16^th World Medical Nanotechnology Congress September 3-4, 2018 Tokyo, Japan

Monika Dvořáková has her expertise in evaluation of oxidative stress in different free radical diseases. Recently, her attention has been devoted to studying the potential risk of metal and metaloxide nanoparticles used for biomedical application with focus on the NP influence on the oxidative status.

In recent years, the interest in nanotechnology in medicine involves mainly prevention, diagnostics and treatment of human diseases such as cancer. Nanoparticles (NPs) are able to target the drug delivery into the exact place of the body, to protect drugs from degradation in gastrointestinal tract, as well as to carry slightly water soluble drugs. Despite the increasing popularity of nanomedicine, application of NPs has been limited due to their potential toxicity. It is known they can induce production of reactive oxygen species, leading to an oxidative stress. Our goal was to evaluate the effect of the polymeric NP, poly(ethylene glycol)−block−poly(lactic acid) (PEG−b−PLA) on the activity of selected antioxidant enzymes of the organism in two different life stages. Female Wistar rats were neonatally administered intraperitoneally with PEG−b−PLA NPs [20 mg/kg of b.w. (PEG20) or 40 (PEG40) mg/kg of b.w.] from postnatal day 4 (PND4) to PND7. We determined activities of catalase, glutathione peroxidase (GPx) and superoxide dismutase (SOD) in hemolysates of infantile (sacrificed on PND17) and adult (sacrificed after PND176) female rats. In adult vehicle-treated animals (controls), a significant decrease in catalase activity was observed, but, on the other hand, a significant increase in GPx and SOD activity compared to infantile controls was confirmed. In the hemolysates of infantile rats, both doses of PEG−b−PLA NPs after neonatal administration increased catalase, Gpx as well as SOD activities compared to controls. Surprisingly, in adult rats, the activities of Gpx and SOD decreased significantly after neonatal administration of both doses of PEG−b−PLA NPs.Obtained data indicate a possible age-related association between the activities of antioxidant enzymes and neonatal PEG−b−PLA NPs administration in female rats. Therefore, further investigation is necessary to clarify the mechanism of NPs effect and to evaluate their impact on the organism.

Zhifu Yin has completed his PhD at the age of 30 years from Dalian University of Technology. He is a lecture in Jilin University from July 2016. He has published more than 30 papers in reputed journals and has been serving as an reviewer for more than 5 reputed journals.

All polymer-based nanofluidic chips are becoming increasingly important for biological and medical applications. Future advances in nanofluidics and its utilization in commercial applications depend on the development and fabrication of low cost and high fidelity nanofluidic chips. It is easy to improve replication precision of nano-trenches by means of increasing imprinting temperature, pressure and duration. However, without the support of nano-mold, the replicated nanochannels are apt to block after bonding process. The fabrication of high fidelity nanofluidic chips depends on bonding process rather than imprinting process. This work presents a novel bonding method for nanochannels based on PDMS spincoating. With optimized parameters, the size of the nanochannels can be decreased by 67 % after PDMS spincoating. Experimental results show that 60 nm (both for width and depth) nanochannels with high uniformity can be fabricated without any block.

Born in Havana, Cuba in 1962, graduated in Physics in 1985, working for the Microelectronics Industry, as head of final control investigations degradation production of electronic components, working for the Electronics Industry, department of reliability, characterization work performed Luma-Chroma plate worker Research Institute of Metrology, work Challenges of Metrology in Cuba in the era of nanotechnology. Work published in the ISO TC 229, ISO TC229 / IEC 113, required for conformity assessment of research and nano-scale productions Tool page. Master of Science.

The convergence of nanotechnologies generates synergies among different technologies to say, nanotechnologies, neurotechnology, computers and biotechnology, these technologies must converge( 7) itheir regulations, the application of medical devices in nanotechnologies should lead us to a link between the technical committee TC 210 and ISO technical committee 229 link that does not exist in our work in this moment In this do an analysis of the management of risk from an optical NC-ISO 14971(1). Studying the global trend in this respect as imported for manufacturers medical Devices worldwide. The convergences of technologies is a consequence of atomic precision, where the boundary between the biotic and abiotic mute blur the interaction. The interaction between nanotechnologies, biotechnology and informatics and communications (NBI) generates a synergy of unusual consequences of all is known that the industry of semiconductor( 5)s is the one of greater precision that is atomic, the new medical devices that will be applied in the teranocis will dose Physical principles that will be governed under the laws of quantum mechanics( 4), but there are two problems that have not been solved even though they are one the non-existence of quantum biology and the transition from quantum to classical mechanics. On the other hand, the redefinition of the international system of units based on the universal constants that will be implemented by 2018 has a deficiency that is the second that redefirms implies redefinition of the meter the chain of traceability proposed for nanometrology presents a serious difficulty when putting the microcopy of atomic force wing of effect tunnel situation that is changing the verification of the Wiedemann-Franz law (8) at atomic level yields a result where the phononic component is taken into account, a result that launches STM to the cusp of the chain of traceability above inclusive of interferometry

Dr. V. Rama Mohan Gupta has his expertise in the development of “Spherical agglomerates, Co-crystals, Proniosomes, Microspheres and different types Nanocarriers systems to target different organs. He has worked on many solubility enhancement techniques, formulation development and in vitro-in vivo characterization studies for various drugs during his Ph.D. research work. Presently he has guiding many research scholars who are working on Chronotherapeutics, Targeted and various controlled release drug delivery systems. Apart from this he is serving as Principal and HOD of Pharmacy colleges from past 15 years. He is serving as president-elect of India-Telangana ISPOR Regional chapter, involved in disseminating the knowledge of Pharmacoeconomics, drug use and patient centered outcomes. He has published nearly 84 research publications in various national and international journals.

The purpose of present work was to formulate fluconazole loaded microsponge-based topical delivery system for modified release. Microsponges with varied drug-polymer ratios were prepared by emulsion solvent diffusion technique using ethyl cellulose as release retard material. Prepared microsponges were studied for particle size and physical characterization. Scanning Electron Microscopy (SEM) images showed the microsponges porous and spherical in shape. The microsponges were then incorporated in carbopol gel and evaluated for pH, viscosity, spreadability, drug content, in vitro release. The In vitro drug release showed that microsponges with 1:1.5 drug-polymer ratios (F3) were more efficient to give sustained release of 74.2% at the end of 8 hrs. All the microsponge gel formulations (i.e.F1-F10) showed better results like pH between 6.5-7.0, viscosity between 25,030-47,390 cps, spreadability 2-4cm/s and drug content of 76.20±0.02% to 96.41±0.01%. Hence, the fabricated microsponge based formulation of fluconazole would be anticipation and promising substitute to conventional therapy of skin infections.

JM López-Romero is professor of Organic Chemistry at the University of Málaga (Spain). Postdoctoral studies were carried out at the University Pierre et Marie Curie (Dr. Max Malacria, Paris VI, France) and University of Houston (Dr. Chengzhi Cai, USA). He is founder and director of Icon Nanotech S.L., a Spanish Spin-Off company dedicated to nanotechnology and natural products. He has published more than 60 papers in reputed journals. Research interest includes synthesis of natural products, macromolecules and nanoparticles, all of them with applications in nanomedicine, cosmetics and in surface nanostructuration

Paclitaxel (PTX), one of the most effective drugs for the treatment of breast and lung cancer, is limited by its severe side effects and low tumor selectivity. We carried out pH responsive hollow-poly(4-vinylpyridine) (hollow-p4VP) and Au (Au@p4VP) nanoparticles (NPs) that have been used to generate PTX@p4VP NPs, employing a technique in which a gold core in the center of the NP is further oxidized to produce the hollow structure into which PTX molecules can be incorporated. The hollow-p4VP NPs exhibit good physicochemical properties and displayed excellent biocompatibility when tested on blood (no hemolysis) and cell cultures (no cytotoxicity). Moreover, mean diameter, ranging from 150 to 57 nm, can be accurately controlled upon varying the monomer concentration at synthesis. Interestingly, PTX@p4VP NPs significantly increased PTX cytotoxicity in human lung (A-549) and breast (MCF-7) cancer cells with a significant reduction of PTX IC50 (from5.9 to 3.6 nM in A-549 and from 13.75 to 4.71 nM in MCF-7). In addition, PTX@p4VP caused a decrease in volume of A-549 and MCF-7 multicellular tumor spheroids (MTS), an in vitro system that mimics in vivo tumors, in comparison to free PTX. This increased antitumoral activity is accompanied by efficient cell internalization and increased apoptosis, especially in lung cancer MTS. Our results offer the first evidence that hollow-p4VP NPs can improve the antitumoral activity of PTX. This system can be used as a new nanoplatform to overcome the limitations of current breast and lung cancer treatments. The good results obtained for PTX allowed us to extend the use the colloidal hybrid system to doxorubicin (Dox) and 5-fluorouracil (5Fu). Here we present a complete characterization of PTX@p4VP NPs together with our preliminary results for these two anticancer drugs included into hollow polymeric systems.

Fatemeh Gheybi is currently Assistant Professor at Mashhad University of Medical Sciences in Iran. She obtained her M.S. degrees in Nutrition and Biochemistry and her Ph.D. in Medical Nanotechnology at Tehran University of Medical Science. Fatemeh has her expertise in liposomal drug delivery systems and targeted cancer therapy. In her Ph.D. thesis work under supervision of professor Mahmoud R. Jaafari, she studied pH sensitive nanoliposomal formulation of a polyphenolic compound, Silybin. Her work lead to development of a new method for incorporation of polyphenols into the liposomes. Fatemeh has over 10 publications and 3 patents in the field of liposome technology.

According to different studies, high intake of natural products is associated with reduced cancer risk. It is suggested that the specific concentrations of phytochemicals may have cancer chemopreventive effects without causing significant levels of toxicity. Nowadays, there is an increasing emphasis on combination chemotherapy using cytotoxic and natural chemotherapeutic agents. The successes of combination chemotherapy suggested that all cancers could be treated by providing the correct combination of drugs at the correct doses and correct intervals of administration. Silybin is the active ingredient of Silybum Marianum that has been used in traditional medicine because of its liver protective effects in different countries. It can also modulate imbalance between cell survival and apoptosis through interference with expressions of cell cycle regulators and proteins involved in apoptosis. In present study, nanoliposomal formulations containing silybin, have been prepared and their anti-tumor activities alone and in combination with Doxil were assessed in a mouse TUBO breast tumor model. After injection of liposomes, tumor size and survival were monitored on 3 occasions a week for 100 days. The results of in vivo studies showed that anti-tumor efficacy of silybin liposome formulations alone in treated mice were not significantly more than control animals on day 27. In the other two groups, the efficacy of Doxil and Doxil-Silybin (p<0.001) liposomes were significantly more than control animals (Figure 1). Also according to our data, even 100 days after inoculation, 83% percent animal survival was observed in Doxil-silybin liposome were used simultaneously but in case of Doxil alone, the survival percentage reached to almost 40% and for silybin liposomes alone reached to 20%. Therefore there is a significant difference between survival percent in control group with Doxil alone (p<0.001) and Doxil-silybin liposomes combination (p<0.001). The survival percent of the control group reached to zero, on around 40 days after tumor inoculation

Victoria Uvarova is a PhD student of the Chemical Enzymology Department of Lomonosov Moscow State University. Currently she has 8 reports at conferences, 5 awards, 2 patents in press, 2 internships in large Russian laboratories specializing in biotechnology and nanomaterials. She participated in the project for new systems of delivery of nucleic acids by magnetic nanoparticles with a lipid coating in Laboratory "Biomedical Nanomaterials" (NUST MISiS).

Small interfering RNA (siRNA) is a promising technology based on mRNA transcripts gene degradation for decreasing of protein synthesis level, for example apolipoprotein B, produced in liver, which correlates with several cardiovascular diseases. One of perspective approach is to facilitate siRNA uptake during the endocytosis is encapsulation within non-viral nanoparticles such as superparamagnetic iron oxide nanoparticles (SPIONs). SPION, due to their magnetic properties that provides targeted delivery into the cytoplasm and might increase transfection efficiency by applying an alternating magnetic field (magnetofection). Lipid-coated (C12-200, DSPE, cholesterol and different modifications of PEG lipids) SPION with loaded siRNA ApoB were investigated for cell uptake. It was shown that SPION internalize into cells (HepG2, Huh7) after 20-30 minutes of incubation by clathrin-mediated endocytosis. Biological distribution of various types of SPION (cubes, spheres) in vivo shows significant level of accumulation in the liver which was observed already 1 h after the injection, and maintained for 48 h (MRI). Localization of nanoparticles was shown by histological staining in the liver ex vivo. Cubic nanoparticles with iron oxide core in range of 10 to 20 nm and hydrodynamic size less than 100 nm reach higher levels of accumulation in hepatocytes (more than 90 %), whereas larger particles were absorbed by Kupffer cells. Accordingly, lipid-coated nanoparticles show promising potential as a platform for siRNA delivery to the liver.The work was supported by the Ministry of Education and Science of the Russian Federation (grant no. 14.578.21.0201 (RFMEFI57816X0201)).

Michael Erkelenz studied Biology (B. Sc.) at Heinrich-Heine-University Düsseldorf, specialized in Medical Biology (M. Sc) at University Duisburg-Essen and is PhD student in Physical Chemistry with Prof. Sebastian Schlücker and a member of the graduate school of the Collaborative Research Center 1093 founded by the German Research Foundation (DFG).

Supramolecular ligands like guanidiniocarbonylpyrrole (GCP) and the molecular tweezer CLR01 are small molecules for protein recognition, in contrast to the commonly used large antibodies. This is mainly based on their ability to bind proteins via non-covalent interactions at accessible residues of the protein surface which can be localised, for example, by X-ray crystallography or molecular dynamics simulations.1 The design of a modular platform with many precisely positioned low-affinity protein-binding supramolecular ligands and an overall high avidity could be the next step for protein recognition in biomedical applications.2 The molecular recognition of proteins with GCP is based on the residue specific binding of carboxylates while the Janus-type tweezer binds with its aromatic cavity the apolar chain of lysin and arginine and the side chain cation with the hydrogen phosphate anion.3,4 The combination with a programmable DNA origami platform enables the binding of proteins in their native states via nanopositioned supramolecular ligands resulting in high avidity. The controlled deposition of the ligands on the DNA origami is achieved by hybridising complementary ssDNA strands: one stands out of the DNA origami and another free ssDNA strand, which is linked optionally to an ExoS-peptide or a supramolecular ligand. As a gold standard for binding 14-3-3 with high affinity, a short peptide derived of the binding motif of the ExoS enzyme (Pseudomonas aeruginosa) is used.

Francisca Villanueva-Flores is studying her last year of PhD in biochemistry at Instituto de Biotecnología in the Universidad Nacional Autónoma de México. Her main research focuses in the development of medical nanodevices for neuronal tissue engineering. In her PhD, she synthetized a nanoimplant for restoring cellular function (unpublished data). Her research interests also include the understanding of cell-nanomaterial interactions to develop novel, efficient and safe therapeutic nanobiomaterials.

The development of novel materials as scaffolds for cell culture has gained attention. The current challenge is to provide a scaffold that mimics natural tissues. We synthetized at physiological temperature a pH-responsive and biocompatible nanostructured hydrogel with three different crosslinking degrees by varying the content of glutaraldehyde (GA). According with our data of scanning electron microscopy (SEM) and FTIR, we observed that the hydrogel is conformed highly ordered nanofibers of poly (vinyl alcohol co-vinyl acetate) (nsPAcVA). By atomic force microscopy (AFM), we showed that nsPAcVA has nanopores homogeneously distributed on its surface. We characterized the relative amount of remaining hydroxyl groups and of formed acetal bridges by FTIR, and by mechanical tests, we measured the Young’s modulus, strain stress, elastic deformation and tensile strength. nsPAcVA had swelling dynamics dependent on pH and crosslinking. By cyclic voltammetry, we showed that nsPAcVA has ionic conductivity properties inversely proportional to its crosslinking degree. Based on this, we evaluated its capability to controllably release a model molecule. Diffusion analysis through the Peppas equation showed that at lower crosslinking degrees (5 and 10% of GA content), diffusion from nsPAcVA was Fickian. Moreover, we demonstrated for the very first time that nsPAcVA is an efficient scaffold for growth of mammalian cells (embryonic mouse hypothalamic mHypoE-N1 and human lung carcinoma A-549 cells). mHypoE- grown on nsPAcVA had lower proliferation than the control, but after 108 h of adaptation, cells proliferated at comparable growth levels than the control. No significant difference in A-549 cell growth over nsPAcVA and the control was observed. We present a very easy synthesizable, cheap, biocompatible and nanostructured scaffold for controlled drug release with promising physicochemical characteristics to be applied as a tissue engineering material that integrates abiotic and biotic components towards a new generation of smart implants which ultimately could mimic natural tissues.

Steven Mufamadi is the founder of Nabio Consulting (Pty) Ltd, a start-up company on nanotechnology and biotechnology that is based in South Africa (SA). His expertise is on bio-nanotechnology and nanomedicine formulations for pharmaceutical application. Mufamadi he is also co-founder of the nanotechnology symposia series on HIV/AIDS, TB, malaria, cancer, energy and water in partnership with SA government, an initiative that is aiming on facilitation of nanotechnology development, innovation, commercialization and public engagement in SA through dialogues between government/policy makers, researchers, industry, entrepreneurs and investors.

Cancer is a global threat; about 8.2 million people die as a result of cancer each year. In South Africa, cancer has increased from 5.6 to 9% between 2006 and 2015. Nanotechnology is a most promising field for generating new applications in medicine. The anti-proliferative and apoptosis inducing properties of silver nanoparticles (Ag NPs) makes them ideal candidates for anticancer therapy. The purpose of this study is to illustrate the biological synthesis of Ag NPs using plant extracts for Nanomedicine; also, to showcase the mechanism of action of the Ag NPs on cancer cell lines and the potential impact in oncology. Green synthesis of Ag NPs is a simple synthetic technique which could be achieved by blending of silver ions together with plant extracts, which can act as reducing and capping agents, to form Ag NPs with different sizes and shapes. This approach offers simplicity, rapid synthesis, environment friendly, inexpensive biological procedure for nanoparticle fabrication with low systemic toxicity to human. Additionally, green synthesis approach using plant extracts are easy to scale up for larger-scale production of nanoparticles. The use of Ag NPs as a new generation of anticancer therapy showed improved in vitro anti-cancer efficacy against different cancer cell lines at low concentration. The main mechanism of action of Ag NPs on cancer cell death involves the uptake of Ag NPs inside the cell via endocytosis or diffusion, which causes mitochondrial dysfunction and formation of reactive oxygen species (ROS), resulting in damage to cellular components such as proteins, DNA and cell membrane (Figure 1). Many studies showed that cell uptake and anticancer activity to be influenced by nanoparticle’s size (1-100nm). The toxicity of green synthesized Ag NPs on normal cells highly depends on the plant extract used for the stabilization and reduction of metal ion. Conclusion & Significance:Green silver nanotechnology using plant extracts promising to offer anticancer therapy at atomic scale and molecular level. However, in-depth study on Ag NPs properties in mammalian immune system and in vivo toxicity study is recommended in order to confirm safety and clinical significance.

Hao Liang is a PhD student of Beijing University of Technology and majoring in bioengineering from College of Life Science and Bioengineering. He has specialized in developing novel vaccines and immune therapy and has participated in a national natural science project, design and construction of beta-glucan/CpG ODN-based dual combined nano-adjuvant and studies on its immune effects of Enterovirus 71 vaccine (Grant No. 31770999)

Enterovirus 71 (EV71) is a major causative pathogen of Hand, Foot and Mouth Disease (HFMD) in young children. HFMD induced by EV71 can cause a high rate of neurologic complications and even death. Although there are three inactivated EV71 vaccines were approved in China, the adjuvants used with EV71 vaccines have many defects and need to be improved. In this study, we generated a novel protamine/carboxymethyl dextran based nano-adjuvant for CpG Oligonucleotides (ODNs) and EV71 inactivated vaccine co-delivery. The new nano-vaccine was administrated in mice to evaluate its immune activity. Results showed that it can induce high level EV71-specific neutralizing antibodies toward Th1-bias response. The specific antibodies from mice administered nano-vaccine showed stronger neutralization activity in vitro and in vivo than any other groups with nano-adjuvant or CpG ODNs alone. The CpG-1826，a B-type CPG ODNs were loaded in the nano-adjuvant and stimulated immune cells to secrete a great deal of both IFN-α and IFN-γ in vivo. This result demonstrated that nano-adjuvant endows CpG-1826 with A-type CpG ability to secreting type I IFN without losing its B-type activity to enhance immune response. Taken together, the novel nano-vaccine can be a potential candidate for medically necessary EV71 vaccines, and CpG ODNs loaded nano-adjuvant may be an excellent adjuvant used in other immunotherapeutic applications which demand type I and type II IFN induction.