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• DiabetesThe 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 Type What 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 candidateConvergent

• 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 (SN2)• Organic Compound swaps a good leaving group for an alkoxide

nucleophile• Creates an ether

Michael Addition

• Conjugated pi system reacts with carbonyl carbon• Creates new carbon-carbon bonds• Creates long chains