GOLD NANOPARTICLES: A POSSIBLE CURE FOR PANCREATIC CANCER Erin Cannon, Madeleine Braun, and julia mcKay

Why Pancreatic Cancer? Pancreatic cancer cells can spread through the lymph nodes. The cancer cells grow and form into secondary tumors that can wrap around major organs and vessels. Ideally, the tumors would be removed surgically, but often they are too extensive Large portions of pancreas must be removed Symptoms appear in the later stages Limited test options Hereditary nature

The Problems with Chemotherapy and Radiation Low solubility Poor travel ability No effective target specification Kills healthy cells Invasive

What is Targeted Drug Delivery? An increase in concentration of drug in desired area while limiting it in other regions of the body Nanotechnology, including nanoparticles, are used as the vector of delivery Drug delivery systems account for fluctuating pH, temperature, and other chemical interactions High efficiency in treatment with fewer effects on unaffected areas of the body

Basic Properties of AuNPs Elemental gold: Conductor bio-compatible good surface chemistry Spherical Nanoparticles: high surface area to volume ratio Multimodal

Synthesis and Makeup of AuNPs Inogranic Core: Gold salt reduced in presence of stabilizing agent - Controls the physical behavior of the nanoparticle Organic Monolayer: -proteins and bio-molecules conjugated through favorable electrostatic reactions -drug attached to the surface of the particle with a ligand

The role of ligands in drug delivery Attach to a metal ion using coordinate bonding Covalent or non-covalent Bond occurs between functional groups and ligand Factors affecting the performance of ligands Binding affinity Surface density Half-Life

Drug Carriers to Tumor Sites Can be taken in orally or intravenously Occurs on different Levels: Specific Organs / Bodily Systems, Tissues, Specific Cells Chemotherapeutics delivered into cells to minimize effect on healthy cells Actively and Passively Targeted

Enhanced Permeability and Retention Due to characteristics of tumor vasculature itself Easy to permeate tissue at the site of angiogenesis Leaky vasculature, lack of lymphatic drainage, improper formation of vessels make is easy for nanoparticles to enter the tissue Nanoparticles become concentrated due to gaps Based on geometry of particle rather then chemical modification Passive

Surface Functionalization Targeting not possible without it Active form of targeting Commonly centered around tracking the Epidermal Growth Factor gene Surface coated with full/ fragments of antibodies Can also be coated with anti-EGFR peptides Ligand used to attach chemotherapeutic

Receptor Mediated Endocytosis The final step of delivery Surface groups of nanoparticle bind with those of cellular surface Cell engulfs many nanoparticles Bonds weak within cytoplasm and break Drug released and triggers apoptosis 50 nm diameter

Surface Plasmon Resonance Limited frequencies induce resonant conduction and lead to extinction (combination of absorption and scattering) Frequency at which maximum electron oscillation occurs Strong EM fields on the surface

Imaging of Cancerous Cells Nanoparticles act as “labels” on pancreatic cancer cells Limited frequencies induce resonant conduction and lead to extinction (combination of absorption and scattering) Darkfield Microscopy used to detect the AuNP labels

Photothermal Therapy Light at certain wavelength excites cells Energy loss through heat release Triggers hyperthermia in the tissue Cells 3-6 degrees Celsius higher than they should be Can kill cells or lead them to being more susceptible to death by other methods

Theoretical Process 2. Hyperthermia triggered 1. AuNPs permeate cancerous tissue (EPR and Active Targeting) 2. Hyperthermia triggered 3. Nanoparticles invade cells (Endocytosis) 4. Drug Release 5. Imaging of area treated

Technical Issues With AuNPs Aggregation Build up of particles in unwanted areas Prevented through modification of the monolayer Differences in Size The major benefit of AuNPs over other options is that they are multimodal Size affects Quantum Mechanics Drug Delivery Imaging of Cells Photothermal Therapy

Cytotoxicity: Concern for Sustainable Nanotechnology Nanoparticles remain within body post- treatment Could potentially cause harm to healthy cells within the body Molecular reaction with fluids within body Many experiments in process, very few long-term ones completely No clear answer yet

What other Nanoparticles are Being Researched? Polymeric Nanoparticles Made from complex, naturally synthesized molecules known as polymers Biocompatible, bio-degradable, cost-effective, versatile in composition Surface functionalized Disadvantages Batch-to-batch is hard to recreate Antigens can label it Need specific conditions Not multimodal

Conclusion Gold nanoparticles have the potential to revolutionize pancreatic cancer treatment Multimodal function Imaging Drug delivery Photo-Thermal Therapy Improve the quality of life and life expectancy for patients Future direction