Day 2 :
- Nano Pharmaceuticals| Nanobiotechnology| Graphene Medicine| Personalized Nanomedicine| Regulatory Aspects Towards Approval of Nanomedicine and Pharmaceutical
Location: Meeting Place 2
University of South Australia, Australia
University of South Australia, Australia
Hugo Albrecht is a Senior Lecturer at the University of South Australia and a Member of the Centre for Drug Discovery and Development within the division of Health Sciences. Prior to his appointment to the University of South Australia, he has held various positions in academic and commercial settings in Switzerland and the US, where he gained profound experience in preclinical drug discovery.
For a long time, prostate cancer has been considered chemo-refractory. Only during the last 10-15 years, have good results been achieved in clinic trials with taxane derivatives such as docetaxel (DTX) and cabazitaxel. However, disabling toxicities including fatigue and neuropathy limit optimal dosage and therefore only modest, life prolonging effects have been achieved for prostate cancer patients. Future treatment outcomes might potentially be improved through targeted delivery of chemotherapeutic compounds into cancer cells while reducing the exposure of healthy tissue. Prostate cancer cells frequently overexpress the gastrin releasing peptide receptor (GRPR) and various strategies have been applied in preclinical settings to target this receptor for the specific delivery of anti-cancer compounds. Recently, it has been proposed that elastin-like polypeptide (ELP)-based, self-assembling micelles with tethered gastrin-releasing peptide (GRP) on the surface might be useful for active targeting of prostate cancer cells. Although poorly soluble chemotherapeutics such as docetaxel have been loaded into the hydrophobic cores of ELP micelles, only limited drug retention times have been achieved. We report the generation of hybrid ELP/liposome nanoparticles which self-assemble rapidly in response to temperature change, encapsulating docetaxel at high concentrations with slow release. The GRP ligand was displayed on the surface and specifically bound to GRP receptor expressing PC-3 cells as demonstrated by flow cytometry. This novel type of drug nanocarrier was successfully used to reduce cell viability of prostate cancer cells in vitro through the specific delivery of docetaxel.
Figure: Specific targeting of prostate cancer cells with hybrid ELP/liposome nanoparticles.
1. Zhang W, Garg S, Eldi P, et al (2016) Targeting prostate cancer cells with genetically engineered polypeptide-based micelles displaying gastrin-releasing peptide. Int J Pharm. 513 (1): 270-279.
2. Shi P, Aluri S, Lin YA, et al (2013) Elastin-based protein polymer nanoparticles carrying drug at both corona and core suppress tumor growth in vivo. J Control Release. 171 (3): 330-338.
3. Na K, Lee SA, Jung SH, Hyun J and Shin BC (2012) Elastin-like polypeptide modified liposomes for enhancing cellular uptake into tumor cells. Colloids Surf B Biointerfaces. 91: 130-136.
4. Pereira S, Egbu R, Jannati G and Al-Jamal WT (2016) Docetaxel-loaded liposomes: The effect of lipid composition and purification on drug encapsulation and in vitro toxicity. Int J Pharm. 514 (1): 150-159.
5. Naguib YW, Rodriguez BL, Li X, Hursting SD, Williams RO 3rd and Cui Z (2014) Solid lipid nanoparticle formulations of docetaxel prepared with high melting point triglycerides: in vitro and in vivo evaluation. Mol Pharm. 11 (4): 1239-1249.
Iran University of Medical Sciences, Iran
Bita Rasoulian has completed her graduated from Maziar University, Royan, Mazandaran in the field of Biomedical Engineering, Biomaterials in Bachelor degree on 2017. She is a Research Assistant of Nanomedicine under Supervision of Dr. Shima Tavakol at Cellular and Molecular Research Center, Iran University of Medical Science. However, she is interested in the investigation of nanomaterials and their influence and interaction with biological systems especially nervous and bone. Meanwhile, she has expertise in in-vitro and in-vivo studies, as well. Her major researches has been on spinal cord injuries and craniofacial injuries, modeling and treating them with various specified nanomedicines in which she has gained exclusive results.
Bone is a real nanocompsite of nanofibers and nano ceramics and approximately 600,000 suffers from craniofacial deficits in US. RADA as a core of self-assembling peptides exhibits an acidic pH while the pH of KSL is higher than RADA. The acidic pH of RADA usually is an obstacle in tissue engineering but by regards to the acidophilic nature of bone, it was investigated for the first time. In the present investigation, for the first time the BMHP motif was bound to the RADA and KSL as a core of self-assembling peptide nanofiber and was evaluated its cell viability, ROS, NO and LDH release on MG-63 cell line as a cell line of bone osteosarcoma and then its effects was evaluated as a gene expression of apoptotic and integrins. Then, they were implanted in a critical size bone defect in rats for two month and densitometry of bone defects were analyzed and compared. Results showed that KSL core due to higher cell viability, BCL2 gene over-expression and less intracellular ROS production was more effective than RADA ones in bone regeneration. However, KSL showed higher cell membrane damage and BAX gene over-expression than RADA. These data were in good agreement with X-ray radiographic data that disclosed higher bone density in KSL nanofiber than RADA. Based on the presented data since KSL induced higher nerve regeneration (not shown) and bone regeneration it is a good candidate for spine repair that its biodegradation will improve motor neuron recovery, as well.
Immunology Theodor Bilharz Research Institute, Egypt
Manal M Kamel is a Professor of Immunology at Theodor Bilharz Research Institute (TBRI), Giza, Egypt. She has graduated from the Faculty of Medicine, Cairo University. Her Postgraduate studies were in Immunology and Clinical Pathology. She has a great experience in the fields of antigen preparation, nanotechnology, monoclonal production, CB MSCs transplantation. She has supervised (9) MSc and PhD thesis, two of them in the field of nanotechnology with stem cells and monoclonal antibodies. She has published more than 23 papers in reputed journals and has been serving as Member in the selected referee lists of: The International Journal of Immunological Studies-Cell proliferation.
MSCs were generated and propagated from umbilical cord blood (UCB) and characterized by immunophenotyping using flow cytometry. Hepatogenic differentiation was induced on 2D and 3D (nanofiber scaffold) culture system. Gene expression analysis was done by real-time PCR. Human albumin and α-1 antitrypsin (AAT) in cell culture supernatants was performed by ELISA. Differentiated cells were administered intravenously into a murine model of CCL4 induced liver cirrhosis. Animal models were divided into three groups, a) Pathological control, b) CCL4 treated with hepatogenic differentiated MSCs on 2D vessels, c) CCL4 treated with hepatogenic differentiated MSCs cultured on nanofiber scaffold (3D). Liver pathology was examined 12 weeks after treatment with cells. The hepatogenic differentiated MSCs stained positively with more abundant and mature cells with hexagonal shape and central nuclei forming large sheets in 3D than 2D at day 28. By scanning electron microscopy hepatogenic differentiated cells showed strong adherence and penetration onto the surfaces of the nanofibrous scaffolds. (AAT) secretion and indocyanine green uptake on day 21 was significantly increased in 3D rather than 2D. In experimental model, MSC-3D scaffold group stained with Sirius red and Masson Trichrome exhibited maximal restoration of liver architecture with absent septal fibrosis. In contrast, hepatic fibrosis decreased to a lesser extent in MSC-2D group. Liver function tests revealed marked improvement of ALT, AST in 3D treated group. Both 3D and 2D culture system are effective in functional hepatogenic differentiation and serve as a suitable vehicle in liver tissue engineering. In vivo hepatogenic differentiation is more effective on 3D nanofibrous scaffold, with better functional recovery.
Flemish Institute for Technological Research, Belgium
Delivery of therapeutic nanoparticles (NPs) by stem and progenitor cells can overcome the limitations of NP carriers and can create opportunities for stem cell transplantation. In this respect, we studied the interaction between engineered NPs and ex vivo derived hematopoietic progenitor cells (HPC). CD34-positive HPC were derived from human cord blood and were exposed to fluorescent carboxylate polystyrene NPs of 40, 100 and 200nm size, and to 50nm SiO2 NPs. NP uptake kinetics were assessed by measuring fluorescence intensity at short time intervals using flow cytometry. HPCs demonstrated a rapid (within 1 hour), but transient loading behavior which was retained upon changing the size and composition of the NPs. Using confocal microscopy fluorescent NPs were observed to appear mainly at the outer boundary of the cells, while only few were located in the intracellular compartment. These findings contrast with reported observations of steadily increasing NP internalization in other cell types, such as phagocytic cells or cell lines, and suggest that CD34+ progenitor cells handle NPs by using different mechanisms. Further research will be conducted to investigate the processes underlying the interactions between the NPs and the cellular membrane.
In 2014 I obtained a Master’s degree in biomedical sciences with a specialization in bio-electronics and nanotechnology at the university of Hasselt. In 2015 a started a joint-PhD between Hasselt University and VITO. VITO is a technological research institute working for the Flemish government.
NanoBioMedical Centre, Adam Mickiewicz University in Poznan, Poland
Artur Jędrzak received the M.Sc., Eng. degree in Organic Chemistry in 2016 at Poznan University of Technology. Since 2016 he is a Ph.D. student of Chemical Technologyat Poznan University of Technology and he is also a member of NanoBioMedical Centre in Poznan. His research interests are biosensors, enzymatic and catalytic systems and synthesis of hybrid/composite materials for nanomedicine.
Current development of nanotechnology influences on a synthesis of novel and more efficent drug carriers for nanomedicine, especially in cancer treatment. The application of specific nanomaterials like dendrimers PAMAM is currently a prominent topic in cancer therapy due to their internal cavities, water solubility, and modifiable surface functionality rhat render them as interesting carrier for drug delivery .
The other most commonly used material in cancer treatment are magnetic nanoparticles of iron oxide. In particular, the magnetite (Fe3O4) nanoparticles has drawn a lot of attention since they are biocompatible, nontoxic, size/shape-tunable and they havehigh surface/volume ratio and allow easy separation from mixtures by application of an external magnetic field. Morover, that magnetite can be used as contrasting agents in nuclear magnetic resonance imaging (MRI), thus they arean ideal component to construct advanced teranostatic-nanotools. Further, polydopamine (PDA) coated magnetite exhibit high photothermal properties and they are recently extensively investigated in cancer treatemnt.
Here we present, the PAMAM dendrimers grafted to the PDA a coated magnetic nanoparticles as atractive theranostic for dual chemo- and phothermal theraphy. Obtained Fe3O4@[email protected] nanocarriers were characterized by means of TEM, zeta potential, FT-IR, XPS, magnetic meseremnsts and MRI. Further the results regarding drug loading and it release profile will be discussed as well as their application in vitro in combined chemo- and phothermal theraphy of liver cancer.