Special Issue "Frontiers in Toxicity and Functionalization of Nanomaterials"

A special issue of Nanomaterials (ISSN 2079-4991).

Deadline for manuscript submissions: closed (30 September 2017)

Special Issue Editors

Guest Editor
Prof. Dr. Dong-Wook Han

College of Nanoscience & Nanotechnology, Pusan National University (PNU), Busandaehak-ro 63beon-gil 2, Geumjeong-gu, Busan 46241, Korea
Website | E-Mail
Interests: carbon-based nanomaterials; nanotoxicity; nanobioelectronics; nanomedicine; biocompatibility evaluation
Guest Editor
Dr. Wojciech Chrzanowski

Australian Institute of Nanoscale Science and Technology (Health and Medicine Theme Leader), Faculty of Pharmacy, The University of Sydney, Pharmacy and Bank Building A15, Camperdown, NSW 2006, Australia
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Interests: nanomedicine; biointefaces; nanomaterials; nanocharacterisation

Special Issue Information

Dear Colleagues,

Over the last decade, various nanomaterials (NMs) have attracted tremendous attention with the incredible development in nanoscience and nanotechnology. Some NMs are explored increasingly for biomedical applications including drug delivery carriers, imaging probes, antimicrobial agents, biosensors and tissue engineering scaffolds. However, the in vitro and in vivo toxicities of NMs related to oxidative stress are the main obstacles to use them in biomedical fields. One of the most promising strategies to address these obstacles is functionalizing NMs with biocompatible molecules or materials.

In this Special Issue, we are especially interested in manuscripts that advance the understanding of the interaction of NMs with cells, tissues, organs and systems as well as the relationship between intrinsic property and biocompatibility of NMs. This Special Issue invites manuscripts ranging from understanding all toxicological aspects, such as cytotoxicity, genotoxicity, hemotoxicity, neurotoxicity, immunotoxicity, histotoxicity and systemic toxicity of NMs. Manuscripts that focus on specific approaches and strategies to modify NMs with biofunctional moieties are also invited.

Prof. Dr. Dong-Wook Han
Dr. Wojciech Chrzanowski
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Nanomaterials is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1200 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • biomedical applications,
  • nanotoxicity,
  • cell-nanomaterial interactions,
  • biocompatibility,
  • nanomaterial functionalization

Published Papers (10 papers)

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Research

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Open AccessArticle Evaluation of MC3T3 Cells Proliferation and Drug Release Study from Sodium Hyaluronate-1,4-butanediol Diglycidyl Ether Patterned Gel
Nanomaterials 2017, 7(10), 328; doi:10.3390/nano7100328
Received: 18 September 2017 / Revised: 20 September 2017 / Accepted: 5 October 2017 / Published: 14 October 2017
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Abstract
A pattern gel has been fabricated using sodium hyaluronate (HA) and 1,4-butanediol diglycidyl ether (BDDGE) through the micro-molding technique. The cellular behavior of osteoblast cells (MC3T3) in the presence and absence of dimethyloxalylglycine (DMOG) and sodium borate (NaB) in the pattern gel (HA-BDDGE)
[...] Read more.
A pattern gel has been fabricated using sodium hyaluronate (HA) and 1,4-butanediol diglycidyl ether (BDDGE) through the micro-molding technique. The cellular behavior of osteoblast cells (MC3T3) in the presence and absence of dimethyloxalylglycine (DMOG) and sodium borate (NaB) in the pattern gel (HA-BDDGE) has been evaluated for its potential application in bone regeneration. The Fourier transform infrared spectroscopy (FTIR), 13C-nuclear magnetic resonance spectroscopy (13C NMR), and thermogravimetric analysis (TGA) results implied the crosslinking reaction between HA and BDDGE. The scanning electron microscopy (SEM) analysis confirmed the formation of pattern on the surface of HA-BDDGE. The gel property of the crosslinked HA-BDDGE has been investigated by swelling study in distilled water at 37 °C. The HA-BDDGE gel releases DMOG in a controlled way for up to seven days in water at 37 °C. The synthesized gel is biocompatible and the bolus drug delivery results indicated that the DMOG containing patterned gel demonstrates a better cell migration ability on the surface than NaB. For local delivery, the pattern gel with 300 µM NaB or 300 µM DMOG induced cell clusters formation, and the gel with 150 µM NaB/DMOG showed high cell proliferation capability only. The vital role of NaB for bone regeneration has been endorsed from the formation of cell clusters in presence of NaB in the media. The in vitro results indicated that the pattern gel showed angiogenic and osteogenic responses with good ALP activity and enhanced HIF-1α, and Runx2 levels in the presence of DMOG and NaB in MC3T3 cells. Hence, the HA-BDDGE gel could be used in bone regeneration application. Full article
(This article belongs to the Special Issue Frontiers in Toxicity and Functionalization of Nanomaterials)
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Open AccessArticle Room Temperature Tunable Multiferroic Properties in Sol-Gel-Derived Nanocrystalline Sr(Ti1−xFex)O3−δ Thin Films
Nanomaterials 2017, 7(9), 264; doi:10.3390/nano7090264
Received: 17 August 2017 / Revised: 2 September 2017 / Accepted: 5 September 2017 / Published: 8 September 2017
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Abstract
Sr(Ti1−xFex)O3−δ (0 ≤ x ≤ 0.2) thin films were grown on Si(100) substrates with LaNiO3 buffer-layer by a sol-gel process. Influence of Fe substitution concentration on the structural, ferroelectric, and magnetic properties, as well as the
[...] Read more.
Sr(Ti1−xFex)O3−δ (0 ≤ x ≤ 0.2) thin films were grown on Si(100) substrates with LaNiO3 buffer-layer by a sol-gel process. Influence of Fe substitution concentration on the structural, ferroelectric, and magnetic properties, as well as the leakage current behaviors of the Sr(Ti1−xFex)O3−δ thin films, were investigated by using the X-ray diffractometer (XRD), atomic force microscopy (AFM), the ferroelectric test system, and the vibrating sample magnetometer (VSM). After substituting a small amount of Ti ion with Fe, highly enhanced ferroelectric properties were obtained successfully in SrTi0.9Ti0.1O3−δ thin films, with a double remanent polarization (2Pr) of 1.56, 1.95, and 9.14 μC·cm−2, respectively, for the samples were annealed in air, oxygen, and nitrogen atmospheres. The leakage current densities of the Fe-doped SrTiO3 thin films are about 10−6–10−5 A·cm−2 at an applied electric field of 100 kV·cm−1, and the conduction mechanism of the thin film capacitors with various Fe concentrations has been analyzed. The ferromagnetic properties of the Sr(Ti1−xFex)O3−δ thin films have been investigated, which can be correlated to the mixed valence ions and the effects of the grain boundary. The present results revealed the multiferroic nature of the Sr(Ti1−xFex)O3−δ thin films. The effect of the annealing environment on the room temperature magnetic and ferroelectric properties of Sr(Ti0.9Fe0.1)O3−δ thin films were also discussed in detail. Full article
(This article belongs to the Special Issue Frontiers in Toxicity and Functionalization of Nanomaterials)
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Open AccessArticle The Effects of Silica Nanoparticles on Apoptosis and Autophagy of Glioblastoma Cell Lines
Nanomaterials 2017, 7(8), 230; doi:10.3390/nano7080230
Received: 15 July 2017 / Revised: 10 August 2017 / Accepted: 11 August 2017 / Published: 21 August 2017
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Abstract
Silica nanoparticles (SiNPs) are one of the most commonly used nanomaterials in various medical applications. However, possible mechanisms of the toxicity caused by SiNPs remain unclear. The study presented here provides novel information on molecular and cellular effects of SiNPs in glioblastoma LBC3
[...] Read more.
Silica nanoparticles (SiNPs) are one of the most commonly used nanomaterials in various medical applications. However, possible mechanisms of the toxicity caused by SiNPs remain unclear. The study presented here provides novel information on molecular and cellular effects of SiNPs in glioblastoma LBC3 and LN-18 cells. It has been demonstrated that SiNPs of 7 nm, 5–15 nm and 10–20 nm induce time- and dose-dependent cytotoxicity in LBC3 and LN-18 cell lines. In contrast to glioblastoma cells, we observed only weak reduction in viability of normal skin fibroblasts treated with SiNPs. Furthermore, in LBC3 cells treated with 5–15 nm SiNPs we noticed induction of apoptosis and necrosis, while in LN-18 cells only necrosis. The 5–15 nm SiNPs were also found to cause oxidative stress, a loss in mitochondrial membrane potential, and changes in the ultrastructure of the mitochondria in LBC3 cells. Quantitative real-time PCR results showed that in LBC3 cells the mRNA levels of pro-apoptotic genes Bim, Bax, Puma, and Noxa were significantly upregulated. An increase in activity of caspase-9 in these cells was also observed. Moreover, the activation of SiNP-induced autophagy was demonstrated in LBC3 cells as shown by an increase in LC3-II/LC3-I ratio, the upregulation of Atg5 gene and an increase in AVOs-positive cells. In conclusion, this research provides novel information concerning molecular mechanisms of apoptosis and autophagy in LBC3 cells. Full article
(This article belongs to the Special Issue Frontiers in Toxicity and Functionalization of Nanomaterials)
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Open AccessFeature PaperArticle Two-in-One Biointerfaces—Antimicrobial and Bioactive Nanoporous Gallium Titanate Layers for Titanium Implants
Nanomaterials 2017, 7(8), 229; doi:10.3390/nano7080229
Received: 10 July 2017 / Revised: 11 August 2017 / Accepted: 12 August 2017 / Published: 20 August 2017
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Abstract
The inhibitory effect of gallium (Ga) ions on bone resorption and their superior microbial activity are attractive and sought-after features for the vast majority of implantable devices, in particular for implants used for hard tissue. In our work, for the first time, Ga
[...] Read more.
The inhibitory effect of gallium (Ga) ions on bone resorption and their superior microbial activity are attractive and sought-after features for the vast majority of implantable devices, in particular for implants used for hard tissue. In our work, for the first time, Ga ions were successfully incorporated into the surface of titanium metal (Ti) by simple and cost-effective chemical and heat treatments. Ti samples were initially treated in NaOH solution to produce a nanostructured sodium hydrogen titanate layer approximately 1 μm thick. When the metal was subsequently soaked in a mixed solution of CaCl2 and GaCl3, its Na ions were replaced with Ca and Ga ions in a Ga/Ca ratio range of 0.09 to 2.33. 8.0% of the Ga ions were incorporated into the metal surface when the metal was soaked in a single solution of GaCl3 after the NaOH treatment. The metal was then heat-treated at 600 °C to form Ga-containing calcium titanate (Ga–CT) or gallium titanate (GT), anatase and rutile on its surface. The metal with Ga–CT formed bone-like apatite in a simulated body fluid (SBF) within 3 days, but released only 0.23 ppm of the Ga ions in a phosphate-buffered saline (PBS) over a period of 14 days. In contrast, Ti with GT did not form apatite in SBF, but released 2.96 ppm of Ga ions in PBS. Subsequent soaking in hot water at 80 °C dramatically enhanced apatite formation of the metal by increasing the release of Ga ions up to 3.75 ppm. The treated metal exhibited very high antibacterial activity against multidrug resistant Acinetobacter baumannii (MRAB12). Unlike other antimicrobial coating on titanium implants, Ga–CT and GT interfaces were shown to have a unique combination of antimicrobial and bioactive properties. Such dual activity is essential for the next generation of orthopaedic and dental implants. The goal of combining both functions without inducing cytotoxicity is a major advance and has far reaching translational perspectives. This unique dual-function biointerfaces will inhibit bone resorption and show antimicrobial activity through the release of Ga ions, while tight bonding to the bone will be achieved through the apatite formed on the surface. Full article
(This article belongs to the Special Issue Frontiers in Toxicity and Functionalization of Nanomaterials)
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Open AccessCommunication Toxicity and T2-Weighted Magnetic Resonance Imaging Potentials of Holmium Oxide Nanoparticles
Nanomaterials 2017, 7(8), 216; doi:10.3390/nano7080216
Received: 29 June 2017 / Revised: 15 July 2017 / Accepted: 2 August 2017 / Published: 7 August 2017
Cited by 1 | PDF Full-text (3083 KB) | HTML Full-text | XML Full-text
Abstract
In recent years, paramagnetic nanoparticles (NPs) have been widely used for magnetic resonance imaging (MRI). This paper reports the fabrication and toxicity evaluation of polyethylene glycol (PEG)-functionalized holmium oxide (Ho2O3) NPs for potential T2-weighted MRI applications. Various
[...] Read more.
In recent years, paramagnetic nanoparticles (NPs) have been widely used for magnetic resonance imaging (MRI). This paper reports the fabrication and toxicity evaluation of polyethylene glycol (PEG)-functionalized holmium oxide (Ho2O3) NPs for potential T2-weighted MRI applications. Various characterization techniques were used to examine the morphology, structure and chemical properties of the prepared PEG–Ho2O3 NPs. MRI relaxivity measurements revealed that PEG–Ho2O3 NPs could generate a strong negative contrast in T2-weighted MRI. The pilot cytotoxicity experiments showed that the prepared PEG–Ho2O3 NPs are biocompatible at concentrations less than 16 μg/mL. Overall, the prepared PEG–Ho2O3 NPs have potential applications for T2-weighted MRI imaging. Full article
(This article belongs to the Special Issue Frontiers in Toxicity and Functionalization of Nanomaterials)
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Open AccessArticle Antioxidant Potential and Antibacterial Efficiency of Caffeic Acid-Functionalized ZnO Nanoparticles
Nanomaterials 2017, 7(6), 148; doi:10.3390/nano7060148
Received: 2 May 2017 / Revised: 13 June 2017 / Accepted: 14 June 2017 / Published: 16 June 2017
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Abstract
We report a novel zinc oxide (ZnO) nanoparticle with antioxidant properties, prepared by immobilizing the antioxidant 3-(3,4-dihydroxyphenyl)-2-propenoic acid (caffeic acid, CA) on the surfaces of micro-dielectric barrier discharge (DBD) plasma-treated ZnO nanoparticles. The microstructure and physical properties of ZnO@CA nanoparticles were characterized by
[...] Read more.
We report a novel zinc oxide (ZnO) nanoparticle with antioxidant properties, prepared by immobilizing the antioxidant 3-(3,4-dihydroxyphenyl)-2-propenoic acid (caffeic acid, CA) on the surfaces of micro-dielectric barrier discharge (DBD) plasma-treated ZnO nanoparticles. The microstructure and physical properties of ZnO@CA nanoparticles were characterized by field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), infrared spectroscopy, and steady state spectroscopic methods. The antioxidant activity of ZnO@CA nanoparticles was evaluated using an ABTS (3-ethyl-benzothiazoline-6-sulfonic acid) radical cation decolorization assay. ZnO@CA nanoparticles exhibited robust antioxidant activity. Moreover, ZnO@CA nanoparticles showed strong antibacterial activity against Gram-positive bacteria (Staphylococcus aureus) including resistant bacteria such as methicillin-resistant S. aureus and against Gram-negative bacteria (Escherichia coli). Although Gram-negative bacteria appeared to be more resistant to ZnO@CA nanoparticles than Gram-positive bacteria, the antibacterial activity of ZnO@CA nanoparticles was dependent on particle concentration. The antioxidant and antibacterial activity of ZnO@CA may be useful for various biomedical and nanoindustrial applications. Full article
(This article belongs to the Special Issue Frontiers in Toxicity and Functionalization of Nanomaterials)
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Open AccessArticle Optimized Photodynamic Therapy with Multifunctional Cobalt Magnetic Nanoparticles
Nanomaterials 2017, 7(6), 144; doi:10.3390/nano7060144
Received: 2 May 2017 / Revised: 24 May 2017 / Accepted: 7 June 2017 / Published: 10 June 2017
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Abstract
Photodynamic therapy (PDT) has been adopted as a minimally invasive approach for the localized treatment of superficial tumors, representing an improvement in the care of cancer patients. To improve the efficacy of PDT, it is important to first select an optimized nanocarrier and
[...] Read more.
Photodynamic therapy (PDT) has been adopted as a minimally invasive approach for the localized treatment of superficial tumors, representing an improvement in the care of cancer patients. To improve the efficacy of PDT, it is important to first select an optimized nanocarrier and determine the influence of light parameters on the photosensitizing agent. In particular, much more knowledge concerning the importance of fluence and exposure time is required to gain a better understanding of the photodynamic efficacy. In the present study, we synthesized novel folic acid-(FA) and hematoporphyrin (HP)-conjugated multifunctional magnetic nanoparticles (CoFe2O4-HPs-FAs), which were characterized as effective anticancer reagents for PDT, and evaluated the influence of incubation time and light exposure time on the photodynamic anticancer activities of CoFe2O4-HPs-FAs in prostate cancer cells (PC-3 cells). The results indicated that the same fluence at different exposure times resulted in changes in the anticancer activities on PC-3 cells as well as in reactive oxygen species formation. In addition, an increase of the fluence showed an improvement for cell photo-inactivation. Therefore, we have established optimized conditions for new multifunctional magnetic nanoparticles with direct application for improving PDT for cancer patients. Full article
(This article belongs to the Special Issue Frontiers in Toxicity and Functionalization of Nanomaterials)
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Open AccessArticle Cellular Response to Titanium Dioxide Nanoparticles in Intestinal Epithelial Caco-2 Cells is Dependent on Endocytosis-Associated Structures and Mediated by EGFR
Nanomaterials 2017, 7(4), 79; doi:10.3390/nano7040079
Received: 3 March 2017 / Revised: 5 April 2017 / Accepted: 5 April 2017 / Published: 7 April 2017
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Abstract
Titanium dioxide (TiO2) is one of the most applied nanomaterials and widely used in food and non-food industries as an additive or coating material (E171). It has been shown that E171 contains up to 37% particles which are smaller than 100
[...] Read more.
Titanium dioxide (TiO2) is one of the most applied nanomaterials and widely used in food and non-food industries as an additive or coating material (E171). It has been shown that E171 contains up to 37% particles which are smaller than 100 nm and that TiO2 nanoparticles (NPs) induce cytotoxicity and inflammation. Using a nuclear factor Kappa-light-chain enhancer of activated B cells (NF-κB) reporter cell line (Caco-2nfkb-RE), Real time polymerase chain reaction (PCR), and inhibition of dynamin and clathrin, it was shown that cellular responses induced by 5 nm and 10 nm TiO2 NPs (nominal size) depends on endocytic processes. As endocytosis is often dependent on the epithelial growth factor receptor (EGFR), further investigations focused on the involvement of EGFR in the uptake of TiO2 NPs: (1) inhibition of EGFR reduced inflammatory markers of the cell (i.e., nuclear factor (NF)-κB activity, mRNA of IL8, CCL20, and CXCL10); and (2) exposure of Caco-2 cells to TiO2 NPs activated the intracellular EGFR cascade beginning with EGFR-mediated extracellular signal-regulated kinases (ERK)1/2, and including transcription factor ELK1. This was followed by the expression of ERK1/2 target genes CCL2 and CXCL3. We concluded that TiO2 NPs enter the cell via EGFR-associated endocytosis, followed by activation of the EGFR/ERK/ELK signaling pathway, which finally induces NF-κB. No changes in inflammatory response are observed in Caco-2 cells exposed to 32 nm and 490 nm TiO2 particles. Full article
(This article belongs to the Special Issue Frontiers in Toxicity and Functionalization of Nanomaterials)
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Open AccessArticle Eu, Gd-Codoped Yttria Nanoprobes for Optical and T1-Weighted Magnetic Resonance Imaging
Nanomaterials 2017, 7(2), 35; doi:10.3390/nano7020035
Received: 13 December 2016 / Revised: 26 January 2017 / Accepted: 3 February 2017 / Published: 10 February 2017
Cited by 3 | PDF Full-text (2359 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Nanoprobes with multimodal functionality have attracted significant interest recently because of their potential applications in nanomedicine. This paper reports the successful development of lanthanide-doped Y2O3 nanoprobes for potential applications in optical and magnetic resonance (MR) imaging. The morphology, structural, and
[...] Read more.
Nanoprobes with multimodal functionality have attracted significant interest recently because of their potential applications in nanomedicine. This paper reports the successful development of lanthanide-doped Y2O3 nanoprobes for potential applications in optical and magnetic resonance (MR) imaging. The morphology, structural, and optical properties of these nanoprobes were characterized by transmission electron microscope (TEM), field emission scanning electron microscope (FESEM), X-ray diffraction (XRD), energy-dispersive X-ray (EDX), and photoluminescence (PL). The cytotoxicity test showed that the prepared lanthanide-doped Y2O3 nanoprobes have good biocompatibility. The obvious contrast enhancement in the T1-weighted MR images suggested that these nanoprobes can be used as a positive contrast agent in MRI. In addition, the clear fluorescence images of the L-929 cells incubated with the nanoprobes highlight their potential for optical imaging. Overall, these results suggest that prepared lanthanide-doped Y2O3 nanoprobes can be used for simultaneous optical and MR imaging. Full article
(This article belongs to the Special Issue Frontiers in Toxicity and Functionalization of Nanomaterials)
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Review

Jump to: Research

Open AccessReview Mesoporous Silica Nanoparticles as Drug Delivery Vehicles in Cancer
Nanomaterials 2017, 7(7), 189; doi:10.3390/nano7070189
Received: 13 June 2017 / Revised: 14 July 2017 / Accepted: 18 July 2017 / Published: 22 July 2017
Cited by 2 | PDF Full-text (3194 KB) | HTML Full-text | XML Full-text
Abstract
Even though cancer treatment has improved over the recent decades, still more specific and effective treatment concepts are mandatory. Surgical removal is not always possible, metastases are challenging and chemo- and radiotherapy can not only have severe side-effects but also resistances may occur.
[...] Read more.
Even though cancer treatment has improved over the recent decades, still more specific and effective treatment concepts are mandatory. Surgical removal is not always possible, metastases are challenging and chemo- and radiotherapy can not only have severe side-effects but also resistances may occur. To cope with these challenges more efficient therapies with fewer side-effects are required. One promising approach is the use of drug delivery vehicles. Here, mesoporous silica nanoparticles (MSN) are discussed as biodegradable drug carrier to improve efficacy and reduce side-effects. MSN excellently fulfill the criteria for nanoparticulate carriers: their distinct structure allows high loading capacity and a plethora of surface modifications. MSN synthesis permits fine-tuning of particle and pore sizes. Moreover, drug release can be tailored through various gatekeeper systems which are for example pH-sensitive or redox-sensitive. Furthermore, MSN can either enter tumors passively by the enhanced permeability and retention effect or can be actively targeted by various ligands. PEGylation prolongs circulation time and availability. A huge advantage of MSN is their explicitly low toxic profile in vivo. Yet, clinical translation remains challenging. Overall, mesoporous silica nanoparticles are a promising tool for innovative, more efficient and safer cancer therapies. Full article
(This article belongs to the Special Issue Frontiers in Toxicity and Functionalization of Nanomaterials)
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