Research Article

Ultrasound-mediated in vivo biodistribution of coumarin-labeled sorafenib-loaded liposome-based nanotheranostic system

NILOP Nanomedicine Research Laboratories, National Institute of Lasers & Optronics College (NILOP-C), Pakistan Institute of Engineering & Applied Sciences, Nilore, Islamabad, 45650, Pakistan

Department of Biotechnology, Medical Genetics Research Laboratory, Quaid-i-Azam University, Islamabad, 45320, Pakistan

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Muhammad Naeem

https://orcid.org/0000-0002-3894-3085

Department of Biotechnology, Medical Genetics Research Laboratory, Quaid-i-Azam University, Islamabad, 45320, Pakistan

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Farwa Nurjis

NILOP Nanomedicine Research Laboratories, National Institute of Lasers & Optronics College (NILOP-C), Pakistan Institute of Engineering & Applied Sciences, Nilore, Islamabad, 45650, Pakistan

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Shafqat Karim

Nano Materials Research Group, Pakistan Institute of Nuclear Science & Technology (PINSTECH), Nilore, Islamabad, 45650, Pakistan

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Abida Raza

*Author for correspondence: Tel.: +92 345 771 3910;

E-mail Address: abida_rao@yahoo.com

https://orcid.org/0000-0002-4414-1070

National Center of Industrial Biotechnology, Pir Mehr Ali Shah Arid Agriculture University, Rawalpindi, 46000, Pakistan

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Published Online:25 Jan 2023https://doi.org/10.2217/nnm-2022-0137

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Abstract

Aim: This study aimed to synthesize folate-conjugated sorafenib-loaded (FCSL) liposomes for theranostic application using ultrasound (US). Materials & methods: US parameter optimization, in vitro release, anticancer effect, in vivo biodistribution, optical imaging and biocompatibility of liposomes were studied. Results: With 84% in vitro release after 4 min of US exposure at 3 MHz (1.2 mechanical index), FCSL liposomes showed lower IC₅₀ (8.70 μM) versus sorafenib (9.34 μM) against HepG2 cells. In vivo biodistribution of FCSL liposomes versus sorafenib after 9 mg/kg injection in the liver (8.63 vs 0.55) > intestine (8.45 vs 1.07) > stomach (5.62 vs 0.57) > kidney (5.46 vs 0.91) showed longer circulation time in plasma and can be tracked in mice. Conclusion: A threefold higher drug concentration in the liver in US-exposed mice makes this a successful nanotheranostic approach.

Plain language summary

Sorafenib is the first-line treatment for liver cancer, but it has low absorption due to its poor water solubility and unavoidable side effects. Liposomes can encapsulate a wide range of diagnostic and therapeutic agents. Ultrasound (US) application can lead to enhanced penetration and release at the site of action. In this study, folate-ornamented sorafenib-loaded liposomes were evaluated for safe intravenous administration, anticancer effect, biodistribution and bioavailability in mice after US application. The results of this study will help researchers understand how US and optical imaging show that coumarin-labeled liposomes can act as theranostic agents with dual properties of therapeutics and imaging. US and folate-conjugated sorafenib-loaded theranostic liposomes can be utilized as a promising approach to cancer treatment.

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Papers of special note have been highlighted as: •• of considerable interest

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Vol. 17, No. 25

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History

Received 30 May 2022

Accepted 7 December 2022

Published online 25 January 2023

Published in print October 2022

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Keywords

Author contributions

U Sarwar contributed in project execution, including experimentation, data acquisition, analysis, interpretation and manuscript write-up. M Naeem contributed to manuscript write-up. F Nurjis contributed in cell culture experimentation and data analysis. S Karim contributed to characterization of formulation. A Raza supervised and contributed to the idea, design and drafting of the work and critical revision for publication.

Financial & competing interests disclosures

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

All animal studies were approved by the ethical committee of National Institute of Lasers and Optronics, Pakistan (#NNRL-FBS-5008) according to EU directives 2010/63 for animal studies.

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