Biodistribution of biodegradable polymeric nano-carriers loaded with busulphan and designed for multimodal imaging

Journal of Nanobiotechnology

Research

Khalid M. Abu-Salah¹  Fei Ye²  Ibrahim El-Serafi²  Manuchehr Abedi-Valugerdi²  Ramy El-Sayed²  Åsa Barrefelt²  Moustapha Hassan³  Ying Zhao³  Mamoun Muhammed⁴  Heba Asem⁵  Jörg Hamm⁶ 

[1] Department of Nanomedicine, King Abdullah International Medical Research Center, King Abdulaziz Medical City, PO Box 22490, 11426, Riyadh, Saudi Arabia;Division of Experimental Cancer Medicine (ECM), Department of Laboratory Medicine (LABMED), Karolinska Institutet (KI), 141 86, Stockholm, Sweden;Division of Experimental Cancer Medicine (ECM), Department of Laboratory Medicine (LABMED), Karolinska Institutet (KI), 141 86, Stockholm, Sweden;Clinical Research Center (KFC), Karolinska University Hospital Huddinge, 141 86, Stockholm, Sweden;Division of Functional Materials (FNM), Department of Materials and Nanophysics, Royal Institute of Technology (KTH), 164 40, Stockholm, Sweden;Division of Functional Materials (FNM), Department of Materials and Nanophysics, Royal Institute of Technology (KTH), 164 40, Stockholm, Sweden;Division of Experimental Cancer Medicine (ECM), Department of Laboratory Medicine (LABMED), Karolinska Institutet (KI), 141 86, Stockholm, Sweden;PerkinElmer, 68 Elm St., 01748, Hopkinton, MA, USA;

关键词: Biodegradable polymer;    Drug delivery;    Magnetic resonance imaging;    In vivo fluorescence imaging;    Biodistribution;    Busulphan;    Cancer;   

DOI  :  10.1186/s12951-016-0239-0

 received in 2016-10-06, accepted in 2016-12-03,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundMultifunctional nanocarriers for controlled drug delivery, imaging of disease development and follow-up of treatment efficacy are promising novel tools for disease diagnosis and treatment. In the current investigation, we present a multifunctional theranostic nanocarrier system for anticancer drug delivery and molecular imaging. Superparamagnetic iron oxide nanoparticles (SPIONs) as an MRI contrast agent and busulphan as a model for lipophilic antineoplastic drugs were encapsulated into poly (ethylene glycol)-co-poly (caprolactone) (PEG-PCL) micelles via the emulsion-evaporation method, and PEG-PCL was labelled with VivoTag 680XL fluorochrome for in vivo fluorescence imaging.ResultsBusulphan entrapment efficiency was 83% while the drug release showed a sustained pattern over 10 h. SPION loaded-PEG-PCL micelles showed contrast enhancement in T2*-weighted MRI with high r2* relaxivity. In vitro cellular uptake of PEG-PCL micelles labeled with fluorescein in J774A cells was found to be time-dependent. The maximum uptake was observed after 24 h of incubation. The biodistribution of PEG-PCL micelles functionalized with VivoTag 680XL was investigated in Balb/c mice over 48 h using in vivo fluorescence imaging. The results of real-time live imaging were then confirmed by ex vivo organ imaging and histological examination. Generally, PEG-PCL micelles were highly distributed into the lungs during the first 4 h post intravenous administration, then redistributed and accumulated in liver and spleen until 48 h post administration. No pathological impairment was found in the major organs studied.ConclusionsThus, with loaded contrast agent and conjugated fluorochrome, PEG-PCL micelles as biodegradable and biocompatible nanocarriers are efficient multimodal imaging agents, offering high drug loading capacity, and sustained drug release. These might offer high treatment efficacy and real-time tracking of the drug delivery system in vivo, which is crucial for designing of an efficient drug delivery system.

【 授权许可】

CC BY   
© The Author(s) 2016