See references below for related reading.
2.1 Elements of good engineering design
2.1.1 Whenever possible, use a general design that has already been tested
2.1.2 Whenever possible, take advantage of “biomimicry” – Nature has tried many designs!
2.1.3 Avoid “general purpose” design. Use multiple specific molecules to do specific tasks.
2.1.4 Control the order of molecular assembly to control the order of events
2.1.5 Therefore, perform the nano assembly in reverse order to the desired order of events
2.2 Building a nanodevice
2.2.1 Choice of core materials
2.2.2 Add drug or therapeutic gene
2.2.3 Add molecular biosensors to control drug/gene delivery
2.2.4 Add intracellular targeting molecules
2.2.5 Result is multi-component, multi-functional nanomedical device
2.2.6 For use, design to de-layer, one layer at a time
2.2.7 The multi-step drug/gene delivery process in nanomedical systems
2.3 The challenge of drug/gene dosing to single cells
2.3.1 Precise targeting of drug delivery system while protecting non-targeted cells from exposure to the drug
2.3.2 How to minimize mis-targeting
2.3.3 How to deliver the right dose per cell
2.3.4 One possible solution – in situ manufacture of therapeutic genes
2.4 Bridging the gap between diagnostics and therapeutics
2.4.1 how conventional medicine is practiced in terms of diagnostics and therapeutics
2.4.2 the consequences of separating diagnostics and therapeutics
2.4.3 a new approach – "theragnostics" (or "theranostics")
2.5 Examples of current theragnostic systems
2.5.1 example 1: Rituxan ("Rituximab)(an example of not using diagnostics to guide the therapy)
2.5.2 example 2: Herceptin ("terastuzumab")
2.5.3 example 3: Iressa ("Gefitinib)
2.5.4 other examples
2.6 How theragnostics relates to Molecular Imaging
2.6.1 conventional imaging is not very specific
2.6.2 types of In-vivo Imaging
22.214.171.124 X-rays, CAT (Computed Axial Tomography) scans
126.96.36.199 MRI (magnetic Resonance Imaging)
188.8.131.52 PET (Positron Emission Tomography) scans
2.6.3 "molecular imaging" of nanoparticles in-vivo for diagnostics/monitoring of therapeutics
2.8 Engineering nanomedical systems for simultaneous molecular imaging
2.8.1 using nanomedical cores for MRI contrast agents
2.8.2 difficulties in using PET probes for nanomedical devices
2.8.3 using cell-specific probes for molecular imaging of nanomedical devices
2.8.4 breaking the "diffraction limit" – new nano-level imaging modalities
2.9 Theragnostic nanomedical devices
2.9.1 using nanomedical devices to guide separate therapeutic device
2.9.2 when might we want to combine diagnostics and therapeutics?
- Ahn, C. “Pharmacogenomics in Drug Discovery and Development”. Genomics & Informatics Vol. 5(2) 41-45, (2007). (Full text found at genominfo.org)
- McCarthy, J.R., Jaffer,F.A., Weissleder, R. “A Macrophage-Targeted Theranostic Nanoparticle for Biomedical Applications”. Small 2(8-9): 983 – 987 (2006).
- Pan, D., Caruthers, S.D., Hu, G., Senpan, A., Scott, M.J., Gaffney, P.J., Wickline, S.A., Lanza, G.M. “Ligand-Directed Nanobialys as Theranostic Agent for Drug Delivery and Manganese-Based Magnetic Resonance Imaging of Vascular Targets”. J. AM. CHEM. SOC., 130, 9186–9187 (2008) (Full text found at nih.gov)
- Prow, T.W., Rose, W.A., Wang, N., Reece, L.M., Lvov, Y., Leary, J.F. "Biosensor-Controlled Gene Therapy/Drug Delivery with Nanoparticles for Nanomedicine" Proc. of SPIE 5692: 199 – 208, 2005.
Researchers should cite this work as follows:
James Leary (2011), "BME 695L Lecture 2: Designing Nanomedical Systems," http://nanohub.org/resources/11968.
1083 BME, Purdue University, West Lafayette, IN