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Fe3O4@ZnO core-shell nanocomposites for efficient and repetitive removal of low density lipoprotein in plasma and on blood vessel

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Abstract and Figures

Low density lipoprotein (LDL)-apheresis therapy, which directly removes LDL from plasma by LDL-adsorbents in vitro is found to be clinically effective and safe to lower the LDL content in blood to prevent cardiovascular disease. Thus, developing excellent LDL adsorbents are becoming more and more attractive. Herein, functional Fe3O4@ZnO core-shell nanocomposites have been synthesized by a facile and eco-friendly two-step method. Not only do they possess high LDL adsorption (in PBS/plasma as well as on blood vessels) and favorable magnetic targeting ability but they can also be reused conveniently, which offer the Fe3O4@ZnO core-shell nanocomposites significant potential in the removal of LDL in vitro and in vivo.
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Fe
3
O
4
@ZnO core-shell nanocomposites for
efcient and repetitive removal of low
density lipoprotein in plasma and on blood
vessel
Xiao Huang
1,2
, Juan Lu
1
, Danyang Yue
1
, Yijuan Fan
1
, Caixia Yi
1
,
Xiaoying Wang
1
, Mengxue Zhang
1
and Jun Pan
1
1
Key Laboratory for Biorheological Science and Technology of Ministry of Education, College of
Bioengineering, Chongqing University, Chongqing 400044, Peoples Republic of China
2
College of Materials and Chemical Engineering, Tongren University, Tongren 554300, Peoples Republic
of China
E-mail: panj@cqu.edu.cn
Received 22 December 2014, revised 29 January 2015
Accepted for publication 9 February 2015
Published 6 March 2015
Abstract
Low density lipoprotein (LDL)-apheresis therapy, which directly removes LDL from plasma by
LDL-adsorbents in vitro is found to be clinically effective and safe to lower the LDL content in
blood to prevent cardiovascular disease. Thus, developing excellent LDL adsorbents are
becoming more and more attractive. Herein, functional Fe
3
O
4
@ZnO coreshell nanocomposites
have been synthesized by a facile and eco-friendly two-step method. Not only do they possess
high LDL adsorption (in PBS/plasma as well as on blood vessels) and favorable magnetic
targeting ability but they can also be reused conveniently, which offer the Fe
3
O
4
@ZnO core
shell nanocomposites signicant potential in the removal of LDL in vitro and in vivo.
Keywords: low density lipoprotein, Fe
3
O
4
@ZnO core-shell nanocomposites, reusable remover,
magnetic targeting
(Some gures may appear in colour only in the online journal)
1. Introduction
Cardiovascular disease (CVD) is the leading cause of pre-
mature death worldwide, resulting in more than 16 million
mortalities each year [1]. Currently, it is of great belief that a
primary risk factor in the pathogenesis of CVD is the elevated
level of LDL in plasma [2,3]. Compellent evidence from both
experimental and clinical research also demonstrates that
lowering the LDL content in blood prevents CVD well [4,5].
For that reason, several LDL-lowering or -removing methods
have been developed and clinically used. Nevertheless, some
limitations still exist. Alimentary control, an adjunctive
therapeutic measure, is limited in its effectiveness [6]. Clini-
cally used LDL-lowering medicines, such as statins, bile acid
resins and niacin, display side effects after long-term medi-
cation (muscle pain, weakness [7], acute coronary syndromes
[8], etc). In particular, when the patients LDL level is over
3mgmL
1
in blood, alimentary control and drugs would take
no effect [9]. Rejoicingly, LDL-apheresis therapy, which
directly removes LDL from plasma by LDL-adsorbents
in vitro, is found to be clinically effective and safe, particu-
larly for familial hypercholesterolemia patients and for those
who cannot be sufciently treated by diet and drugs [10].
However, its effect, which depends on the adsorptive per-
formance of LDL-adsorbents, is still expected to be improved.
The LDL-adsorbents currently used consist of heparinized- or
sulfonated-cellulose [11], dextran [12], polyvinyl alcohol
[13], carbon composites [14] and anti-LDL antibody-carrying
poly(hydroxyethyl methacrylate) cryogel [15]; their effec-
tiveness is limited by the poor graft ratio of the small LDL-
adsorbing molecules [16,17]. What is worse, none of them
can be conveniently reusable to cut the therapy cost for the
Nanotechnology
Nanotechnology 26 (2015) 125101 (8pp) doi:10.1088/0957-4484/26/12/125101
0957-4484/15/125101+08$33.00 © 2015 IOP Publishing Ltd Printed in the UK1
... Building on this, Huang et al. (2015) developed nanocomposites of Fe 3 O 4 @ZnO core-shell to load docetaxel and encapsulate the epidermal growth factor (EGF) on the polymer. Upon stimulation with UV irradiation, the chemical structure of ZnO was rearranged to release docetaxel and EGF, resulting in obstruction of the growth of cancer cells (Huang et al., 2015). In further research, they designed a photo-responsive multifunctional drug delivery by combining Fe 3 O 4 @ZnO core-shell and amphipathic polymer of P(BA-co-HBA)-loaded docetaxel which was able to boost chemotherapy effects by UV stimulation to trigger the ZnO hydrophilic / hydrophobic transition to release the drug and to prompt the amphipathic polymer to adsorb and encapsulate EGF (Huang et al., 2016). ...
... Previously, Huang et al. (2015) studied a smart drug release system for skin protection by using ZnO nanoparticles as a UV filter loaded with benzophenone-3. The system was tested on keratinocytes and skin fibroblasts to investigate drug release upon UV irradiation. ...
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... Zinc oxide is a suitable candidate for coating the magnetic iron oxide nanoparticles due to its good properties such as non-toxic, oxidation resistance, stability, environmentally friendly, wide band gap (E g = 3.37 eV) and optical characteristics [3,4]. It was reported that the combination of magnetic iron oxides and ZnO in nanosized structures promotes advantages of both materials and shows applicability in many fields including bioengineering [5], bioseparation [6], electromagnetic wave absorption [7], photocurrent enhancement [8], solar hydrogen production [9] and especially photocatalyst [10][11][12][13][14][15][16][17][18][19]. The reported studies indicated that nanocomposites of Fe 3 O 4 (or γ-Fe 2 O 3 ) with ZnO exhibited good photocatalytic activity, magnetic separability and reusability. ...
... Thus, related to recoverability of the nanocomposites, investigation of their magnetic characteristics is very necessary. It was observed in the nanocomposites that the presence of ZnO reduces magnetization significantly and affects superparamagnetic behaviors [5,8,10,12,[14][15][16][20][21][22][23][24]. However, explanation of these observations is not clear yet. ...
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This paper presents a comprehensive view of effect of ZnO coating on structure and magnetic properties of the magnetic iron oxide/ZnO core/shell nanocomposites. The nanocomposites with Fe:Zn molar ratio of 7:1, 5:1 and 3:1 were synthesized by using two-step co-precipitation method. Crystal structure, microstructure, composition, valence state, morphology and magnetic properties of the samples were systematically investigated by using synchrotron X-ray diffraction, X-ray absorption near-edge spectroscopy, Fourier transform infrared spectra, field emission scanning electron microscope, transmission electron microscopy and vibrating sample magnetometer. The obtained results indicated that the nanocomposites exhibit superparamagnetic behavior at room temperature. Structure and magnetic properties of the nanocomposites are strongly influenced by ZnO content as microstrain increases, magnetization and blocking temperature decrease upon ZnO coating. The change in magnetic properties of the nanocomposites has been discussed based on detailed information on composition and structure, spin canting and surface effect.
... Cardioprotective effect [119] Iron oxide-zinc oxide core-shell nanocomposites Removal of LDL in plasma and blood vessel [120] Quantum dots Fluorescent probes for CV disease diagnosis [121] Manganese-doped zinc selenide quantum dots Deliver HDAC1 siRNA in cardiomyocytes [122] DNA nanostructures Cardioprotection [123,124] absorbed on the receptors on fibrin or triggered platelets play a role in advancing microbubble migration to the clots [7]. The efficacy of the "ultrasound targeted microbubble destruction" or UTMD procedure was documented for the transfer of genes and genetic drugs to the cardiac tissues and associated organs ( [7]; and references therein). ...
... It was demonstrated that the nanoformulation of "N,α-L-rhamnopyranosyl vincosamide" extracted from the leaves of Moringa oleifera using magnetic hydrogel nanocomposites possess a cardioprotective effect against doxorubicin-triggered toxicity in rat cardiac tissues [119]. Likewise, advantages of iron oxide-zinc oxide core-shell nanocomposites were highlighted in the competent and the recurring elimination of LDL in blood vessels and plasma, which will effectively reduce CV complications [120]. Quantum dots are lesser sized nanoparticles (<5 nm) and are widely used as a CV drug carrier or to fabricate biosensors. ...
Chapter
This chapter archives the state of the art concerning crucial drug delivery strategies aiding in cardiovascular therapies, including their benefits and associated challenges. The aspects which govern vascular transport and cardiovascular drug targeting have been reviewed, both from configuration and flow perspectives. In addition, the role of extracellular vesicles and exosomes, as well as the suitability of ultrasound and microbubble-mediated delivery, has been discussed. Current advancements made in the nanomedicine domain, with relevant applications pertaining to diverse categories, have been collated and discussed. A special focus has been laid on the applications of aptamers in cardiovascular drug targeting, particularly with respect to conjugation with specific coagulation factors and proteins. It also captures the potential and promises of the next generation of targeted strategies, with an eye on the foreseeable future.
... This method is detailed in our previously published article. 19 Various masses of previously synthesized Fe 3 O 4 @ZnO NCs (W: W=100:1, 50:1, 10:1, 1:1, 1:10, 1:50, 1:100, Fe 3 O 4 @ZnO: Bru) fully dispersed in an aqueous solution, then added into the acetone containing a corresponding amount of Bru, respectively. Then, the solution was ultrasonically shocked for 1h. ...
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... We can also identify the spherical and hexagonal nanoflakes forming the clusters by combining each other having low dispersion which tends to the magnetic property of the synthesized nanocomposite. 17,18 During electron irradiation there is difference in electron scattering; hence, Fe 3 O 4 appears darker because of higher electron density when compared to ZnO nanoparticles in Fig. 5c. 19 HRTEM shown in Fig. 5e gives a d spacing value of 0.19 nm (Fe 3 O 4 ) and 0.24 nm (ZnO) in the nanocomposite 20 which supports the XRD studies. ...
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