1. How are they made? Ethical Dilemmas Applications of Dendrimers in Gene Transfection What is a Dendrimer? Kyler Madara and Nicholas Yuhas Man-made nanoparticles that are synthetic chemical polymers, consisting of carbon-carbon bonds First synthesized by Fritz Vogtle in 1978 Resembles a hollow sphere, with a tree-like structure, similar to dendrites, after which they were named The interior gaps can be filled with drugs, genes, or any substance on the nano-scale Can be used in drug delivery and gene transfection Depending on the composition, different types of dendrimers have different purposes and functons Sustainable product due to the new human lives to be saved Drug Delivery Gene Transfection Gene transfection is the process of replacing faulty DNA in cells with new, correct DNA. This can potentially cure and effectively treat previously incurable genetic diseases. Disease Candidates Cycsic Fibrosis Cancer AIDS Parkinson's Disease Alzheimer’s Disease Cardiovascular Diseases Arthritis Diabetes The Process DNA segments are loaded in the dendrimer’s focal core This DNA segment will replace the DNA that is affected by a disease When the dendrimer reaches the desired cell, the dendrimer opens due to a change in pH The DNA binds to the original DNA and cuts out the problematic DNA that is coded for a certain genetic disease The disease is essentially cured, since the DNA programmed to express the disease is no longer present Chemical Warfare Critics argue that dendrimers can be loaded with toxic chemicals and used for warfare on the nanoparticle level When used as chemical weapons, dendrimers can be easily produced, transported and deployed Dendrimers can also serve as a stepping stone to a world of advanced warfare, if used for harmful purposes Biological Alteration As seen with gene transfection, dendrimers can be used to replace and edit segments of DNA This can lead to scientists “Playing God” by designing and altering the human genome Critics argue it is unethical to play with human biology Dendrimer TypeWhat is it? Polyamide Amine (PAMAM) Made using ammonia Mostly biomedical applications Glycodendrimers Sugar-based Drug delivery applications Chiral Contains a chiral center Drug delivery agent Polylysine Amino acid focal core Virus-like cancer treatment Liquid Crystalline (LC) Consist of carbosilane dendrimers Used in HIV treatment Phosphorus Phosphorus functionality Adapts an abnormal oval shape Polypropyleneimine (PPI) Butylenediamine core Can shrink and expand depending on the surroundings Protects drug from bodily defenses Stomach acid Enzymes Increases solubility and decreases toxicity (helps with cancer drugs) Helps with bioavailability Dendrimers cannot go through the kidneys Drug does not get filtered out of the body Cisplatin Toxic and nearly insoluble cancer drug Professor Ruth Duncan’s research group at Cardiff University used PAMAM dendrimers with Cisplatin Toxicity decreased Effective in treating melanoma Elizabeth R. Gillies (University of California, Berkeley) Created “bow-tie” dendrimer hybrids Completely non-toxic and biodegradable Considered to be a future drug delivery candidate Convergent Begin with the outside, and work inwards Easier to separate from byproducts Low yields when creating larger- generation dendrimers Easier to control Divergent Begin with the inside, and work outwards Harder to separate from byproducts High yields when creating larger- generation dendrimers Harder to control Williamson Ether Synthesis Biomolecular Nucleophilic Substitution (S N 2) Organic Compound swaps a good leaving group for an alkoxide nucleophile Creates an ether MichaelAddition Conjugated pi system reacts with carbonyl carbon Creates new carbon-carbon bonds Creates long chains