BME 695L Lecture 8: Surface Chemistry: attaching nanomedical structures to the core

See references below for related reading.8.1      Introduction8.1.1    attachment strategies typically depend on core composition8.1.2    but the attachment strategy should not drive the core choice8.1.3    the choice of core should still depend on the desired overall “multifunctional” nanomedical device8.2      “Surface chemistry” strategies for attachment of biomolecules to the core material8.2.1    hydrophobic versus hydrophilic core materials8.2.2    addition of biomolecules for biocompatibility8.2.3    monofunctional versus bifunctional surface chemistry strategies8.2.4    PEGylation as “stealth strategy” to minimize opsonification and increase circulation time8.2.5    pay attention to overall zeta potential during the surface chemistry process!8.3      Two main attachment strategies8.3.1    covalent bonding strategies         8.3.1.1 advantages             8.3.1.1.2 very stable             8.3.1.1.3 can control process of bond disruption for multilayering         8.3.1.2 Disadvantages             8.3.1.2.1 can be too stable and difficult to disassemble             8.3.1.2.2 must be careful to avoid or minimize use of strong organic solvents that can be cytotoxic even at trace concentrations8.3.2    non-covalent (primarily electrostatic) Bonding Strategies         8.3.2.1 advantages             8.3.2.1.1 can use very gentle chemistries for biocompatibility             8.3.2.1.2 chemistry can be very simple layer-by-layer assemblies             8.3.2.1.3 easier to disassemble multilayered structures         8.3.2.2 disadvantages             8.3.2.2.1 instability - different pH and ionic strength environments can cause layers to spontaneously disassemble at undesired times             8.3.2.2.2 zeta potential can suddenly change as layers spontaneously strip off8.4      Special considerations for the final attachment design8.4.1    preparing the nanoparticle for addition of targeting and therapeutic molecules8.4.2    what are the special requirements, if any, for these molecules?         8.4.2.1 how to attach without changing function of molecule         8.4.2.2 does this molecule need to stay attached, or not, to the nanoparticle in order to function8.4.3    testing for targeting and therapeutic efficacy at the single cell level8.5      Attaching different types of targeting molecules (some types and examples)8.5.1    antibodies – which end to attach?8.5.2    peptides – which end to attach, steric hindrance? Spacer arm needed?8.5.3    aptamers - which end to attach, steric hindrance? Spacer arm needed?8.5.4    small molecule ligands - which end to attach, steric hindrance? Spacer arm needed?8.6      Testing the nanoparticle-targeting complex8.6.1    ways of detecting this complex8.6.2    ways of assessing targeting/mistargeting efficiency and costs of mistargeting8.6.3    is the nanoparticle still attached to the targeting molecule?8.7      Attaching/tethering different types of therapeutic molecules8.7.1    antibody therapeutics - need to interact with the immune system to activate8.7.2    peptides (e.g. apoptosis-inducing peptides)8.7.3    therapeutic aptamers8.7.4    transcribable sequences8.7.5    small drugs 8.8      Testing the nanoparticle-therapeutic molecule complex8.8.1    direct and indirect ways of detecting the therapeutic molecules8.8.2    ways of assessing the therapeutic efficacy at single cell level8.8.3    is the nanoparticle still attached to the therapeutic molecule? Is that important?8.9      Nanomedical pharmacodynamics – the great unknown8.9.1    little is known about complex nanoparticle pharmacodynamics8.9.2    obtaining quantitative biodistribution data is extremely difficult!8.9.3    some possible new approaches