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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.
Intro
Functional biological assemblies are inspiration for nanotechnological systems and devices Molecular recognition btw. building blocks self-assembly formation of functional devices motors, pumps, cables, etc, all functioning at the nano-scale
Bionano-DNA as template
Gazid E., FEBS Journal, 2006
DNA is very suitable for nanotechnological applications from the material science point of view:
1.
2. 3. 4.
Bionano-DNA as template
Gazid 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)
Inspired by Nature-1
Yusko, E.C et. al, Nature Nanotechnology, 6:253260, 2011
Challenges to reach the full potential of nanopore-based sensing: reliable fabrication 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 walls and 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
Inspired by Nature-2
Yusko, E.C et. al, Nature Nanotechnology, 6:253260, 2011
Fig 1: Insects detect pheromones by translocating odorant molecules through lipid-coated nanopores (D: 665 nm) Fig 2: Lipid coatings are thought to participate in the capture, preconcentration 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
Inspired by Nature-3
Yusko, E.C et. al, Nature Nanotechnology, 6:253260, 2011
Clogging Problem: Amyloidogenic peptides: e.g. Alzheimer's disease-related amyloid-beta (A) peptides
Self-Assembly of a Viral Molecular Machine from Purified Protein and RNA Constituents
Poranen et al, Molecular Cell, Vol. 7, 845854, 2001
Cellular imaging
in Cell
Cell tracking: Different population of cells in tissue
in Cell
in Cell
Photo-thermal therapy
in Cell
MRI and Cell Tracking Fate of cells in the implanted area Anticancer therapy
in Cell
Nanoscale materials can be used as drug delivery vehicles to develop highly selective and effective therapeutic and diagnostic systems Nano vs micro
nanoscale particles can travel through the blood stream without sedimentation or blockage of the microvasculature Small nanoparticles can circulate in the body and penetrate tissues nanoparticles can be taken up by the cells through natural means such as endocytosis
Modifications: Nonadhesive surface coatings Attachment of molecules for targetting Layer-by-layer methods: shown to regulate nanoparticle biodistribution: cationic pegylated liposomes are preferantially uptaken by the liver and tumor vessels in stead of spleen and blood accumulation Synthesis from amphiphilic polymers
Nano-Layered Microneedles for Transcutaneous Delivery of Polymer Nanoparticles and Plasmid DNA
DeMuth et al, 2010, Advanced Materials
A) B) C) D)
Nanoparticles for ex vivo siRNA delivery to dendritic cells for cancer vaccines: Programmed endosomal escape and dissociation
Akita et al (2010) and Kogure et al (2007) J. Cont. Rel
Targeted PLGA nano- but not microparticles specifically deliver antigen to human dendritic cells via DC-SIGN in vitro
Cruz et al (2010), J. Cont. Rel.
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
Nanotech in Bio-Sensing
Cationic nanoparticles formed by the conjugation of cholesterol and antimicrobial peptides (AMPs): to cross the bloodbrain barrier for treatment of fatal Cryptococcal (Wang et al. Biomaterials 31(10):2874 2881 2010) Nanostructured thin films with immobilized AMPs as an agent intended to combat and prevent infection and formation of Staphylococcus biofilm related implant failure (Shukla et al. Biomaterials 31(8):23482357, 2009)
Interface: NSA-1
1. Park, S; Hamad-Schifferli, K, Current Opinion in Chemical Biology, 14: 616622, 2010 2. You, et al, Nano Today 2 (2007), 3443 3. Park and K. Hamad-Schifferli, ACS Nano 4 (2010), 25552560
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
Interface: NSA-2
Utilizing NSA: (a) Tunable intracellular release from NPDNA nanoplexes (b) Enhancing protein translation: In vitro gene expression with DNA, AuNP recruits mRNA and translation related molecules into its proximity (c) Protein coronas induce a biological response
Nanonetworks
Communication???
Nanomechanical Acoustical Electromagnetic Chemical or Molecular Short-range: Molecular motors Ca2+ signalling Long-range: Pheromones