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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (30 June 2018) | Viewed by 65947

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Dr. Tuhin Subhra Santra

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Guest Editor

Department of Engineering Design, Indian Institute of Technology Madras, Chennai, India
Interests: MEMS; Bio-NEMS; single- cell technology; biomedical micro/nano devices; micro/nanofluidics; nanomedicine
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Fan-Gang Tseng

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Guest Editor

Distinguished Professor, Department of Engineering and System Science, National Tsing Hua University (NTHU), Affiliated Research Fellow, Academia Sinica, Hsinchu, Taiwan
Interests: organ on a chip; microfluidic systems; biosensors; CTCs/CTM diagnosis; single cell analysis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

“Human health has always been determined on the nanometer scale; this is where the structure and properties of the machines of life work in every one of the cells in every living thing. The practical impact of nanoscience on human health will be huge” (Dr. Richard E. Smalley, 1996 Nobel laurate). Nanomedicine or molecular medicine is the combination of nanoscience and nanotechnology, chemistry and life science, which has tremendous application in solving human health problem including diseases diagnosis, imaging, monitoring and therapy.

This Special Issue invites the latest research articles and reviews concerning the role of nanoscience and nanotechnology in life science, prospect of nanomedicine or molecular medicine, nanotechnology for drug delivery, therapy, diagnostics, treatment, prediction and prevention of different diseases, potential medical nanoscience advances, nanomaterial and nanoparticles in nanomedicine, clinical applications of nanomedicine, regenerative medicine, tissue regeneration, biomimetics, bioinformatics, etc.

This Special Issue is cooperating with the international conference MicroTAS 2017 (https://www.microtas2017.org/). All speakers presenting a paper at this conference can submit a manuscript for publication.

Assis. Prof. Dr. Tuhin Subhra Santra
Prof. Dr. Fan-Gang Tseng
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 submissions that pass pre-check are 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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

Nanotechnology in life science
Nanomaterial and nanoparticles in nanomedicine
Imaging
Bio-nanomaterial
Nanoparticles interaction with cells and tissues
Nanostructured for tissue regeneration, antimicrobial
Drug delivery, diagnostics, therapy
Medical nanoscience
Point of care diagnostics
Clinical applications of nanomedicine
Regenerative medicine
Biomedical micro/nano devices for cellular therapy and analysis
Single cell technology
Single molecule detection
Tissue regeneration
Biomimetics

Published Papers (10 papers)

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Research

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14 pages, 3247 KiB

Open AccessArticle

Inhibition of Experimental Choroidal Neovascularization by a Novel Peptide Derived from Calreticulin Anti-Angiogenic Domain

by Youn-Shen Bee, Yi-Ling Ma, Jinying Chen, Pei-Jhen Tsai, Shwu-Jiuan Sheu, Hsiu-Chen Lin, Hu Huang, Guei-Sheung Liu and Ming-Hong Tai

Int. J. Mol. Sci. 2018, 19(10), 2993; https://doi.org/10.3390/ijms19102993 - 30 Sep 2018

Cited by 6 | Viewed by 3838

Abstract

Choroidal neovascularization (CNV) is a key pathological feature of several leading causes of vision loss including neovascular age-related macular degeneration. Here, we show that a calreticulin anti-angiogenic domain (CAD)-like peptide 27, CAD27, inhibited in vitro angiogenic activities, including tube formation, migration of endothelial cells, and vascular sprouting from rat aortic ring explants. In a rat model of laser-induced CNV, we demonstrate that intravitreal injection of CAD27 significantly attenuated the formation of CNV lesions as measured via fundus fluorescein angiography and choroid flat-mounts (19.5% and 22.4% reductions at 10 μg and 20 μg of CAD27 injected, respectively). Similarly, the reduction of CNV lesions was observed in rats that had received topical applications of CAD27 (choroid flat-mounts: 17.9% and 32.5% reductions at 10 μg/mL and 20 μg/mL of CAD27 instilled, respectively). Retinal function was unaffected, as measured using electroretinography in both groups receiving interareal injection or topical applications of CAD27 for at least fourteen days. These findings show that CAD27 can be used as a potential therapeutic alternative for targeting CNV in diseases such as neovascular age-related macular degeneration. Full article

(This article belongs to the Special Issue Nanomedicine/Molecular Medicine)

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17 pages, 5095 KiB

Open AccessArticle

Increased Oral Bioavailability of Resveratrol by Its Encapsulation in Casein Nanoparticles

by Rebeca Peñalva, Jorge Morales, Carlos J. González-Navarro, Eneko Larrañeta, Gemma Quincoces, Ivan Peñuelas and Juan M. Irache

Int. J. Mol. Sci. 2018, 19(9), 2816; https://doi.org/10.3390/ijms19092816 - 18 Sep 2018

Cited by 117 | Viewed by 7063

Abstract

Resveratrol is a naturally occurring polyphenol that provides several health benefits including cardioprotection and cancer prevention. However, its biological activity is limited by a poor bioavailability when taken orally. The aim of this work was to evaluate the capability of casein nanoparticles as oral carriers for resveratrol. Nanoparticles were prepared by a coacervation process, purified and dried by spray-drying. The mean size of nanoparticles was around 200 nm with a resveratrol payload close to 30 μg/mg nanoparticle. In vitro studies demonstrated that the resveratrol release from casein nanoparticles was not affected by the pH conditions and followed a zero-order kinetic. When nanoparticles were administered orally to rats, they remained within the gut, displaying an important capability to reach the intestinal epithelium. No evidence of nanoparticle “translocation” were observed. The resveratrol plasma levels were high and sustained for at least 8 h with a similar profile to that observed for the presence of the major metabolite in plasma. The oral bioavailability of resveratrol when loaded in casein nanoparticles was calculated to be 26.5%, 10 times higher than when the polyphenol was administered as oral solution. Finally, a good correlation between in vitro and in vivo data was observed. Full article

(This article belongs to the Special Issue Nanomedicine/Molecular Medicine)

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12 pages, 7148 KiB

Open AccessArticle

Ex Vivo and in Vivo Study of Sucrosomial^® Iron Intestinal Absorption and Bioavailability

by Angela Fabiano, Elisa Brilli, Letizia Mattii, Lara Testai, Stefania Moscato, Valentina Citi, Germano Tarantino and Ylenia Zambito

Int. J. Mol. Sci. 2018, 19(9), 2722; https://doi.org/10.3390/ijms19092722 - 12 Sep 2018

Cited by 25 | Viewed by 5342

Abstract

The present study aimed to demonstrate that Sideral^® RM (SRM, Sucrosomial^® Raw Material Iron) is transported across the excised intestine via a biological mechanism, and to investigate the effect that this transport route may produce on oral iron absorption, which is expected to reduce the gastrointestinal (GI) side effects caused by the bioavailability of non-absorbed iron. Excised rat intestine was exposed to fluorescein isothiocyanate (FITC)-labeled SRM in Ussing chambers followed by confocal laser scanning microscopy to look for the presence of fluorescein-tagged vesicles of the FITC-labeled SRM. To identify FITC-labeled SRM internalizing cells, an immunofluorescence analysis for macrophages and M cells was performed using specific antibodies. Microscopy analysis revealed the presence of fluorescein positive particulate structures in tissues treated with FITC-labeled SRM. These structures do not disintegrate during transit, and concentrate in macrophage cells. Iron bioavailability was assessed by determining the time-course of Fe³⁺ plasma levels. As references, iron contents in liver, spleen, and bone marrow were determined in healthy rats treated by gavage with SRM or ferric pyrophosphate salt (FP). SRM significantly increased both area under the curve (AUC) and clearance maxima (C_max) compared to FP, thus increasing iron bioavailability (AUC_rel = 1.8). This led to increased iron availability in the bone marrow at 5 h after single dose gavage. Full article

(This article belongs to the Special Issue Nanomedicine/Molecular Medicine)

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15 pages, 5946 KiB

Open AccessArticle

Extract of the Blood Circulation-Promoting Recipe-84 Can Protect Rat Retinas by Inhibiting the β-Catenin Signaling Pathway

by Qiu-Fang Qin, Min Liu, Gui-Hua Tian, Jian Chen and Yu-Sang Li

Int. J. Mol. Sci. 2018, 19(9), 2712; https://doi.org/10.3390/ijms19092712 - 11 Sep 2018

Cited by 1 | Viewed by 2839

Abstract

Extract of the Blood Circulation-Promoting Recipe (EBR-84) from the Chinese Herbal medicine “Blood Circulation Promoting Recipe” could retard retinopathy development. This study investigated whether EBR-84 protects retinas by inhibiting the β-catenin pathway using a rat model of retinopathy and a retinal ganglion cell 5 (RGC-5) cell death model. RGC death was induced by either N-methyl-d-aspartic acid (NMDA) or TWS119 (an activator of the β-catenin pathway). After the corresponding treatment with EBR-84, RGC death and the protein expression levels of β-catenin, cyclooxygenase-2 (COX-2), and vascular endothelial growth factor (VEGF) in rat retinas were examined. β-Catenin accumulated in the retinal ganglion cell layer (GCL) of NMDA-treated rats. EBR-84 (3.9, 7.8, and 15.6 g/kg) significantly attenuated the NMDA-induced RGC loss accompanying the reduction of β-catenin expression. Moreover, the expression levels of COX-2 and VEGF were decreased by EBR-84 in a dose-dependent manner. For the TWS119-treated rats, EBR-84 also ameliorated RGC loss and lowered the expression levels of β-catenin, COX-2, and VEGF. In vitro, EBR-84 increased the viability of NMDA-treated RGC-5 while decreased β-catenin expression. In conclusion, EBR-84 retarded ratretinopathy, and the β-catenin signaling pathway played an important role during this protective process. Full article

(This article belongs to the Special Issue Nanomedicine/Molecular Medicine)

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17 pages, 1943 KiB

Open AccessArticle

Suppression of Schistosoma japonicum Acetylcholinesterase Affects Parasite Growth and Development

by Hong You, Chang Liu, Xiaofeng Du, Sujeevi Nawaratna, Vanessa Rivera, Marina Harvie, Malcolm Jones and Donald P. McManus

Int. J. Mol. Sci. 2018, 19(8), 2426; https://doi.org/10.3390/ijms19082426 - 16 Aug 2018

Cited by 17 | Viewed by 3456

Abstract

To further investigate the importance of Schistosoma japonicum acetylcholinesterase (SjAChE) in cholinergic signaling for parasite growth and development, we used RNA interference (RNAi) to knock-down its expression in adults and eggs in vitro. This resulted in its reduced transcription but also expression of other important genes involved both in cholinergic signaling and glucose uptake were impacted substantially. Significant decreases in AChE protein expression, AChE enzymatic activity, and glucose uptake were observed in the SjAChE-knockdown parasites compared with luciferase controls. In vaccine/challenge experiments, we found that immunization of mice with recombinant SjAChE (rSjAChE) expressed in Escherichia coli elicited reductions in male worm numbers (33%), liver granuloma density (41%), and reduced numbers of mature intestinal eggs (73%) in the vaccinated group compared with the control group. These results indicate AChE plays an important role in the metabolism of male worms, and impacts indirectly on female fecundity leading to increased numbers of immature eggs being released and reduced sizes of liver granulomas. Furthermore, cytokine analysis showed that immunization of mice with rSjAChE elicited a predominantly Th1-type immune response characterized by increased production of IFNγ in splenic CD4⁺ T cells of vaccinated mice. The study confirms the potential of SjAChE as a vaccine/drug candidate against zoonotic schistosomiasis japonica. Full article

(This article belongs to the Special Issue Nanomedicine/Molecular Medicine)

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18 pages, 3450 KiB

Open AccessArticle

Photothermally Triggered Endosomal Escape and Its Influence on Transfection Efficiency of Gold-Functionalized JetPEI/pDNA Nanoparticles

by Lotte M. P. Vermeulen, Juan C. Fraire, Laurens Raes, Ellen De Meester, Sarah De Keulenaer, Filip Van Nieuwerburgh, Stefaan De Smedt, Katrien Remaut and Kevin Braeckmans

Int. J. Mol. Sci. 2018, 19(8), 2400; https://doi.org/10.3390/ijms19082400 - 14 Aug 2018

Cited by 17 | Viewed by 4594

Abstract

Plasmonic nanoparticles for drug delivery have attracted increasing interest over the last few years. Their localized surface plasmon resonance causes photothermal effects on laser irradiation, which allows for delivering drugs in a spatio-temporally controlled manner. Here, we explore the use of gold nanoparticles (AuNP) as carriers for pDNA in combination with pulsed laser irradiation to induce endosomal escape, which is currently considered to be one of the major bottlenecks in macromolecular drug delivery on the intracellular level. In particular, we evaluate nanocomplexes composed of JetPEI (polyethylenimine)pDNA and 10 nm AuNP, which do not exhibit endosomal escape by themselves. After incubating HeLa cells with these complexes, we evaluated endosomal escape and transfection efficiency using low- and high-energy laser pulses. At low laser energy heat is produced by the nanocomplexes, while, at higher laser energy, explosive vapour nanobubbles (VNB) are formed. We investigated the ability of heat transfer and VNB formation to induce endosomal escape and we examine the integrity of pDNA cargo after inducing both photothermal effects. We conclude that JetPEI/pDNA/AuNP complexes are unable to induce meaningful transfection efficiencies because laser treatment causes either dysfunctionality of the cargo when VNB are formed or forms too small pores in the endosomal membrane to allow pDNA to escape in case of heating. We conclude that laser-induced VNB is the most suitable to induce effective pDNA endosomal escape, but a different nanocomplex structure will be required to keep the pDNA intact. Full article

(This article belongs to the Special Issue Nanomedicine/Molecular Medicine)

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12 pages, 2943 KiB

Open AccessArticle

Miniaturized Biomedical Sensors for Enumeration of Extracellular Vesicles

by Anil Kumar Pulikkathodi, Indu Sarangadharan, Chiao-Yun Lo, Po-Hsuan Chen, Chih-Chen Chen and Yu-Lin Wang

Int. J. Mol. Sci. 2018, 19(8), 2213; https://doi.org/10.3390/ijms19082213 - 29 Jul 2018

Cited by 13 | Viewed by 3247

Abstract

In this research, we have realized a rapid extracellular vesicle (EV) quantification methodology using a high field modulated AlGaN/GaN high electron mobility (HEMT) biosensor. The unique sensing structure facilitated the detection of the sub-cellular components in physiological salt environment without requiring extensive sample pre-treatments. The high field operation of GaN HEMT biosensor provides high sensitivity and wide dynamic range of detection of EVs (10⁷–10¹⁰ EVs/mL). An antibody specific to the known surface marker on the EV was used to capture them for quantification using an HEMT biosensor. Fluorescence microscopy images confirm the successful capture of EVs from the test solution. The present method can detect EVs in high ionic strength solution, with a short sample incubation period of 5 min, and does not require labels or additional reagents or wash/block steps. This methodology has the potential to be used in clinical applications for rapid EV quantification from blood or serum for the development of diagnostic and prognostic tools. Full article

(This article belongs to the Special Issue Nanomedicine/Molecular Medicine)

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21 pages, 3161 KiB

Open AccessArticle

Multifunctional Tannic Acid/Silver Nanoparticle-Based Mucoadhesive Hydrogel for Improved Local Treatment of HSV Infection: In Vitro and In Vivo Studies

by Emilia Szymańska, Piotr Orłowski, Katarzyna Winnicka, Emilia Tomaszewska, Piotr Bąska, Grzegorz Celichowski, Jarosław Grobelny, Anna Basa and Małgorzata Krzyżowska

Int. J. Mol. Sci. 2018, 19(2), 387; https://doi.org/10.3390/ijms19020387 - 28 Jan 2018

Cited by 65 | Viewed by 6720

Abstract

Mucoadhesive gelling systems with tannic acid modified silver nanoparticles were developed for effective treatment of herpes virus infections. To increase nanoparticle residence time after local application, semi solid formulations designed from generally regarded as safe (GRAS) excipients were investigated for their rheological and mechanical properties followed with ex vivo mucoadhesive behavior to the porcine vaginal mucosa. Particular effort was made to evaluate the activity of nanoparticle-based hydrogels toward herpes simplex virus (HSV) type 1 and 2 infection in vitro in immortal human keratinocyte cell line and in vivo using murine model of HSV-2 genital infection. The effect of infectivity was determined by real time quantitative polymerase chain reaction, plaque assay, inactivation, attachment, penetration and cell-to-cell assessments. All analyzed nanoparticle-based hydrogels exhibited pseudoplastic and thixotropic properties. Viscosity and mechanical measurements of hydrogels were found to correlate with the mucoadhesive properties. The results confirmed the ability of nanoparticle-based hydrogels to affect viral attachment, impede penetration and cell-to-cell transmission, although profound differences in the activity evoked by tested preparations toward HSV-1 and HSV-2 were noted. In addition, these findings demonstrated the in vivo potential of tannic acid modified silver nanoparticle-based hydrogels for vaginal treatment of HSV-2 genital infection. Full article

(This article belongs to the Special Issue Nanomedicine/Molecular Medicine)

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Review

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20 pages, 2531 KiB

Open AccessReview

Ocular Drug Delivery: Role of Degradable Polymeric Nanocarriers for Ophthalmic Application

by Cheng-Han Tsai, Peng-Yuan Wang, I-Chan Lin, Hu Huang, Guei-Sheung Liu and Ching-Li Tseng

Int. J. Mol. Sci. 2018, 19(9), 2830; https://doi.org/10.3390/ijms19092830 - 19 Sep 2018

Cited by 160 | Viewed by 17237

Abstract

Ocular drug delivery has been a major challenge for clinical pharmacologists and biomaterial scientists due to intricate and unique anatomical and physiological barriers in the eye. The critical requirement varies from anterior and posterior ocular segments from a drug delivery perspective. Recently, many new drugs with special formulations have been introduced for targeted delivery with modified methods and routes of drug administration to improve drug delivery efficacy. Current developments in nanoformulations of drug carrier systems have become a promising attribute to enhance drug retention/permeation and prolong drug release in ocular tissue. Biodegradable polymers have been explored as the base polymers to prepare nanocarriers for encasing existing drugs to enhance the therapeutic effect with better tissue adherence, prolonged drug action, improved bioavailability, decreased toxicity, and targeted delivery in eye. In this review, we summarized recent studies on sustained ocular drug/gene delivery and emphasized on the nanocarriers made by biodegradable polymers such as liposome, poly lactic-co-glycolic acid (PLGA), chitosan, and gelatin. Moreover, we discussed the bio-distribution of these nanocarriers in the ocular tissue and their therapeutic applications in various ocular diseases. Full article

(This article belongs to the Special Issue Nanomedicine/Molecular Medicine)

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38 pages, 2486 KiB

Open AccessReview

Microfluidic and Paper-Based Devices for Disease Detection and Diagnostic Research

by Joshua M. Campbell, Joseph B. Balhoff, Grant M. Landwehr, Sharif M. Rahman, Manibarathi Vaithiyanathan and Adam T. Melvin

Int. J. Mol. Sci. 2018, 19(9), 2731; https://doi.org/10.3390/ijms19092731 - 12 Sep 2018

Cited by 45 | Viewed by 10356

Abstract

Recent developments in microfluidic devices, nanoparticle chemistry, fluorescent microscopy, and biochemical techniques such as genetic identification and antibody capture have provided easier and more sensitive platforms for detecting and diagnosing diseases as well as providing new fundamental insight into disease progression. These advancements have led to the development of new technology and assays capable of easy and early detection of pathogenicity as well as the enhancement of the drug discovery and development pipeline. While some studies have focused on treatment, many of these technologies have found initial success in laboratories as a precursor for clinical applications. This review highlights the current and future progress of microfluidic techniques geared toward the timely and inexpensive diagnosis of disease including technologies aimed at high-throughput single cell analysis for drug development. It also summarizes novel microfluidic approaches to characterize fundamental cellular behavior and heterogeneity. Full article

(This article belongs to the Special Issue Nanomedicine/Molecular Medicine)

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