Incoming and Outgoing Shipments in 1 STEP Using Odoo 17
Nano-Vehicular Targeted Drug Delivery
1.
2.
3.
4. Surgery • Surgical excision of cancer tissues • Accompany pain, risk of infection, poor wound healing Radiation • Method of completely killing cancer cells or shrinking tumors or relieving symptoms using high-energy radiation • Harm health tissues and damage nearby normal cells • Accompany pain, nausea, hair loss, damage to normal cells Chemotherapy • Chemical method of killing cells that divide rapidly (cancer cells) • Kills normal cells that divide rapidly under normal conditions • Accompany pain, nausea, memory loss, malnutrition
5. Target to tumor cell Signaling Agent Targeting Agent Monitor targeting Drug Smuggle attached drug into tumor cell Released inside tumor cell Targeted Drug Delivery Systems • Nano-particle that carries attached drug to the site of action, with its path monitored by attached fluorescent detecting agent Tumor Cell Blood stream Technical Advantages • Higher efficacy resulting from selectively targeting and killing cancer cells • Reduced toxicity and lower side-effects • Potentially more cost-effective • Prospect for shorter treatments times
6. Dendrimers : Ideal Building Block for Creating a Biologically Active Nano-material Dendrimers : Repeatedly Branched Molecules • Consist of a series of chemical shells built on a small core molecule • Each shell (generation) consists of monomer layers, made by repeating chemical-linking • Beyond G5 : Begin to become spherical and 3-D structure
7. Surface Groups • Can be variously functionalized • Cationic / Anionic / Neutral • Targeting groups • Dyes & Biomarkers Similarity to Protein • Size / Weight • Very well-defined chemical structure • Ease of cellular uptake
8. Targets : Folic Acid (FA) • FAR (high affinity receptor for FA) : over-expressed in several human cancers, even up to a 100-fold • Easily available and inexpensive / small molecular size Therapeutic Agent : Methotrexate (MTX) • Widely used chemotherapeutic drug for the treatment of a variety of malignancies • Inhibits cytosolic enzyme dihydrofolatereductase (DHFR) • Results in depletion of reduced FA required for nucleotide synthesis • Thus leading to the inhibition of DNA replicationand subsequent cell death Fluorescence Tag • Various chemicals : Fluorescein, AlexaFluor • Used for monitoring and tracking
9. Fluorescent tagged nanodevice are taken up through the receptors then spread into cytosolic area To Target Specifically to Cancer Cells • Cells have on their surfaces receptors for specific molecules • Specific receptors for specific molecules are targeted • Specificity can be precisely controlled by targeting active receptor • Taken up into the cell through specific receptor on cancer cell
10. Difficult to Assemble Multiple Functions onto One Dendrimer • Complex chemistry needed for self-assembly of core and shell dendrimers • No specificity between the coupling of dendrimers Self-Assembly using DNA • Each of two dendrimers carries single-stranded DNA with the same length • DNA strands are complementary • Self-assembly with forming double-stranded DNA • Barbell-shaped, two-dendrimer complexes • Fluorescence can be separated to the other
11. Preparation of Each DNA-Dendrimer Conjugate 1. Control surface charge density of amines - By substituting with acetyl groups to prevent infinite network formation due to electrostatic interaction - Acetylation limited to 90% of amines due to densely packed structure - G5 : 12 amine groups / G7 : 108 amine groups 2. Prepare DNA strand - 16-32 nucleotides for spacer from dendrimer / 34 for complementary base pairing 3. EDC/imidazole (0.1M) chemistry used : to activate DNAs for 10mins 4. Slowly mix with LiCl (0.5M) used to weaken electrostatic interactions 5. Allow to react overnight at RT 6. Remove small molecules with membrane filter 7. Purify non-conjugated DNA from using gel electrophoresis 8. Extract purified DNA-dendrimer conjugate from gel 9. Each dendrimer is functionalized : Target, drug and Fluorescence
12. G5 G5 G7 G7 Annealing Self-assembly 1. Mix two DNA-conjugated G7 and G5 dendrimers in equimolar ratio - to prevent crosslinking and formation of very large complexes 2. Annealing : Heated at 90°C for 10 mins with hybridization buffer 3. Cool at RT for 3 hours