Scientific Program

Day 1 :

Biography:

Ziyad S. Haidar is a Full Professor of Biomaterials and Tissue Engineering and the Scientific Director of the Faculty of Dentistry, Universidad de los Andes in Santiago de Chile. Concurrently, he is the Founder and Head of the Biomaterials, Pharmaceutical Delivery and Cranio-Maxillo-Facial Tissue Engineering Laboratory/Research Group (BioMAT'X Chile; please visit: http://www.uandes.cl/facultad-de medicina/biomaterials-pharmaceutical.html). Haidar also serves as the Head of Innovation at the Centro de Investigación e Innovación Biomédica and a Faculty member in the Doctoral Program (BioMedicine) at the Facultad de Medicina. He is a Visiting Professor at several institutions, such as the Division of MaxilloFacial Surgery at the Universidad de la Frontera in Temuco. Haidar is a trained dentist, implantologist and an oral and maxillofacial surgeon with a PhD in nanobiomaterials, pharmaceuticals and tissue engineering from McGill University, Montréal, Canada. He is an international speaker with more than 125 publications, conference proceedings, text-books and patents and is an editorial board member of several national and international peer-reviewed scientific journals / periodicals. 

Abstract:

Statement of the Problem: Saliva plays a major role in maintaining oral health. This becomes more apparent when the amount and quality of saliva are reduced, often due to medications, Sjögren’s syndrome and especially ionizing radiation therapy for tumors of the head and neck, during which the salivary glands are included within the radiation zone. While temporarily alleviated via “intensive” regimens of palliative home and professional care, many Head and Neck Cancer patients are unable to maintain the diligence required to be effective. More considerably, those affected by irreversible salivary gland dysfunction (and/or using amifostine, I.V.) often choose to terminate their radiotherapy course pre-maturely as they become severely malnourished and experience a significant deterioration in their QoL, mainly owing to hyposalivation.

Aims: Evaluate the radioprotective effect of core-shell nanocapsules designed for sequential/timely protein(s) release, following a single local injection into murine submandibular salivary glands pre-irradiation.

Materials and Methods: Loaded core-shell nanocapsules with the protein(s) were directly administered into the salivary glands of the experimental group 24 hours before radiation and PBS was injected into the glands, likewise, for the controls. Salivary flow rates and salivary protein excretion/content were evaluated using ELISA over a 3mons. period post-treatment. Histological evaluation of structures and analysis of apoptosis/proliferation were performed. Timely bio-distribution assays followed.

Findings: Experimental animals demonstrated increased salivary flow rates compared to controls. Protein content was comparable to that of pre-radiation level. Histological evaluation revealed acinar cells with less vacuoles and nuclear aberrance in experimental group compared to controls and the amount of mucin stained by alcian blue was larger, in the latter. Protein therapy resulted in less apoptotic activities detected by TUNEL assay and similar proliferative indices as in controls.

Conclusion & Significance: Biocompatible, stable, reproducible and customizable core-shell nanoparticulate layer-by-layer self-assembled delivery system is presented. Our findings suggest that the local sequential release of a protein cocktail (in specific dosage and order) into murine salivary gland highly prevents radiation-induced damage via reducing apoptosis. This approach also promotes the in situ proliferation of salivary gland cells.

Keynote Forum

Alain L. Fymat

International Institute of Medicine & Science, USA

Keynote: Nanotechnology may provide new hope for brain cancer therapy

Time : 10:40-11:20

Biography:

Abstract:

Cancer cells are notoriously resistant to drugs intended to kill them by rerouting the signaling networks responsible for cancer cells' growth, proliferation, and survival. A drug may block a particular signaling pathway but within a matter of days (minutes in some cases), cancer cells begin to rely on alternate pathways to promote their survival. The simultaneous use of several drugs (“rational combination therapy”)  is meant to attack both the primary and alternate pathways to preemptively block the cancer cells' escape route. Unfortunately, the efficacy of many combination therapies has been limited because drugs have very different chemical properties, which cause them to travel to different parts of the body and enter cancer cells at different rates. The situation is considerably more complicated for brain cancer (glioblastoma multiform or octopus tumor) because the cancer cells extend their tendrils into the surrounding tissue, which is virtually inoperable, resistant to therapies, and always fatal. A major obstacle to treatment is the blood brain barrier or network of blood vessels that allows essential nutrients to enter the brain but block the passage of other substances. I will describe novel nanotechnology approaches for delivering drugs across and around the brain protective barriers.

 

Biography:

Henrique Faneca is principal investigator at Centre for Neuroscience and Cell Biology, and invited assistant professor at University of Coimbra. He received his Ph.D. degree in Biochemistry from Coimbra University in 2005. The main focus of his research is the development of lipid- and polymeric-based nanosystems for gene and drug delivery into target cells and the generation of new antitumor strategies, involving different gene therapy approaches either per se or in combination with chemotherapeutic agents. Henrique Faneca is author of more than 45 scientific papers corresponding to over 1500 citations and to an h-index of 19.

Abstract:

Cancer is one of the major causes of death, since conventional available treatments, in most of the cases, do not allow a cure of the disease. Despite the ongoing efforts, current treatment options are associated to multiple limitations, including reduced therapeutic efficacy and high side effects. The lack of effective and well-tolerated cancer treatments highlights the urgent need for the development of new therapeutic approaches, such as those involving the combination of gene therapy and chemotherapy. However, the synchronized application of these two types of strategies requires the development of efficient delivery nanosystems, in order to promote an effective and specific delivery of both therapeutic molecules into tumors, while avoiding their release in healthy tissues.  

In this context, we have recently developed new gene delivery nanosystems, polymer-based ones that have the ability to condense and efficiently deliver genetic material, and lipid-based ones that have the ability to specifically and efficiently deliver genetic material into HCC cells both in vitro and in vivo. Moreover, we have also shown that combination of antitumor gene therapy strategies, such as those including therapeutic genes or anti microRNA oligonucleotides, with low amounts of chemotherapeutic agents could result in a synergistic and significant antitumor effect.

Our present and future work will be focused on the engineering and characterization of novel nanoparticles, for drug and gene delivery, to mediate innovative multi-target antitumor strategies involving the combination of gene therapy and chemotherapy, in order to achieve a much higher antitumor efficacy and less side effects than conventional therapeutic strategies.

 

  • Nanomaterials and Nanoparticles | Nanomedicine in Cancer Therapeutics | Nanoparticle Based Drug Delivery

Session Introduction

Febee R. Y. Louka

UNIVERSITY OF LOUISIANA AT LAFAYETTE United States

Title: Nano- and Micro sensors in Determination of Cardiovascular System Lifespan

Time : 12:20-12:50

Speaker
Biography:

Dr. Louka holds a Ph.D. in Medicinal Analytical Chemistry (2004) from Ohio University, Athens OH. Currently, she is an associate professor in the Chemistry Department at the University of Louisiana at Lafayette. Her expertise is in environmental and medicinal analytical chemistry. She has accumulated over 25 years of teaching and research experience in instrumental analysis and has been certified by “Monitoring the environmental pollutants” by the [Marine Environmental Laboratories of the International Atomic Energy Agency in Monaco].

Dr. Louka started to focus on a new point of interest, by using biological backbone synthesized surfactants in drug delivery especially, for cancer cells and DNA cleavage. She is and will be investigating new inexpensive methods and eco-friendly adsorbents from Louisiana waste products and biological backbone synthesized surfactants.

Currently, Dr. Louka is the primary operator for all instruments in the analytical laboratories. She has extensive experience in the development of techniques and refinement of existing techniques of instrumental analysis. She was awarded the Outstanding Teaching Award College of Sciences 2016. She has published over 65 articles and presentations in peer-reviewed journals and conferences. She is a member of the American Chemical Society. She was one of four professors chosen from the whole university who established and initiate the Undergraduate Research Council. She has mentored more than 75 undergraduate students and two graduate students.

Nowadays, most of students under her supervision presented their results in the ACS meeting; others are co-authors in publications in highly ranked journals or professional meetings. A student in her undergraduate students’ research group was awarded the American Chemical Society Undergraduate Outstanding Analytical Chemist Award (2015). Dr. Louka was the awardee of Outstanding Undergraduate Research Mentoring 2014 and the Marvin and Warren Boudreaux / BoRSF Professorship in Chemistry 2012 – 2015 and 2015-2018. In 2016, She was the awarded Outstanding Teaching Award College of Sciences. She is also a member of the honors program which take the students to a level higher than regular students, preparing them for graduate, medical, pharmacy, and dental schools.

Abstract:

The imbalance between pro-oxidative and anti-oxidative processes increases with age. Dysfunctional endothelium is associated with impaired generation of nitric oxide (•NO) and overproduction of superoxide (O2•¯). This work describes the study of the relationship between the degree of endothelial dysfunction and the lifespan of the cardiovascular system. Ames dwarf, transgenic giant (Tg), hypertensive (SHR) and normal mice were used for these studies. The dwarf mice appear to outlive their normal siblings by an average of at least one year. However, the Tg mice have an over-expressed growth hormone that stimulates the growth of their bodies. One of the most important features of these mice is their reduced life expectancy.

An array of •NO, O2•¯ and peroxynitrite (ONOO¯) electrochemical nanosensors was used for the in vitro measurements. The balance between •NO, O2•¯ and ONOO¯ formations in Ames, giant and normal mice as well as SHR rats were investigated in their cardiovascular systems.

More favorable kinetics of •NO production with a concurrent quenched O2•¯ release was revealed in Ames compared to normal mice. The •NO/O2•¯ peak ratio was found to be 3.0 ± 0.29 times higher for Ames dwarf than their normal siblings. The case of transgenic mice was reversed, where the •NO/O2•¯ ratio was 2.8 ± 0.22 times less than that of controls from same Tg line. The ONOO¯ release was also determined in all species.

The rate of •NO production decreased from 1.2 + 0.1 μmol s-1 in WKY to 0.46 + 0.04 μmol s-1 in the SHR rats. Also, maximum •NO concentration in SHR was found to be much lower than that in WKY. On the other hand, the O2•¯ and ONOO¯ concentrations dramatically increased in SHR compared to WKY. Therefore, the change in dynamics of •NO release in the dysfunctional endothelium can be attributed to the increase in generation of O2•¯ as well as that of ONOO¯. Our data indicated that the reduced lifespan in Tg mice with dysfunctional endothelium is associated with high concentrations of O2•¯ and ONOO¯ that most likely leads to accumulation of tissue oxidative damage.

Danielyan Kristine

National Academy of Sciences of Armenia, Armenia

Title: Natural, Biological Based Nano Carriers Are Preferential For Drug Delivery

Time : 12:50-13:20

Speaker
Biography:

Dr Kristine  E. Danielyan graduated Yerevan State University, Department of Biochemistry (MS in Biochemistry) as well as obtained MS degree in Pharmacia. She defended her PhD thesis in 2003; partially part of the thesis work was performed based on the  DAAD fellowship in Marburg University, in Germany; the other part in H Buniatian Institute of Biochemistry of National Academy of Science of Armenia. Dr Danielyan performed her first PostDoc positions in Cerebral Vascular Disease Research Center, Department of Neurology, University of Miami School of Medicine with the further extension of the qualification in Institute for Environmental Medicine as well as Department of Pharmacology of the University of Pennsylvania, USA. Dr Danielyan was leading in Armenian, Russian, English lecture courses of Pharm chemistry, Pharmacognosy, Pharmacology more than 7 years in different Universities of Armenia. She has more than 30 publications, which are cited more than 250 times.

Abstract:

Introduction

Targeted drug delivery is one of the novel directions of the pharmacology. This direction includes numerous subtypes of drug delivery and one of them is the delivery of medical compounds by means of the biological based compounds or cells: erythrocytes, albumin nano particles, macrophages, antibodies against pathology initiated receptors, their targetable parts or antibodies against circulated in the organism natural carriers of the medicines, including predominantly albumins, globulins as well as red blood cells.

In our current experiments we examined the circulation time period of another compound – allopurinol, which is known as the inhibitor of Xanthine Oxidoreductase and passed several clinical trials as the antioxidant used for the treatment of ischemic stroke.

We proposed, allopurinol in experimental settings might serve as the compound, preventing the oxidative stress, whereas the albumin micro particles might preserve oncotic pressure and prevent Blood Brain Barrier (BBB) disruption.   

Methods

 Glutaraldehyde was used for the polymerization of albumin. Determination of the particle size was performed by the light as well as phase contrast microscopies and analyzed by Pixcavator 6.0 and Image Tool programs. Modification and establishment of iodine-based method served as the base for quantification of bound with the particles and free allopurinol. We have used intracranial peroxide injection as the reflection of oxidative stress part of the stroke pathology. Also, Evans Blue penetration was the indicating agent, evidencing about the extent of BBB disruption.

Results and discussions

There were compared the mortality rate, Evans Blue extravasation into the brain parenchyma, as well as the activity of Xanthine Oxidoreductase in 7 groups of the animals: injected with the large, middle, small size of the albumin micro particles coupled and not coupled with allopurinol and the group injected only with the allopurinol.

We concluded, the most prominent results are revealed after injection of small size micro particles coupled with allopurinol.

Key words: targeted drug delivery, albumin, erythrocytes, experimental stroke

 

Speaker
Biography:

Babak Negahdari has his expertise in medical biotechnology and nanotechnology. His experimental projects are based on application of nanotechnology and biotechnology in life improving of cancer patients and their therapeutic applications.

 

Abstract:

Angiogenesis is known as one of the hallmarks of cancer. Multiple lines evidence indicated that vascular endothelium growth factor (VEGF) is a key player in the progression of angiogenesis and exerts its functions via interaction with tyrosine kinase receptors (TKRs). These receptors could trigger a variety of cascades that lead to the supply of oxygen and nutrients to tumor cells and survival of these cells. With respect to pivotal role of angiogenesis in the tumor growth and survival, finding new therapeutic approaches via targeting angiogenesis could open a new horizon in cancer therapy. Among various types of therapeutic strategies, nanotechnology has emerged as new approach for the treatment of various cancers. Nanoparticles (NPs) could be used as effective tools for targeting a variety of therapeutic agents. According to in vitro and in vivo studies, NPs are efficient in depriving tumor cells from nutrients and oxygen by inhibiting angiogenesis. However, the utilization of NPs are associated with a variety of limitations. It seems that new approaches such as NPs conjugated with hydrogels could overcome to some limitations. In the present review, we summarize various mechanisms involved in angiogenesis, common anti-angiogenesis strategies, and application of NPs for targeting angiogenesis in various cancers.

 

Recent publications (minimum 5)

1. Nanoceria: a rare-earth nanoparticle as a novel anti-angiogenic therapeutic agent in ovarian cancer. PloS one 8(1):e54578

2. Gurunathan S, Lee K-J, Kalishwaralal K, Sheikpranbabu S, Vaidyanathan R, Eom SH. 2009. Antiangiogenic properties of silver nanoparticles. Biomaterials 30(31):6341-6350.

3. Jin H, Pi J, Yang F, Wu C, Cheng X, Bai H, Huang D, Jiang J, Cai J, Chen ZW. 2016. Ursolic acid-loaded chitosan nanoparticles induce potent anti-angiogenesis in tumor. Applied microbiology and biotechnology 100(15):6643-6652.

4. Hu H, You Y, He L, Chen T. 2015. The rational design of NAMI-A-loaded mesoporous silica nanoparticles as antiangiogenic nanosystems. Journal of Materials Chemistry B 3(30):6338- 6346.

5. Guarnieri D, Malvindi MA, Belli V, Pompa PP, Netti P. 2014. Effect of silica nanoparticles with variable size and surface functionalization on human endothelial cell viability and angiogenic activity. Journal of nanoparticle research 16(2):2229.

 

 

 

Speaker
Biography:

Ziyad S. Haidar is a Full Professor of Biomaterials and Tissue Engineering and the Scientific Director of the Faculty of Dentistry, Universidad de los Andes in Santiago de Chile. Concurrently, he is the Founder and Head of the Biomaterials, Pharmaceutical Delivery and Cranio-Maxillo-Facial Tissue Engineering Laboratory/Research Group (BioMAT'X Chile; please visit: http://www.uandes.cl/facultad-de- medicina/biomaterials-pharmaceutical.html). Haidar also serves as the Head of Innovation at the Centro de Investigación e Innovación Biomédica and a Faculty member in the Doctoral Program (BioMedicine) at the Facultad de Medicina. He is a Visiting Professor at several institutions, such as the Division of MaxilloFacial Surgery at the Universidad de la Frontera in Temuco. Haidar is a trained dentist,  implantologist and an oral and maxillofacial surgeon with a PhD in nanobiomaterials, pharmaceuticals and tissue engineering from McGill University, Montréal, Canada. He is an international speaker with more than 125 publications, conference proceedings, text-books and patents and is an editorial board member of several national and international peer-reviewed scientific journals / periodicals. 

Abstract:

Statement of the Problem: Paclitaxel (PAX) is a chemotherapy agent; effective in the treatment of a broad range of human malignancies. PAX has an anti-angiogenic activity through inhibiting vascular endothelial cell proliferation, motility and cord formation, at extremely low concentrations. Yet, side effects including hypersensitivity reactions, neurotoxicity, cardiotoxicity, and nephrotoxicity, are common, and are carrier-related/(CrEL). Multi-drug resistance (MDR) resulting in

chemotherapeutic failure has been reported. Cost is an issue as well. Hence, it is necessary to develop an alternative formulation fit for controlled PAX delivery. SLN (solid lipid nanoparticles) as potential anticancer drug delivery nanocarriers, exhibit a great superiority to modulate drug release, improve anti-cancer activity and overcome MDR. We developed a novel natural polymer-lipid hybrid formulation consisting of SLN as core and chitosan-hyaluronic acid (CH-HA) as a shell, with HA as the outmost layer; to enhance selectivity towards HA receptors in MCF-7 cells.

Aims: To investigate the potential of modified SLN for the delivery of PAX.

Materials and Methods: SLN loaded with PAX were prepared via high-pressure hot homogenization. Formulation parameters were optimized to obtain a high-quality delivery system. Selectivity towards HA receptors was tested in a breast cancer cell line.

Findings: Stable, reproducible and positively-charged nanoparticles

resulted. Findings reveal that CH-HA-coated SLN facilitated the targeting, cellular uptake and the time-/dose-controlled

delivery/release of PAX, enhancing intrinsic chemotherapeutic activities. CH exhibits an increased uptake efficiency by negatively-charged cancer cell membranes due to electrostatic interactions. HA is a bioadhesive compound capable of binding with high affinity to cell surface and intracellular receptors.

Conclusion & Significance: SLN are suitable carrier candidates for nanoncology given their localized, and potent cytotoxic potential overcoming MDR cancer cells. CD44, an HA receptor, is overexpressed in cancer stem cells, therefore, targeting CD44 using HA seems as a fine strategy to eliminate cells accountable for treatment failure and cancer recurrence

 

Muaathe A. Ibraheem

COLLEGE OF SCIENCE-UNIVERSITY OF DIAYLA, Iraq

Title: Study of Polypyrrole-coated electrospun polystyrene fibres by electrochemical oxidization

Time : 15:20-15:50

Speaker
Biography:

Abstract:

Polypyrrole (Ppy) was synthesized via a chemical oxidization method with FeCl3.6H2O (FCHH) on electrospun polystyrene fibres ESPSF. The spinning process was achieved by means of Electrospinning for three solutions of polystyrene PS including 3, 5 and 9 % wt/v of FCHH in dimethyl formamide (DMF). The fibres diameters were monitored  by scanning electron microscope SEM before and after coating and it was found that best results were achieved at low concentration of FCHH. Coating with Ppy has been performed in four exposure periods (90, 150, 200, 270 min) in a temperature was at 22C and the results show a direct relation between the mean diameter of fibres with quality of coating. The technique suggests a potential route towards the production of conducting fibre with micro/nanoscale dimensions  

Key words: Pyrrole, Electrospinning, polystyrene, conducting polymer & Fibres.

Speaker
Biography:

Abstract:

In this report, we present a facile approach to forming dendrimer-functionalized LAPONITE® (LAP) nanodisks loaded with gadolinium (Gd) for in vitro and in vivo T1-weighted MR imaging applications. In this work, LAP nanodisks were sequentially modified with silane coupling agents, succinic anhydride to have abundant carboxyl groups on their surface, and amine-terminated poly(amidoamine) (PAMAM) dendrimers of generation 2 (G2). The dendrimer-modified LAP nanodisks were then conjugated with gadolinium (Gd) chelator diethylenetriaminepentaacetic acid (DTPA), followed by Gd(III) chelation to form the LM–G2–DTPA (Gd) nanocomplexes. The designed LM–G2–DTPA(Gd) nanocomplexes were characterized via different techniques. Cell viability assay shows that the formed LM–G2–DTPA(Gd) nanodisks are non-cytotoxic in the given concentration range. With a high r1 relaxivity (2.05 mM1 s1), the LM–G2–DTPA(Gd) nanocomplexes are able to be used as an efficient contrast agent for T1-weighted MR imaging of cancer cells in vitro and animal organ/tumor model in vivo. The designed LM–G2– DTPA(Gd) nanocomplexes may hold a great promise to be used as a versatile nanoplatform for MR imaging of different biological systems.

Day 2 :

Biography:

Ziyad S. Haidar is a Full Professor of Biomaterials and Tissue Engineering and the Scientific Director of the Faculty of Dentistry, Universidad de los Andes in Santiago de Chile. Concurrently, he is the Founder and Head of the Biomaterials, Pharmaceutical Delivery and Cranio-Maxillo-Facial Tissue Engineering Laboratory/Research Group (BioMAT'X Chile; please visit: http://www.uandes.cl/facultad-de medicina/biomaterials-pharmaceutical.html). Haidar also serves as the Head of Innovation at the Centro de Investigación e Innovación Biomédica and a Faculty member in the Doctoral Program (BioMedicine) at the Facultad de Medicina. He is a Visiting Professor at several institutions, such as the Division of MaxilloFacial Surgery at the Universidad de la Frontera in Temuco. Haidar is a trained dentist, implantologist and an oral and maxillofacial surgeon with a PhD in nanobiomaterials, pharmaceuticals and tissue engineering from McGill University, Montréal, Canada. He is an international speaker with more than 125 publications, conference proceedings, text-books and patents and is an editorial board member of several national and international peer-reviewed scientific journals / periodicals. 

Abstract:

Statement of the Problem: Despite significant improvements, in reconstruction techniques and materials, during last decades, the regeneration, restoration and/or repair of oro-dental and maxillo-facial defects remains a challenge. Platelet Concentrates (PCs) are autologous blood extracts obtained through centrifugation of whole blood samples. The preparation procedure allows the gathering and concentration of platelets and other therapeutic blood constituents (fibrinogen/fibrin, growth factors, leukocytes and circulating cells), in clinically-usable preparations (surgical adjuvants), which may enhance, accelerate and promote tissue (hard and soft) wound healing and regeneration. Despite promising clinical observations, their overall effectiveness remains debated, to date. Today, it can be safely stated that, in oral and maxillofacial surgery, the Leukocyte and Platelet-rich Fibrin (L-PRF) sub-family is receiving the utmost attention, mainly due to simplicity, user-friendliness, malleability and potential cost-effectiveness, yet with outcome unpredictability.

Aims: Prepare, characterize, and evaluate a novel L-PRF bioscaffold incorporating human gingival mesenchymal stem cells and natural polymer-based nanoparticles capable to induce in situ healing and de novo local bone formation for its potential clinical application as a dental extraction socket preservation alternative strategy, immediately post-exodontia.

Materials and Methods: The resulting bioscaffold was characterized for its physico-chemico-mechanical and cytocompatibility/osteogenic properties, in vitro, followed by biocompatibility, malleability and efficacy, in vivo, in a challenging critical-sized defect model in the crania of normal WISTAR rats. Timely bio-distribution assays were performed. Histopathological, histomorphometrical and immunohistochemical evaluation and analysis followed.

Findings: Together, the results obtained show that is possible to formulate a safe, stable and biodegradable bioscaffold with intrinsic osteogenic potential as an advantageous alternative strategy for bone repair and regeneration.

Conclusion & Significance: Autologous L-PRF is often associated with early bone formation and maturation; accelerated soft-tissue healing; and reduced post-surgical pain, edema and discomfort. Indeed, measurements of volumen, density and area of the newly-formed bone in the defects together with the clinical observation of animals, showed a significant increase on the quantity and quality of the new bone when the defects were filled with the bio-scaffold, when compared to controls. A better analysis of rheological properties, bio-components and bioactive function of the nanoL-PRF preparation would enhance the cogency, comprehension and therapeutic potential of the reported findings; a step closer towards a new era of “super” oro-dental and maxilla-facial biomaterials and tissue engineering scaffolds.

Keynote Forum

Michal M. Godlewski

Warsaw University of Life Sciences, Poland

Keynote: Multimodal nanoparticles for medical applications

Time :

Biography:

Abstract:

Cancer diseases prompt an enormous medical challenge for the highly-developed countries. The increasing life-span and epidemic of civilisation-related diseases, combined with the ever decreasing quality of the environment cumulates the exposure risks and potential for cancer development. Currently, cancer-related deaths may for the first time in history become the major cause of death in the developed countries. Furthermore, current diagnostic and therapeutic strategies are inadequate, as they are commonly failing to detect small tumours, metastases and eradicate them.

Exponentially growing field for research in the nanomaterials prompts an enormous potential of possible applications of nanoparticles in medicine. We focused on the applications of biocompatible, high-k oxide, nanoparticles (NPs) in the field of cancer diagnosis and therapy. This work was focused on the potential development of multimodal detection-therapeutic system with dopant-dependent contrasting properties in the magnetic and fluorescent resonance.

Mice received suspension of hydrothermally created nanoparticles (10 mg/ml, 0.3 ml/mouse) via gastric gavage. All protocols were according to the EU guidelines and approved by 2/2012 and 13/2015 LEC agreements. Following oral administration, nanoparticles were passively targeted to all tumour tissues most probably by enhanced permeation and retention (EPR) effect. In the lungs NPs were targeted specifically to the areas of metastases making them a highly specific diagnostic tool for cancer in this tissue.

  • Impact of Nanomedicine on Health Care | Future Concepts in Nanomedicine | Nanomedicine in Cancer Therapeutics

Session Introduction

Roland H. Stauber

University Medical Center of Mainz Germany

Title: PATHOGEN-NANOMATERIAL CROSSTALK: PRINCIPLES AND RELEVANCE OF NANOANTIBIOTICS

Time : 12:20-12:50

Speaker
Biography:

Abstract:

Nanomaterials have dramatically increased in functionality and complexity, potentially allowing also unprecedented control over microbial pathogens, such as bacteria, fungi, or viruses. From these advances arises the prospect of novel nanomaterial-based antimicrobial therapies, which clearly differ from their bulk counterparts. Yet, practi­cal constraints require a rational understanding of NMs' physico-chemical characteristics and parameters at the nano-bio interface that impact their antimicrobial activity. We here define the most important nanomaterial parameters and biological outputs enabling controllable antimicrobial activity, while minimizing the complexity of designs. We present the problematic of nanomaterial resistance and mechanistic strategies to overcome these current limitations for next-generation practical applications. The presented insights will inspire nanomaterial designs that maximize functionality and safe translatability as new nanoantibiotics, and deepened our understanding on the biomedical and ecological relevance of nanomaterial-microbiota cross-talk in general.

Speaker
Biography:

Abstract:

We report results of the studies relating to fabrication of the sensing platform for development of label free electrochemical immunosensor based on graphene (Gr) and copper sulfide (CuS) composite and further poly p-phenylenediamine and graphene nanocomposite (PPD-GR). Graphite screen-printed electrodes (SPEs) modified with CuS-GR and PPD-GR nanocomposite and applied to advance label-free and non-enzymatice electrochemical immunosensor for quantitative determination of protein biomarker carbohydrate antigen 15-3 (CA15-3) and neuron-specific enolase (NSE), respectively. CuS-GR nanocomposite shows excellent electrocatalytic activity towards catechol as probe, which improve the sensitivity of the immunosensor. Also, It was found that the PPD-GR nanocomposite exhibits excellent electrocatalytic activity towards ascorbic acid (AA) oxidation as analytical signal based on EC′ mechanism. The CuS-GR based immunosensor exhibited a wide linear range of 1.0–150 U mL-1, with a low detection limit of 0.3 U mL-1 toward CA15-3. In the case of PPD-GR nanocomposite based immunosensor due to the excellent electrocatalytic activity of PPD-GR nanocomposite, determination of NSE antigen was based on its obstruction to the electrocatalytic oxidation of AA after binding to the surface of electrode through interaction with the anti-NSE. The proposed immunosensor exhibited a wide linear range of 1.0–1000 ng mL-1, with a low detection limit of 0.3 ng mL-1 toward NSE. These developed immunosensor showed good specificity, accuracy, stability and it was successfully applied for the determination of CA15-3 and NSE in real samples. The CuS-GR and PPD-GR nanocomposite materials-based immunoassay provides a promising sensitive biosensor approach for clinical applications.

  • Young Research Forum

Session Introduction

Martin Quirke

Dublin Institute of Technology Ireland

Title: Next generation Nano enabled antibiotics

Time : 14:20-14:45

Speaker
Biography:

Martin Quirke went onto study third level in Dublin Institute of Technology were he graduated with a first class honours degree in Science and Nanotechnology majoring in physics. The title of his PhD project is “Next generation nano antibiotics”. The main focus of study is the antimicrobial capabilities of water stable C60 fullerenes and whether or not they can act as a viable drug delivery system to treat pathogenic MDR bacteria, such as E.coli and MRSA. He was very much accustomed to physics given it was always his favoured subject so he gathered a PhD project outside my comfort zone would be fun.  He is currently in the final year of his PhD studies and coming to the end of what has been a long 10 year plan. From second level education, to third and finally forth, a PhD has been the main goal. 

Abstract:

The objective of my research was to design, synthesise and tailor a nanoparticle-antibiotic conjugate capable of a multi-targeted approach to MDR pathogenic bacterial infections. Post-synthesis the mechanisms of interaction between the conjugate and the bacteria will be elucidated, to allow for refinement and optimisation of the multi-targeted approach. This work will develop new methodologies and standards for testing the antimicrobial properties of novel nanomaterials.

 

Speaker
Biography:

Dr. Nefeli Lagopati studied Physics (BSc), Medical Physics (MSc), Advanced Materials (MSc) and Biology (PhD). She works as a postdoc researcher at the National Technical University of Athens, School of Chemical Engineering, and at Molecular Carcinogenesis Group, School of Medicine, University of Athens, where she additionally works as an adjunct lecturer, teaching “Cancer Biology”. Her research interests include the multidisciplinary field of nanomedicine in cancer treatment. Specifically, she focuses on the possible apoptotic effect of nanomaterials on breast cancer cells (IKY Scholarship). In the past, she had worked on (European) research projects, related to dosimetry in nuclear medicine, radiobiology - investigation of chromosomal alterations due to radiation, biochemistry of ROS-induced glutathionylation and evaluation of the role of iron ions, development of drug delivery systems and biomaterials, based on hydroxyapatite and chitosan, Monte Carlo Simulation etc. She is also a classical guitarist (BSc) and loves art and travelling

Abstract:

The scientific community approaches the multivariate condition of cancer disease in many ways. There are still aspects of the research field of alternative cancer treatments that remains to be discovered, focusing on minimize the undesirable consequences of the conventional treatment methods. It is now well established that when TiO2 nanoparticles are photo-excited, the photon energy generates pairs of electrons and holes which react with water and oxygen to yield reactive oxygen species (ROS) which can damage cancer cells. Therefore, TiO2 is a promising photosensitizer against cancer.

The aim of this study is the development of TiO2 nanoparticles with the potential to photo-induce anticancer effect via the mechanism of oxidative stress upon irradiation with visible light. Surface modification by doping with metal ions improves TiO2 photocatalytic activity. This process leads to reduction of electron-hole recombination, resulting in efficient separation and stronger photocatalytic reactions. Particularly, silver is an important dopant, which up-regulates TiO2 biological activity.

Thus, Ag-doping of TiO2 was undergone, followed by detailed characterization (XRD, micro-Raman, SEM). Cultured MCF-7 and MDA-MB-468 breast cancer epithelial cells were irradiated, using visible light, in the presence of Ag-doped TiO2 aqueous dispersion. Cell viability was estimated, by MTT colorimetric assay. Western blot analysis of protein expression and characterization, as well as DNA laddering assay were used to investigate the existence of cell apoptosis.

We demonstrated that Ag-doped TiO2 nanoparticles induced apoptosis specifically in the highly malignant MDA-MB-468 cancer cells. MCF-7 cells were still unaffected, under the same circumstances. The molecular mechanism of TiO2 nanoparticles cytotoxicity was associated with increased pro-apoptotic Bax expression and caspase-mediated poly (adenosine diphosphate (ADP)-ribose) polymerase (PARP) activation thus resulting in DNA fragmentation and programmed cell death.

Further studies are already in progress, focalizing at the development of visible-light-excited co-doped TiO2 nanoparticles with silver and nitrogen, for targeted cancer therapy. 

Reid Grimes

University of Oklahoma Louisiana

Title: Bi-Functionalized Clay Nanotubes for Anti-Cancer Therapy

Time : 15:10-15:35

Speaker
Biography:

Abstract:

Systemic toxicity is a significant drawback to a majority of chemotherapeutics currently on the market.The current research regarding multifunctional nanoparticles containing both a diagnostic and therapeutic functionality have demonstrated promise.Halloysite clay nanotubes (HNTs) are naturally forming nanoparticles with documented drug delivery applications.Recently, the synthesis of an HNT nanoparticle with both folic acid (FA) and fluorescein isothiocyanate (FITC) has been reported.The uptake of the functionalized nanoparticle into CT-26 murine colorectal cancer cells was observed through epi-fluorescent and phase contrast microscopy.HNTs have demonstrated the ability to act as a nano-container for pharmaceutical agents.The addition of a therapeutic agent to the system is currently being tested, and this presentation will outline results of the trials.Furthermore, the modification of the outer surface of HNTs with photothermal agents will be discussed.The modified HNT system described in this presentation provides a viable theranostic system for a more effective treatment option.

 

  • Poster Presentation
Speaker
Biography:

Thomas is a final year PhD student based at Leeds Beckett University, Leeds (UK) and has been working within the School of Clinical and Applied Sciences since 2014. Thomas received a BSc (hons) in Biology from the University of Derby in 2011, and an MSc in Molecular and Cellular biology from Sheffield Hallam University in 2013. Thomas’ research interests include nanotechnology and nanobiotechnology, with a focus on how these technologies can be used to improve the treatment of cancer.

 

Abstract:

Cancer is a leading cause of death globally. Whilst current approaches to treatment are effective, they are accompanied by significant side effects. Gold nanoparticles (AuNP) have been explored for their potential use as chemotherapeutics. AuNP’s induce hyperthermia in response to excitation by near infrared light (NIR), which then can induce apoptosis in a controlled manner. CD59, an 18–22kDa membrane protein responsible for the inhibition of complement, is over expressed in multiple cancer sites, is associated with poor prognosis (Rolland et al 2008) and is a potential target molecule for cancer treatment. Here research is presented relating to the ability to achieve controlled cell viability reduction using anti-human CD59 targeted gold nanoparticles. 

AuNP’s (1.25µg/ml-20µg/ml) were shown to reduce HeLa cell viability in a concentration-dependent manner as assessed using MTT assay. Inclusion of polymer (PEG) coating significantly reduced (p<0.05) the impact on cell viability.  Interestingly, CD59 expression was reduced significantly following exposure to AuNP’s compared to PBS controls when assessed using fluorescent microscopy, this impact being negated by PEGylating the AuNP’s.  Further modification to conjugate an anti-human CD59 monoclonal antibody (AuNP - MaB) resulted in additional reduction in nanoparticle-induced cytotoxicity. HeLa cells treated with a combination of AuNP-MaB’s and NIR light (519/520nm) led to significant reduction in cell viability compared to untreated PBS controls (p<0.01) and untargeted AuNP (p<0.05) controls. CD59 knock down HeLa’s exhibited increased sensitivity to both unmodified and targeted AuNP’s compared to normal HeLa’s, suggesting a protective role for CD59.

Data presented here suggests that CD59 provides a stable anchor point, allowing for induction of hyperthermia associated cytotoxicity through NIR treatment. Reducing CD59 expression levels in response to AuNP exposure, along with increased sensitivity of CD59 deficient cells, indicates that PEGylation to improve biocompatibility of AuNP’s is required before they should be considered for treatment in this manner.

Speaker
Biography:

Abstract:

Diabetes is a defect in the body’s ability to convert excess glucose to glycogen. Two classes of antidiabetic drugs were identified and nateglinide is a sub-division of oral antidiabetic drugs belonging to Meglitinides family. Gaussian 09 code which use density function theory as working principle was used to study the geometric, infrared, Raman, 1H-NMR, 13C-MNR spectrum and density of state of the nateglinide antidiabetic drug using exchange functional B3LYP/6-311G. For the geometry optimization, it was observed that, there is appearance of a new additional bond between C12 and N4 which changes the natural nature of both 1H-NMR and 13C-NMR spectra. For infrared and Raman spectra, functional groups and polarizability were observed. However, the result of density of state shows the large band gap of 5.46758eV and most of the orbitals were occupied at lower valance band.

Keywords: Nateglinide, Infrared, 1H-NMR, 13C-NMR, Density of state (DOS) and Raman Spectra.

 

Speaker
Biography:

Mrunal Patil has expertise in designing, formulating and evaluating lipid carriers for the treatment of fungal diseases. She has developed lipid-drug combination after years of learning fungal drug resistance patterns in K.E.M hospital and designing formulations at Institute of Chemical Technology. She has been awarded Newton Bhabha fellowship for carrying out research work in mechanism elucidation of active aminolipid carrier at Nottingham University, UK. She has a keen interest in design and developing safe, efficacious lipid-based Nano-formulation for resistant infectious diseases and is looking forward for more challenges in the said field.

Abstract:

Management of invasive candidiasis in immune compromised patients exhibits a major challenge for the clinicians since, antifungal monotherapy becomes ineffective. Moreover, switching between new antifungal agents and drug combinations intensify the situation by creating parallel adverse effects and drug toxicities. Furthermore, combining two drugs in a unit dosage form bring pharmaceutical challenges. This in turn, decreases the pharmacoeconomic efficiency in treatment associated with drug resistant candidiasis. Hence, we suggest replacing drug-drug therapy with drug-active lipid therapy,wherein the active lipid is a synthesized aminolipid based multifunctional carrier (PFA 18) which exhibit combinatorial synergy with existing first line antifungal agents like fluconazole and polyenes such as amphotericin B against clinically isolated drug resistant Candida species. As suggested by our computerized simulation studies, this lipid forms a strong hydrophobic and van der Waals interactions with antifungal agents supporting its stabilization into a nanoemulsion system. Sensitivity testing against gene deleted S. cerevisiae library also represented a possibility of effect on mitochondrial outer membrane and cell membrane of yeast. These activities were confirmed by flow cytometric mitochondrial assay and topographical cryoimaging studies. In vitro cytotoxicity confirmed that PFA 18 alone and in combinations with fluconazole/ amphotericin B did not show any cytotoxic effect on Hep2G or HEK cell lines. Moreover, in vivo acute toxicity testing of PFA 18 showed that its toxicity range lies between 200-300 mg/kg. In vivo efficacy studies in swiss albino mice model infected with multidrug resistance candida revealed that, PFA 18 played a major role in reducing drug dose, and toxicity thereby increasing the probability of survival.

 

Speaker
Biography:

Fereshte Damavandi is currently a PhD student in Chemical and Material Engineering Department, University of Alberta. Before starting her PhD, she obtained his MSc and BSc degrees both in the field of chemical engineering from Amirkabir University of Technology, Tehran, Iran.

Abstract:

Detection of low abundant target DNA in the cases of viral infections, tumor characterization, disease prognoses, transplantations and many more are extremely difficult due to the fact that these low abundant target sequences are buried in huge human genomic background. Therefore, DNA separation is mostly coupled with either primer-based amplification or probe based capture methods. Probe based capture method, such as using streptavidin coupled magnetic beads, however, does not increase the DNA capturing efficiency because of high level non-specific interaction. In order to overcome this limitation, we redesign the surface chemistry of capture beads by applying click chemistry. Other than the most commonly used streptavidin-biotin interaction, click chemistry employs Cu[I]-catalyzed azides-alkynes Huisgen cycloadditions (CuAAC) lead to stable and rigid triazole linkages. Along with inert silica surface coverage, triazole linkers could effectively reduce any possible non-specific interaction. Moreover, CuAAC reaction is fast, high-yielding, and highly tolerant of a variety of functional groups. It performs efficiently in aqueous media and generates stable products in the face of heat and denaturation agents. We firstly prepared magnetic nanoparticles (nanoclusters) with silica core-shell and designated super-paramagnetic behavior. In a second step, we introduced azide groups onto the surface of magnetic nanoparticles as the functionalization layer for click chemistry. Finally, we applied CuAAC click reaction for a facial and high efficient cross-linking of oligonucleotides to the silica surface. The physicochemical properties of the particles such as size, morphology, magnetic properties, crystallinity, DNA loading fully characterized by using SEM, TEM, VMS, XRD, XPS, and FT-IR techniques. The characteristic tests and DNA isolation experiments show that a biocompatible nanocluster with a dense monolayer of oligonucleotide were generated with increased the DNA capturing efficiency and decreased the non-specific interaction.