Nanomaterials for Biosensing, Bioimaging and Therapy: From Cancer to Alzheimer's Disease

A special issue of Nanomaterials (ISSN 2079-4991). This special issue belongs to the section "Biology and Medicines".

Deadline for manuscript submissions: closed (30 June 2021) | Viewed by 30981

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Guest Editor
Department of Chemistry, Myongji University, Yongin 449-728, Republic of Korea
Interests: nanoparticles; quantum dots; multifunctional nanoparticles; bioimaging; biosensing; drug delivery; neurodegenerative nanomedicine; batteries; solar cells
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Special Issue Information

Dear Colleagues,

Biosensing and bioimaging are two key technological areas that are highly indispensable for the next generation of point-of-care devices. Targeted drug delivery and therapy is another emerging paradigm in the field of theranostic nanomedicine. This Special Issue attempts to garner advances in these three areas (imaging, sensing, and therapy) with the advent of nanotechnology for both cancer and neurodegenerative diseases (Alzheimer's disease (AD) and Parkinson's).  

Nanomaterials, in particular nanoparticles (NPs), have been widely used for biosensing, bioimaging and targeted drug delivery in various disease models. Typical examples of NPs include plasmonic Au; CdSe/ZnS, carbon, graphene quantum dots (QDs); magnetic NPs; upconversion NPs; and transition-metal ion-doped QDs. Functionalized NPs with antibodies, peptides, oligonucleotides are generally used for specific targeting of cells and animal tissues.

This Special Issue will focus on recent advances in various nanomaterials and NPs that can be used as probes for sensing (e.g., protein detection, fluorescence resonance energy transfer (FRET) biosensors) and imaging (cancer and Alzheimer's disease cell/animal imaging), using optical imaging, magnetic resonance imaging (MRI), computed tomography (CT), and other multimodal imaging techniques, and NPs as drug vehicles for targeted delivery and therapy.

Topic to be covered (but not limited to the following):

  • Nanomaterials for cancer and neurodegenerative diseases (Parkinson's or Alzheimer's)
  • Quantum dots for in-vitro cell and in-vivo animal imaging of tumors
  • Bio-functionalized quantum dots with prostate-specific membrane antigen, Her2, EGFR for prostate and breast cancer diagnostics, and Alzheimer's disease
  • Transition-metal ion-doped QDs for biosensing and bioimaging
  • Lanthanide-doped upconversion NPs for imaging and therapy of cancer and Alzheimer's disease
  • Nanoparticles as contrast agents for CT/MRI and multimodal imaging
  • Nanoparticles for photothermal therapy of cancer
  • Surface-enhanced Raman scattering (SERS) plasmonic nanosensors for pH monitoring in single cells and detection of specific genes for diseases
  • Plasmonic nanosensors for cellular biosensing, diagnostics and high throughput screening
  • Nanoparticles for the detection of specific target DNA sequences associated with diseases

Prof. Dr. Subramanian Tamil Selvan
Guest Editor

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Keywords

  • Nanomedicine
  • Nanoparticles
  • Cancer
  • Alzheimer's disease (AD)
  • Biosensing
  • Bioimaging
  • FRET sensing
  • Multimodal imaging

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Published Papers (6 papers)

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Research

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19 pages, 3984 KiB  
Article
Synergy of Chemo- and Photodynamic Therapies with C60 Fullerene-Doxorubicin Nanocomplex
by Anna Grebinyk, Svitlana Prylutska, Oksana Chepurna, Sergii Grebinyk, Yuriy Prylutskyy, Uwe Ritter, Tymish Y. Ohulchanskyy, Olga Matyshevska, Thomas Dandekar and Marcus Frohme
Nanomaterials 2019, 9(11), 1540; https://doi.org/10.3390/nano9111540 - 30 Oct 2019
Cited by 36 | Viewed by 4408
Abstract
A nanosized drug complex was explored to improve the efficiency of cancer chemotherapy, complementing it with nanodelivery and photodynamic therapy. For this, nanomolar amounts of a non-covalent nanocomplex of Doxorubicin (Dox) with carbon nanoparticle C60 fullerene (C60) were applied in [...] Read more.
A nanosized drug complex was explored to improve the efficiency of cancer chemotherapy, complementing it with nanodelivery and photodynamic therapy. For this, nanomolar amounts of a non-covalent nanocomplex of Doxorubicin (Dox) with carbon nanoparticle C60 fullerene (C60) were applied in 1:1 and 2:1 molar ratio, exploiting C60 both as a drug-carrier and as a photosensitizer. The fluorescence microscopy analysis of human leukemic CCRF-CEM cells, in vitro cancer model, treated with nanocomplexes showed Dox’s nuclear and C60’s extranuclear localization. It gave an opportunity to realize a double hit strategy against cancer cells based on Dox’s antiproliferative activity and C60’s photoinduced pro-oxidant activity. When cells were treated with 2:1 C60-Dox and irradiated at 405 nm the high cytotoxicity of photo-irradiated C60-Dox enabled a nanomolar concentration of Dox and C60 to efficiently kill cancer cells in vitro. The high pro-oxidant and pro-apoptotic efficiency decreased IC50 16, 9 and 7 × 103-fold, if compared with the action of Dox, non-irradiated nanocomplex, and C60’s photodynamic effect, correspondingly. Hereafter, a strong synergy of therapy arising from the combination of C60-mediated Dox delivery and C60 photoexcitation was revealed. Our data indicate that a combination of chemo- and photodynamic therapies with C60-Dox nanoformulation provides a promising synergetic approach for cancer treatment. Full article
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12 pages, 1214 KiB  
Article
Lights Out! Nano-Scale Topography Imaging of Sample Surface in Opaque Liquid Environments with Coated Active Cantilever Probes
by Fangzhou Xia, Chen Yang, Yi Wang, Kamal Youcef-Toumi, Christoph Reuter, Tzvetan Ivanov, Mathias Holz and Ivo W. Rangelow
Nanomaterials 2019, 9(7), 1013; https://doi.org/10.3390/nano9071013 - 14 Jul 2019
Cited by 9 | Viewed by 3627
Abstract
Atomic force microscopy is a powerful topography imaging method used widely in nanoscale metrology and manipulation. A conventional Atomic Force Microscope (AFM) utilizes an optical lever system typically composed of a laser source, lenses and a four quadrant photodetector to amplify and measure [...] Read more.
Atomic force microscopy is a powerful topography imaging method used widely in nanoscale metrology and manipulation. A conventional Atomic Force Microscope (AFM) utilizes an optical lever system typically composed of a laser source, lenses and a four quadrant photodetector to amplify and measure the deflection of the cantilever probe. This optical method for deflection sensing limits the capability of AFM to obtaining images in transparent environments only. In addition, tapping mode imaging in liquid environments with transparent sample chamber can be difficult for laser-probe alignment due to multiple different refraction indices of materials. Spurious structure resonance can be excited from piezo actuator excitation. Photothermal actuation resolves the resonance confusion but makes optical setup more complicated. In this paper, we present the design and fabrication method of coated active scanning probes with piezoresistive deflection sensing, thermomechanical actuation and thin photoresist polymer surface coating. The newly developed probes are capable of conducting topography imaging in opaque liquids without the need of an optical system. The selected coating can withstand harsh chemical environments with high acidity (e.g., 35% sulfuric acid). The probes are operated in various opaque liquid environments with a custom designed AFM system to demonstrate the imaging performance. The development of coated active probes opens up possibilities for observing samples in their native environments. Full article
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27 pages, 2884 KiB  
Article
The Impact of Nylon-3 Copolymer Composition on the Efficiency of siRNA Delivery to Glioblastoma Cells
by Natascha Hartl, Friederike Adams, Gabriella Costabile, Lorenz Isert, Markus Döblinger, Ximian Xiao, Runhui Liu and Olivia M. Merkel
Nanomaterials 2019, 9(7), 986; https://doi.org/10.3390/nano9070986 - 8 Jul 2019
Cited by 17 | Viewed by 5277
Abstract
Glioblastoma multiforme is a devastating disease that has attracted enormous attention due to poor prognosis and high recurrence. Small interfering RNA (siRNA) in principle offers a promising therapeutic approach by the downregulation of disease-related genes via RNA interference. For efficient siRNA delivery to [...] Read more.
Glioblastoma multiforme is a devastating disease that has attracted enormous attention due to poor prognosis and high recurrence. Small interfering RNA (siRNA) in principle offers a promising therapeutic approach by the downregulation of disease-related genes via RNA interference. For efficient siRNA delivery to target sites, cationic polymers are often used in preclinical studies for the protection of siRNA and complex formation based on electrostatic interactions. In an effort to develop biocompatible and efficient nanocarriers with a translational outlook for optimal gene silencing at reduced toxicity, we synthesized two sets of nylon-3 copolymers with variable cationic content (DM or NM monomer) and hydrophobic subunits (CP monomer) and evaluated their suitability for in vitro siRNA delivery into glioblastoma cells. DM0.4/CP0.6 and NM0.4/CP0.6 polymers with similar subunit ratios were synthesized to compare the effect of different cationic subunits. Additionally, we utilized NM0.2/CP0.8 polymers to evaluate the impact of the different hydrophobic content in the polymer chain. The siRNA condensation ability and polymer–siRNA complex stability was evaluated by unmodified and modified SYBR gold assays, respectively. Further physicochemical characteristics, e.g., particle size and surface charge, were evaluated by dynamic light scattering and laser Doppler anemometry, whereas a relatively new method for polyplex size distribution analysis—tunable resistive pulse sensing—was additionally developed and compared to DLS measurements. Transfection efficiencies, the route of cell internalization, and protein knockdown abilities in glioblastoma cells were investigated by flow cytometry. Furthermore, cellular tolerability was evaluated by MTT and LDH assays. All the polymers efficiently condensed siRNA at N/P ratios of three, whereas polymers with NM cationic subunits demonstrated smaller particle size and lower polyplex stability. Furthermore, NM0.2/CP0.8 polyplexes with the highest hydrophobic content displayed significantly higher cellular internalization in comparison to more cationic formulations and successful knockdown capabilities. Detailed investigations of the cellular uptake route demonstrated that these polyplexes mainly follow clathrin-mediated endocytotic uptake mechanisms, implying high interaction capacity with cellular membranes. Taken together with conducive toxicity profiles, highly hydrophobic nylon-3 polymers provide an appropriate siRNA delivery agent for the potential treatment of glioblastoma. Full article
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14 pages, 1610 KiB  
Article
Drug Exchange between Albumin Nanoparticles and Erythrocyte Membranes
by Bilyana Tacheva, Boyana Paarvanova, Ivan T. Ivanov, Boris Tenchov, Radostina Georgieva and Miroslav Karabaliev
Nanomaterials 2019, 9(1), 47; https://doi.org/10.3390/nano9010047 - 31 Dec 2018
Cited by 8 | Viewed by 4252
Abstract
The effects of thioridazine (TDZ) and chlorpromazine (CPZ) and bovine serum albumin nanoparticles (BSA-NPs) on erythrocyte membranes have been investigated. Two kinds of hemolytic assays were used; hemolysis under hypotonic conditions and hemolysis in physiological conditions. Under hypotonic conditions for 50% hemolysis, both [...] Read more.
The effects of thioridazine (TDZ) and chlorpromazine (CPZ) and bovine serum albumin nanoparticles (BSA-NPs) on erythrocyte membranes have been investigated. Two kinds of hemolytic assays were used; hemolysis under hypotonic conditions and hemolysis in physiological conditions. Under hypotonic conditions for 50% hemolysis, both TDZ and CPZ have a biphasic effect on membranes; namely, stabilization at low concentrations and destabilization after reaching a critical concentration. In physiological conditions, there are other critical concentrations above which both drugs hemolyse the erythrocites. In each case, the critical concentrations of TDZ are lower than those of CPZ, which is consistent with the ratio of their partition coefficients. When BSA-NPs are added to the erythrocyte suspension simultaneously with the drugs, the critical concentrations increase for both drugs. The effect is due to the incorporation of a portion of drug substances into the BSA-nanoparticles, which consequently leads to the decrease of the active drug concentrations in the erythrocyte suspension medium. Similar values of the critical concentrations are found when the BSA-NPs are loaded with the drugs before their addition to the erythrocyte suspension in which case the events of the partition are: desorption of the drug from BSA-NPs, diffusion through the medium, and adsorption on erythrocyte membranes. This result suggests that the drugs are not influenced by the processes of adsorption and desorption onto and out of the BSA-NPs, and that the use of BSA-NPs as drug transporters would allow intravenous administration of higher doses of the drug without the risk of erythrocyte hemolysis. Full article
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18 pages, 29876 KiB  
Article
Graphene Oxide/ZnS:Mn Nanocomposite Functionalized with Folic Acid as a Nontoxic and Effective Theranostic Platform for Breast Cancer Treatment
by Daysi Diaz-Diestra, Bibek Thapa, Dayra Badillo-Diaz, Juan Beltran-Huarac, Gerardo Morell and Brad R. Weiner
Nanomaterials 2018, 8(7), 484; https://doi.org/10.3390/nano8070484 - 30 Jun 2018
Cited by 40 | Viewed by 7260
Abstract
Nanoparticle-based cancer theranostic agents generally suffer of poor dispersability in biological media, re-agglomeration over time, and toxicity concerns. To address these challenges, we developed a nanocomposite consisting of chemically-reduced graphene oxide combined with manganese-doped zinc sulfide quantum dots and functionalized with folic acid [...] Read more.
Nanoparticle-based cancer theranostic agents generally suffer of poor dispersability in biological media, re-agglomeration over time, and toxicity concerns. To address these challenges, we developed a nanocomposite consisting of chemically-reduced graphene oxide combined with manganese-doped zinc sulfide quantum dots and functionalized with folic acid (FA-rGO/ZnS:Mn). We studied the dispersion stability, Doxorubicin (DOX) loading and release efficiency, target specificity, internalization, and biocompatibility of FA-rGO/ZnS:Mn against folate-rich breast cancer cells, and compared to its uncoated counterpart (rGO/ZnS:Mn). The results indicate that DOX is adsorbed on the graphene surface via π–π stacking and hydrophobic interaction, with enhanced loading (~35%) and entrapment (~60%) efficiency that are associated to the chelation of DOX and surface Zn2+ ions. DOX release is favored under acidic conditions reaching a release of up to 95% after 70 h. Membrane integrity of the cells assessed by Lactate dehydrogenase (LDH) release indicate that the surface passivation caused by folic acid (FA) functionalization decreases the strong hydrophobic interaction between the cell membrane wall and the edges/corners of graphene flakes. Chemotherapeutic effect assays reveal that the cancer cell viability was reduced up to ~50% at 3 µg/mL of DOX-FA-rGO/ZnS:Mn exposure, which is more pronounced than those obtained for free DOX at the same doses. Moreover, DOX-rGO/ZnS:Mn did not show any signs of toxicity. An opposite trend was observed for cells that do not overexpress the folate receptors, indicating that FA functionalization endows rGO/ZnS:Mn with an effective ability to discriminate positive folate receptor cancerous cells, enhancing its drug loading/release efficiency as a compact drug delivery system (DDS). This study paves the way for the potential use of functionalized rGO/ZnS:Mn nanocomposite as a platform for targeted cancer treatment. Full article
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Review

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23 pages, 935 KiB  
Review
Contrast Agents Delivery: An Up-to-Date Review of Nanodiagnostics in Neuroimaging
by Daniel Mihai Teleanu, Cristina Chircov, Alexandru Mihai Grumezescu, Adrian Volceanov and Raluca Ioana Teleanu
Nanomaterials 2019, 9(4), 542; https://doi.org/10.3390/nano9040542 - 3 Apr 2019
Cited by 24 | Viewed by 5125
Abstract
Neuroimaging is a highly important field of neuroscience, with direct implications for the early diagnosis and progression monitoring of brain-associated diseases. Neuroimaging techniques are categorized into structural, functional and molecular neuroimaging, each possessing advantages and disadvantages in terms of resolution, invasiveness, toxicity of [...] Read more.
Neuroimaging is a highly important field of neuroscience, with direct implications for the early diagnosis and progression monitoring of brain-associated diseases. Neuroimaging techniques are categorized into structural, functional and molecular neuroimaging, each possessing advantages and disadvantages in terms of resolution, invasiveness, toxicity of contrast agents and costs. Nanotechnology-based approaches for neuroimaging mostly involve the development of nanocarriers for incorporating contrast agents or the use of nanomaterials as imaging agents. Inorganic and organic nanoparticles, liposomes, micelles, nanobodies and quantum dots are some of the most studied candidates for the delivery of contrast agents for neuroimaging. This paper focuses on describing the conventional modalities used for imaging and the applications of nanotechnology for developing novel strategies for neuroimaging. The aim is to highlight the roles of nanocarriers for enhancing and/or overcome the limitations associated with the most commonly utilized neuroimaging modalities. For future directions, several techniques that could benefit from the increased contrast induced by using imaging probes are presented. Full article
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