35 to 46 °C. Mathematical relationships between r2, release and temperature data were established, demonstrating that the microparticles have the potential for use in MRI-guided therapy. In vitro cell experiments revealed that the formulations permit synergistic hyperthermia-aided chemotherapy in cultured Caco-2 and A549 cells. Thus, the microparticles prepared in this work have potential as smart stimuli-responsive theranostics for hyperthermia-aided chemotherapy.",

author = "Ziwei Zhang and Yuexin Wang and Rizk, {Marwa M.I.} and Ruizheng Liang and Wells, {Connor J.R.} and Pratik Gurnani and Fenglei Zhou and Davies, {Gemma Louise} and Williams, {Gareth R.}",

note = "Funding Information: The authors gratefully thank Dr. Andrew Weston and Dr. Tom Gregory for assistance with electron microscopy and energy dispersive X-ray spectroscopy experiments. MMIR thanks the Missions sector in the Egyptian Ministry of Higher Education and the British Council Egypt for funding as a part of the Newton-Mosharafa scheme, as well as the Department of Chemistry at UCL for financial support. CJRW thanks the EPSRC and SFI Centre for Doctoral Training in Advanced Characterisation of Materials (EP/L015277/1) for funding. FLZ was supported by a NIHR UCLH Biomedical Research Centre (BRC) grant, UK-MRC ImagingBioPro grant (MR/R025673/1), the UCL Department of Medical Physics and Biomedical Engineering and EPSRC (EP/M020533/1 ; CMIC Pump-Priming Award). Publisher Copyright: {\textcopyright} 2022 Elsevier B.V.",

year = "2022",

month = mar,

doi = "10.1016/j.msec.2022.112716",

language = "English",

volume = "134",

journal = "Biomaterials advances",

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T1 - Thermo-responsive nano-in-micro particles for MRI-guided chemotherapy

AU - Zhang, Ziwei

AU - Wang, Yuexin

AU - Rizk, Marwa M.I.

AU - Liang, Ruizheng

AU - Wells, Connor J.R.

AU - Gurnani, Pratik

AU - Zhou, Fenglei

AU - Davies, Gemma Louise

AU - Williams, Gareth R.

N1 - Funding Information: The authors gratefully thank Dr. Andrew Weston and Dr. Tom Gregory for assistance with electron microscopy and energy dispersive X-ray spectroscopy experiments. MMIR thanks the Missions sector in the Egyptian Ministry of Higher Education and the British Council Egypt for funding as a part of the Newton-Mosharafa scheme, as well as the Department of Chemistry at UCL for financial support. CJRW thanks the EPSRC and SFI Centre for Doctoral Training in Advanced Characterisation of Materials (EP/L015277/1) for funding. FLZ was supported by a NIHR UCLH Biomedical Research Centre (BRC) grant, UK-MRC ImagingBioPro grant (MR/R025673/1), the UCL Department of Medical Physics and Biomedical Engineering and EPSRC (EP/M020533/1 ; CMIC Pump-Priming Award). Publisher Copyright: © 2022 Elsevier B.V.

PY - 2022/3

Y1 - 2022/3

N2 - In this work, we develop nano-in-micro thermo-responsive microspheres as theranostic systems for anti-cancer hyperthermia. Firstly, layered double hydroxide (LDH) nanoparticles were synthesized and subsequently loaded with the chemotherapeutic agents methotrexate (MTX) or 5-fluorouracil (5FU). The drug-loaded LDH particles were then co-encapsulated with superparamagnetic iron oxide nanoparticles (SPIONs) into poly(acrylamide-co-acrylonitrile) microparticles via spray drying. The SPIONs are able to act as MRI contrast agents, thus resulting in potential theranostic formulations. Concave microparticles were observed by electron microscopy, and elemental mapping results suggest the LDH and SPION particles were homogeneously distributed inside the microparticles. In vitro dissolution tests showed that the drug was released over a prolonged period of time with the microspheres having distinct release curves at 37 and 43 °C. The relaxivity (r2) profiles were also found to be different over the temperature range 35 to 46 °C. Mathematical relationships between r2, release and temperature data were established, demonstrating that the microparticles have the potential for use in MRI-guided therapy. In vitro cell experiments revealed that the formulations permit synergistic hyperthermia-aided chemotherapy in cultured Caco-2 and A549 cells. Thus, the microparticles prepared in this work have potential as smart stimuli-responsive theranostics for hyperthermia-aided chemotherapy.

AB - In this work, we develop nano-in-micro thermo-responsive microspheres as theranostic systems for anti-cancer hyperthermia. Firstly, layered double hydroxide (LDH) nanoparticles were synthesized and subsequently loaded with the chemotherapeutic agents methotrexate (MTX) or 5-fluorouracil (5FU). The drug-loaded LDH particles were then co-encapsulated with superparamagnetic iron oxide nanoparticles (SPIONs) into poly(acrylamide-co-acrylonitrile) microparticles via spray drying. The SPIONs are able to act as MRI contrast agents, thus resulting in potential theranostic formulations. Concave microparticles were observed by electron microscopy, and elemental mapping results suggest the LDH and SPION particles were homogeneously distributed inside the microparticles. In vitro dissolution tests showed that the drug was released over a prolonged period of time with the microspheres having distinct release curves at 37 and 43 °C. The relaxivity (r2) profiles were also found to be different over the temperature range 35 to 46 °C. Mathematical relationships between r2, release and temperature data were established, demonstrating that the microparticles have the potential for use in MRI-guided therapy. In vitro cell experiments revealed that the formulations permit synergistic hyperthermia-aided chemotherapy in cultured Caco-2 and A549 cells. Thus, the microparticles prepared in this work have potential as smart stimuli-responsive theranostics for hyperthermia-aided chemotherapy.

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DO - 10.1016/j.msec.2022.112716

M3 - Article

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JO - Biomaterials advances

JF - Biomaterials advances

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ER -

Thermo-responsive nano-in-micro particles for MRI-guided chemotherapy

Abstract

Bibliographical note

ASJC Scopus subject areas

UN SDGs

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