Day 2 :
University of Wisconsin ,USA
Time : TBA
Shaoqin Sarah Gong is a Vilas Distinguished Achievement Professor in the Department of Biomedical Engineering and the Wisconsin Institute for Discovery at the University of Wisconsin–Madison. Prof. Gong’s research group has developed a series of multifunctional drug/agent nanocarriers including unimolecular micelles, polymer nanocapsules, polymer vesicles, and polymer-functionalized inorganic nanoparticles for targeted drug/agent delivery to treat and monitor various major health threats including cancers, vascular disorders, and eye diseases. She has co-authored over 140 peer-reviewed journal articles and more than 130 conference papers. Her H-index is 49. She is an editorial board member for several journals including Biomaterials, Theranostics, Biofabrication, and Nanotheranostics. She also served as an Associate Editor for Biomaterials and is the winner of a number of awards including the NSF CAREER Award and NIH Career Development Award
Drug nanocarriers have received increased attention because they can greatly enhance the therapeutic efficacies of drug payloads. Conventional polymer micelles, formed by the self-assembly of multiple linear block copolymers, are one of the most widely studied drug nanocarriers. However, one major concern with these conventional polymer micelles is their poor in vivo stability due to the dynamic nature of the self-assembly process. Premature rupture of these drug nanocarriers during circulation can cause a burst release of payloads into the bloodstream, which can lead to potential systemic toxicity and surrender their targeting and/or imaging abilities, thereby largely limiting their in vivo applications. Unimolecular micelles — formed by single/individual multi-arm star amphiphilic block copolymers — have been investigated to overcome this drawback. Because of their covalent nature and unique chemical structure, properly engineered unimolecular micelles can possess excellent in vivo stability (Figure 1). Moreover, due to their excellent chemical versatility, these unique unimolecular micelles can be tailored with different targeting ligands (e.g., small molecules, peptides, antibodies, nanobodies, or aptamers) and/or imaging probes (e.g., fluorophores, radioisotopes, or MRI contrast agents) to achieve multifunctionality. In particular, we have successfully developed a series of multifunctional unimolecular micelle platforms for targeted cancer (e.g., breast cancer and neuroendocrine cancer) theranostics. We have also engineered unique unimolecular micelles to treat glaucoma as well as vascular diseases (e.g., intimal hyperplasia attenuation) in a targeted manner. Moreover, other than small drug molecules, siRNA, peptides, and small proteins have also been successfully delivered via unimolecular nanoparticles through electrostatic interactions. In summary, unimolecular nanoparticles are a promising drug nanocarrier that warrants further investigation for a broader range of potential applications
- Drug Delivery Research
Location: Hilton Tokyo Narita
Weizmann Institute of Science, Israel
Dr. Lilach Agemy has her expertise in vascular biology and tumor/ atherosclerosis microenvironment. Developed highly specific delivery of different probes and drugs for cancer/ atherosclerosis therapy with hands on experience in the synthesis, modification, and characterization of different nanoparticles systems including magnetic iron based nanoparticles. Her current research focuses on using new targeted derivatives for photodynamic therapy with bacteriochlorophyll that were developed in our lab and based on TOOKAD, which was recently approved by EMA. Dr. Agemy is working in an extensively multidisciplinary environment involving Biologists, Chemists, Physicists and Bioengineers with participation ranging from designing, performing experiments, analyzing imaging and other biological data, and is involved in training graduate students and postdocs.
Cytotoxic drugs that target specific receptors on cancer cells and supporting vasculature often fail to convey significant therapeutic benefit, despite their extensive tumor uptake and high toxicity in cell cultures. A recent example is provided by Cilengitide®, a cyclic Arg-Gly-Asp (cRGD) that accumulate in tumors but fails to delay cancer progression. In this study we rationalized the current failure of cRGD based clinical trials by assessing the tumor heterogeneity, showing that significant populations of cancer and endothelial cells do not accumulate the cRGD agents. We further tested the hypothesis that bystander cell death propagation initiated by agents coupled to cRGD molecules can effectively eradicate the entire tumor even if taken by the limited cell populations. The new approach was applied to mice grafted with metastatic 4T1 tumors in their mammary pad. This model is considered good representative for triple negative breast cancer (TNBC), a heterogeneous disease with distinct molecular subtypes that differentially respond to chemotherapy and targeted agents with high rate of treatment failure and mortality.
Results: Using STL-6014, a cRGD tagged with a fluorescing and photoactive bacteriochlorophyll derivative (Bchl-D), we showed that STL-6014 can specifically and noninvasively target orthotopic TNBC tumors as well as lung metastatic tumor lesions trough integrin receptors expressed on different cell populations. The apparent high tumor uptake reflects the integrin expression by these cells. High cRGD uptake confers death of cancer and stroma cells while cells lacking integrin expression remains alive and drive tumor proliferation. This therapeutic obstacle is solved by self-promoting death signal initiated by photo-activation of the Bchl-D tags in the β3 expressing cells. Rapid propagation of cell apoptosis/necrosis via bystander effect results 62% primary tumor ablation in mice bearing 4T1.
Conceptual significance: The study provides rationale and new means for paradigm shift in cell-targeted therapies, understanding and overcoming failures of therapies that target specific cell populations in the tumor microenvironment.
The Maharaja Sayajirao University of Baroda,India
Sonal Thakore has completed her PhD at the age of 27 years from The Maharaja Sayajirao University, Baroda, Gujarat, India. She is assistant professor at The Maharaja Sayajirao University, Baroda, Gujarat, India and has 12 years of teaching experience. She has guided for 4 students for Ph.D. and published over 40 publications in reputed international journals. She has been granted Indian Patent No. 274199 dated 19/8/2010, “A process for synthesis of nanosized hydrophobic polysaccharide derivatives.” She has presented papers at several national and international conferences, served as reviewer for reputed international journals.
The design of stimuli responsive polymers is an emerging area in the field of medicine and biology, which makes use of practical and effective approach for treatment and eradication of several diseases. Based on the response triggered by conformational and structural modifications of polymers, they can be utilized for stimuli responsive applications. In order to elucidate the recent advances in the field the research carried out in the last decade is summarized. A summary of the variety of stimuli such as pH, temperature, enzyme, light etc. along with the relevant polymers used for their response thorough the corresponding triggering mechanisms will be presented. The future challenges and barriers for development of smart polymers will also be discussed.
Dr. Saeedeh Ghiasvand has completed her Ph.D. in molecular Genetic at the age of 27 years from Tarbiat Modares University. she is the assistant professor in biology department in Malayer University. she special areas of interest are phage display technology and targeted therapy
The discovery of ligands that selectively bind to a certain target plays a vital role in the generation of clinically relevant diagnostics and therapeutics. Phage display as a powerful methodology has proven very promising in the identification of many target specific ligands. But there is another aspect that phage can act as biomarkers. Phage colonized in the people bodies from the earliest moments of life and become our fellow travelers through the life. Phageome seems to be unique to each individual and alter in each different situations. phagosome structure and composition change depend on the physiological or pathological status of the body. Phageome oriented studies are vital to advance our understanding of the potential roles of phages in clinical application. The identification of phagosome as health or disease biomarker provides novel opportunities for unraveling the mechanisms underlying different diseases, stratifying patients, and developing more effective diagnostic and therapeutic approaches. Recent finding favor the suggestion that the phage might directly (phagosome that colonized in our body) or indirectly ( phage display technology) act as potential biomarkers for diagnosis and treatment.
University of Nottingham, Malaysia
Colon cancer is a crucial health problem worldwide. The current interventions combining surgery and chemotherapy have only partially addressed the issue of ineffectiveness and recurrence in patients . Traditionally most anticancer drugs are administered intravenously even for remote cases as in colon cancer, where residential presence of the anticancer drug at the colon is an obvious desirability. Thus, encapsulating drug loaded oral formulations that offer cancer-targeting capability are a promising alternative to improving treatment of colon cancer, whereby localised drug concentration is increased and side effects are minimised . Nanoparticles offer a rational choice due to its large surface area to volume ratio, but should withstand the milieu of the upper gut and deliver its cargo at the colon. In this view, we have developed a modified pectin-chitosancurcumin nanoparticle system (MCPCNPs) (Figure 1) for targeted delivery of curcumin to the colon. The MCPCNPs presented high mucoadhesion propensity in simulated colonic media and minimal at pH 1.2 (stomach). We further enhanced the MCPCNPs by coupling contamumab antibody that target the death receptor (DR5) present on the tumour surface, through a two-step carbodiimide (EDC) approach. The in vitro evaluation of the conjugation was examined using some available analytical techniques, while the conjugation efficiency was confirmed via the micro-bicinchoninic acid assay. The in vitro cytotoxicity and cellular apoptosis assays of the composite nanoparticle-antibody-curcumin-delivery system are being studied currently. In general, the data obtained so far strongly suggests that the formulated mucoadhesive, targeted curcumin-loaded nanoparticles have the potential to be applied as an orally deliverable colon cancer treatment