Surface‐Functionalized Ultrasmall Superparamagnetic Nanoparticles as Magnetic Delivery Vectors for Camptothecin

Cengelli, Feride; Grzyb, Justyna A.; Montoro, Auxia; Hofmann, Heinrich; Hanessian, Stephen; Juillerat‐Jeanneret, Lucienne

doi:10.1002/cmdc.200800424

Cited by 39 publications

(27 citation statements)

References 31 publications

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“…The therapeutic agent can also be attached directly onto the IONP surface. Gendeli and coworkers [78] covalently attached an anti-cancer drug (amptothecin) to USPIOs (core diameter, 9-10 nm; hydrodynamic diameter, 52 nm) coated with polyvinylalcohol/polyvinylamine using a biodegradable linkage. Th e magnetic properties of the nanoparticles were exploited to enhance cell uptake.…”

Section: Drug and Gene Deliverymentioning

confidence: 99%

The design and utility of polymer-stabilized iron-oxide nanoparticles for nanomedicine applications

et al. 2010

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Iron-oxide nanoparticles (IONPs) represent a significant class of inorganic nanomaterial that is contributing to the current revolution in nanomedicine [1][2]. Their unique physical properties, including high surface area to volume ratios and superparamagnetism, confer useful attributes for medical applications such as magnetic resonance imaging (MRI), drug and gene delivery, tissue engineering and bioseparation [3].Two distinct classes of superparamagnetic IONP-based materials are currently used for medical applications: superparamagnetic iron-oxide (SPIO) nanoparticles with a mean particle diameter of 50-100 nm, and ultra-small superparamagnetic iron-oxide (USPIO) nanoparticles with a size below 50 nm. Th ese two classes of IONPs have been studied widely for medical applications, particularly as the next (potential) generation of MRI contrast agents. Th ey are also seen as potential vectors for drug and gene delivery. Th e biodistribution of these nanoparticles can be altered by the application of an external magnetic fi eld; they also have potential applications in hyperthermia therapy as some magnetic particles can heat up under the infl uence of a localized high-frequency magnetic fi eld.Th e intent of this review is to present recent advances in the synthesis of IONPs and their subsequent stabilization in biological fluids using polymers, focusing on the current strategies used to graft polymers onto IONPs surfaces (see Figure 1) and the diff erent types of polymers used. Th e additional properties conferred by the polymers, such as targeting, eff ects on biodistribution and pharmacokinetics, are also discussed, and the main applications of IONPs are reviewed. Synthesis and properties of iron-oxide nanoparticlesSPIO and USPIO nanoparticles are the most extensively studied magnetic nanoparticles for biomedical applications as they are both biocompatible and easy to synthesize. Both are composed of ferrite nanocrystallites of magnetite (Fe 3 O 4 ) or maghemite (Fe 2 O 3 , γ). Over the last ten years, there has been an explosion of interest in these materials and this has been reflected in a large number of recent publications describing the synthesis and modifi cation of hybrid IONPs. In this review, we focus on the polymer modifi cation of the nanoparticles, and provide only minimal information on the inorganic synthesis of IONPs. For more detailed information on IONP synthesis, readers are referred to other reviews [3,4]. The design and utility of polymer-stabilized iron-oxide nanoparticles for nanomedicine applicationsCyrille Boyer 1 * , Michael R. Whittaker 1 , Volga Bulmus 2 , Jingquan Liu 1 and Thomas P. Davis 1 * University of New South Wales, AustraliaOver the past decade, the synthesis of superparamagnetic nanoparticles, especially iron-oxide nanoparticles (IONPs), has been researched intensively for many high-technology applications, including enhanced storage media, biosensing and medical applications. In medicine, IONPs are used as contrast agents in magnetic resonance imaging and in hyperthermia...

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Section: Drug and Gene Deliverymentioning

confidence: 99%

The design and utility of polymer-stabilized iron-oxide nanoparticles for nanomedicine applications

et al. 2010

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“…The culture media were replaced with fresh medium containing nanogels diluted in complete medium and the cells were exposed to the nanogels for 24 h. Then, medium was replaced with complete medium without nanogels and the cell viability was evaluated using the MTT assay, essentially as previously described [31]. Briefly, MTT (3-(4,5-dimethyl-2-thiazoyl)-2,5-diphenyltetrazolium bromide, Roche, Mannheim, Germany, 250 μg/mL final concentration) was added to the cells for 2 h, then the cell culture supernatants were removed, the cell layers were dissolved in 2-propanol/ 0.04 N HCl and absorbance at 540 nm was measured (iEMS Reader MF, Labsystems, Bioconcept, Switzerland) and compared to the values of control cells incubated without nanogels.…”

Section: Determination Of Cytotoxicitymentioning

confidence: 99%

“…Briefly, MTT (3-(4,5-dimethyl-2-thiazoyl)-2,5-diphenyltetrazolium bromide, Roche, Mannheim, Germany, 250 μg/mL final concentration) was added to the cells for 2 h, then the cell culture supernatants were removed, the cell layers were dissolved in 2-propanol/ 0.04 N HCl and absorbance at 540 nm was measured (iEMS Reader MF, Labsystems, Bioconcept, Switzerland) and compared to the values of control cells incubated without nanogels. Alternatively for non-adherent human THP-1 macrophages, the alamarBlue assay was performed, as previously described [31]. Briefly, cells were exposed to 10% Alamar Blue (Serotec, Düsseldorf, Germany) added to the cell culture medium and fluorescence increase was directly measured in a multiwell fluorescence reader (λ ex /λ em =530 nm/580 nm) after 2 h at 37°C.…”

Section: Determination Of Cytotoxicitymentioning

confidence: 99%

Chitosan-based nanogels for selective delivery of photosensitizers to macrophages and improved retention in and therapy of articular joints

Schmitt

Lagopoulos

Käuper³

et al. 2010

Journal of Controlled Release

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112

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Macrophages play key roles in inflammatory disorders. Therefore, they are targets of treatments aiming at their local destruction in inflammation sites. However, injection of low molecular mass therapeutics, including photosensitizers, in inflamed joints results in their rapid efflux out of the joints, and poor therapeutic index. To improve selective uptake and increase retention of therapeutics in inflamed tissues, hydrophilic nanogels based on chitosan, of which surface was decorated with hyaluronate and which were loaded with one of three different anionic photosensitizers were developed. Optimal uptake of these functionalized nanogels by murine RAW 264.7 or human THP-1 macrophages as models was achieved after b 4 h incubation, whereas only negligible uptake by murine fibroblasts used as control cells was observed. The uptake by cells and the intracellular localization of the photosensitizers, of the fluorescein-tagged chitosan and of the rhodamine-tagged hyaluronate were confirmed by fluorescence microscopy. Photodynamic experiments revealed good cell photocytotoxicity of the photosensitizers entrapped in the nanogels. In a mouse model of rheumatoid arthritis, injection of free photosensitizers resulted in their rapid clearance from the joints, while nanogel-encapsulated photosensitizers were retained in the inflamed joints over a longer period of time. The photodynamic treatment of the inflamed joints resulted in a reduction of inflammation comparable to a standard corticoid treatment. Thus, hyaluronate-chitosan nanogels encapsulating therapeutic agents are promising materials for the targeted delivery to macrophages and long-term retention of therapeutics in leaky inflamed articular joints.

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“…Their experimental results showed a distinct pattern of Zeta potential change that allows the discrimination of normal human breast epithelial cells from breast cancer epithelial cells, where the tumor-homing F3 peptide was specifically bound to nucleolin receptors that are overexpressed in breast cancer cells. Cengelli et al [40] presented the linkage of therapeutic drugs to iron oxide nanoparticles, allowing the intracellular release of the active drug via cell-specific mechanisms. The drug-conjugated nanoparticles exhibited antiproliferative activity in vitro against human melanoma cells and resulted in tumor-selective and magnetically enhanced drug delivery.…”

Section: Iron Oxidesmentioning

confidence: 99%

“…Cengelli et al [40] demonstrated that a hierarchical building of a covalent drug-USPIO assembly is possible, even for highly hydrophobic drugs like camptothecin (CPT). The amount of CPT-USPIO taken up by human Me300 melanoma cells after 16 and 36 h as a function of the number of added nanoparticles was determined from the amount of cell-associated iron and cell-associated CPT fluorescence (figures 11(a) and (b)) as compared with that of the previously described aminoPVA-USPIOs [86].…”

Section: Inorganic Nanoparticles For Drug Deliverymentioning

confidence: 99%

Immobilization of biomolecules on the surface of inorganic nanoparticles for biomedical applications

Xing

Chang

Kang

2010

Science and Technology of Advanced Materials

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Various inorganic nanoparticles have been used for drug delivery, magnetic resonance and fluorescence imaging, and cell targeting owing to their unique properties, such as large surface area and efficient contrasting effect. In this review, we focus on the surface functionalization of inorganic nanoparticles via immobilization of biomolecules and the corresponding surface interactions with biocomponents. Applications of surface-modified inorganic nanoparticles in biomedical fields are also outlined.

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Surface‐Functionalized Ultrasmall Superparamagnetic Nanoparticles as Magnetic Delivery Vectors for Camptothecin

Abstract: Scheme 1. Reagents and conditions: a) camptothecin, EDC, DMAP, CH 2 Cl 2 , RT, o/n; b) TFA/CH 2 Cl 2 (1:1), RT, 40 min; c) EDC, HOBt, aminoPVA, DMF/H 2 O, RT, 1 d; d) ferrofluid.

Cited by 39 publications

References 31 publications

The design and utility of polymer-stabilized iron-oxide nanoparticles for nanomedicine applications

The design and utility of polymer-stabilized iron-oxide nanoparticles for nanomedicine applications

Chitosan-based nanogels for selective delivery of photosensitizers to macrophages and improved retention in and therapy of articular joints

Immobilization of biomolecules on the surface of inorganic nanoparticles for biomedical applications

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