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nanobiotechnology & bionanotechnology

nanobiotechnology & bionanotechnology. Intro. Two of m ost promising technologies of future: Biotechnology : Use of living in the creation of wealth (products or processes)

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nanobiotechnology & bionanotechnology

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  1. nanobiotechnology& bionanotechnology

  2. Intro • Two of most promising technologies of future: • Biotechnology: Use of living in the creation of wealth (products or processes) • Nanotechnology: creation, investigation and utilisation of systems that are 1000 times smaller than the components currently used in the field of microelectronics. • The interface of these two worlds lies Nanobiotechnology • It uses nanotechnology to analyse and create biological nanosystems • It uses biological materials and structural plans to produce technical, functional nanosystems

  3. Intro • Functionalbiological assemblies are inspiration for nanotechnologicalsystems and devices • Molecularrecognition btw.building blocksself-assemblyformation offunctional devices • motors,pumps, cables, etc, all functioning at the nano-scale

  4. What we should know and what are the possibilities?? • Interaction between biological and non-biological devices??? • Interactions with biological as well as non-biological substrates • Toxicity • How does nature make use of adhesive and anti-adhesive interactions? • Screening methods in biology • Bio-Chips • Lab-on-a-chip • Nanotechnologicallymodified biomaterials • Nano aspects of biological systems • Nanotechnological tools to improve biomaterials • Nanoparticles as therapeutic drug carriers and diagnostics • Drug, oligonucleotide, imaging agents • Nanodevicesin medicine, pharmacy and biology

  5. Bionano-DNA as templateGazid E., FEBS Journal, 2006 DNA is very suitable for nanotechnologicalapplications from the material sciencepoint of view: • The diameter of ssDNA is less than1 nm • DNA molecules are chemically very robust • Lowcost of large-scale chemicalDNA synthesis • Easy modification: for example, bybiotinylationor thiolation

  6. Bionano-DNA as templateGazid E., FEBS Journal, 2006 Examples: • DNA used in the formation of nanowires (1998):Metallization of dsDNA btw two gold electrodes to form conductive silver nanowire • DNA-binding proteins (Figure)

  7. DNA Codes for Nanoscience Holliday junction Assembly of gold nanoparticles Immobilization of gold NP PCR mediated introduction of new fuctionalities to create DNA-protein hybrids Self-replication of connectivity

  8. Inspired by Nature-1Yusko, E.C et. al, Nature Nanotechnology, 6:253–260, 2011 Challenges to reach the full potential of nanopore-based sensing: • reliablefabrication of synthetic nanopores on the sub-nanometre scale • better control of translocation times of single-molecule analytes • methods to control the surface chemistry inside synthetic pores: reduce non-specific interactions of analytes with the pore wallsand prevent pore clogging • low frequency of translocation events at low analyte concentrations and the poor specificity of the nanopores for analytes need to be improved

  9. Inspired by Nature-2Yusko, E.C et. al, Nature Nanotechnology, 6:253–260, 2011 Fig 1: Insects detect pheromones by translocating odorant molecules through lipid-coated nanopores (D: 6–65 nm) Fig 2: Lipid coatings are thought to participate in the capture, pre-concentration and subsequent translocation of odorants to specific receptors Fig 3: Capture, affinity-dependent pre-concentration and translocation of specific proteins after binding to ligands on mobile lipid anchors

  10. Inspired by Nature-3Yusko, E.C et. al, Nature Nanotechnology, 6:253–260, 2011 • Clogging Problem: Amyloidogenic peptides: e.g. Alzheimer's disease-related amyloid-beta (Aβ) peptides

  11. Self-Assembly of a Viral Molecular Machinefrom Purified Protein and RNA ConstituentsPoranen et al, Molecular Cell, Vol. 7, 845–854, 2001 • Understanding of self-assembly in nature…

  12. Cellular imaging

  13. in Cell Cell tracking: Different population of cells in tissue

  14. in Cell

  15. in Cell Photo-thermal therapy

  16. in Cell Anticancer therapy MRI and Cell Tracking • Fate of cells in the implanted area

  17. in Cell

  18. Nanotech in Drug Delivery • Controlled drug-delivery systems deliver drugs in the optimum dosagefor long periods • increasing the efficacy of the drug • maximizing patient comfort • enhancing the abilityto use highly toxic, poorly soluble or relatively unstabledrugs • Nanoscale materials can be used as drugdelivery vehicles to develop highly selective and effectivetherapeutic and diagnostic systems • Nano vs micro • nanoscale particles can travel through the blood stream without sedimentationor blockage of the microvasculature • Smallnanoparticles can circulate in the body and penetrate tissues • nanoparticles can betaken up by the cells through natural means such asendocytosis

  19. Nanotech in Drug Delivery • Particle Size, Surface-to-Volume Ratio, Surface Area, andSurface Free Energy • Biological Reactivity • Opsonisation: thought to be thegreatest threat engulfment of foreign particles injected into the bloodstream by specific macrophages cells of RES (reticulo endothelial system) Modifications: • Nonadhesive surface coatings • Attachment of molecules for targetting • Layer-by-layer methods: shown to regulatenanoparticle biodistribution: cationic pegylated liposomes are preferantially uptaken by the liver and tumor vessels in stead of spleen and bloodaccumulation • Synthesis from amphiphilic polymers

  20. Nano-Layered Microneedles for Transcutaneous Delivery of Polymer Nanoparticles and Plasmid DNA DeMuth et al, 2010, Advanced Materials Luciferase gene and lipid-coated PLGA NPs were delivered seperately. • SEM micrograph of uncoated PLGA microneedle arrays • Polyelectrolyte layers • 24 bilayers for 5 min • 1 bilayer for 24 h • 5 bilayers for 24 h • 24 bilayers for 24 h

  21. Nanoparticles for ex vivo siRNA delivery to dendritic cells for cancer vaccines: Programmed endosomal escape and dissociationAkita et al (2010) and Kogure et al (2007)J. Cont. Rel Solution?? • Programmed packaging

  22. Targeted PLGA nano- but not microparticles specifically deliver antigen to human dendritic cells via DC-SIGN in vitroCruz et al (2010), J. Cont. Rel. • Specific targeting of NPs to human DCs enhances antigen presentation

  23. Nanotech in Medicine: Oncology • It can complement existing technologies for detection, prevention, diagnosis and treatment • Useful in the area of biomarker research and increase sensitivity in assays with relatively small sample volume Jain, KK, BMC Medicine 2010, 8:83

  24. Nanotech in Tissue Engineering • For proper function and organization, we should mimic native tissuesat the nanoscale • Fabrication: top-down, bottom-up • Modification: Microfabrication and nanofabrication to modify surface properties with resolutionsas small as 50 nm control of cell behavior, orienting cells and guiding cell migration, differentiation??

  25. Cell interactions with hierarchically structured nano-patterned adhesive surfacesArnold, M, et al, Soft Matter, 2009, 5, 72 • Counting the number of clustering cell adhesion based transmembrane proteins is performed by molecular defined, biofunctionalised nanopatterns of defined single protein binding sites confined in micrometre large areas, i.e. hierarchically organised micro-nanopattern

  26. Nanotech in Bio-Sensing

  27. Nanotech in Medicine: AMPs Review: Calderon et al, Amino Acids (2011) 40:29–49 • Cationic nanoparticlesformed by the conjugation of cholesterol and antimicrobial peptides (AMPs): to cross the blood–brain barrier for treatment of fatalCryptococcal(Wang et al. Biomaterials31(10):2874–2881 2010) • Nanostructured thin films withimmobilized AMPs as an agent intended to combat andprevent infection and formation of Staphylococcus biofilmrelated implant failure (Shuklaet al. Biomaterials31(8):2348–2357, 2009)

  28. Interface: NSA-1 • Park, S; Hamad-Schifferli, K, Current Opinion in Chemical Biology, 14: 616-622, 2010 • You, et al, Nano Today 2 (2007), 34–43 • Park and K. Hamad-Schifferli, ACS Nano 4 (2010), 2555–2560 • The biological behavior of nanomaterials depends primarily on how they interface to biomolecules and their surroundings • Issues like non-specific adsorption (NSA) are still the biggest obstacles and have held back widespread practical use of nanotechnology in biology

  29. Interface: NSA-2 Utilizing NSA: • Tunable intracellular release from NP–DNA ‘nanoplexes’ • Enhancing protein translation: In vitro gene expression with DNA, AuNP recruits mRNA and translation related molecules into its proximity • Protein coronas induce a biological response

  30. Nanonetworks • Communication??? • Nanomechanical • Acoustical • Electromagnetic • Chemical or Molecular • Short-range: • Molecular motors • Ca2+ signalling • Long-range: • Pheromones

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