Innovation and Development of Study Field. nano.tul.cz

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1 Innovation and Development of Study Field Nanomaterials at the Technical University of Liberec nano.tul.cz These materials have been developed within the ESF project: Innovation and development of study field Nanomaterials at the Technical University of Liberec

2 Technical University of Liberec Nanomaterials in therapy, analysis and diagnosis 2

3 Outlook Diagnostics Nanomaterials in analytical atomic spectroscopy Therapy Theranostics Cancer treatment 3

4 Diagnostics - nanoimaging Illustration for applications of inorganic nanomaterials in various imaging modalities. CT denotes computed tomography, MRI magnetic resonance imaging, PET positron emission tomography, SPECT single photon emission computed tomography, GN goldnanocage, QDs quantum dot, QRs, quantum rod, CNTs carbon nanotubes, MSN mesoporous silica nanoparticles, and Au gold nanoparticles. 4 F. Yang et al. / Cancer Treatment Reviews 38 (2012)

Diagnostics - nanoimaging Magnetic nanoparticles have become important tools for the imaging of prevalent diseases, such as cancer, atherosclerosis, diabetes, and others.

5 Diagnostics - nanoimaging Magnetic nanoparticles have become important tools for the imaging of prevalent diseases, such as cancer, atherosclerosis, diabetes, and others. While first generation nanoparticles were fairly nonspecific, newer generations have been targeted to specific cell types and molecular targets via affinity ligands. PC3 (red histogram) cells were incubated with the HPN peptide or HPN peptide labelled nanoparticles (green histogram) then analysed via flow cytometry. 5 In vivo imaging of prostate cancer

Diagnostics - nanoimaging The most common methods of diagnostics are based on fluorescent microscopy that in non-destructive manner monitors labeled nanoparticles in the body of a patient in real

6 Diagnostics - nanoimaging The most common methods of diagnostics are based on fluorescent microscopy that in non-destructive manner monitors labeled nanoparticles in the body of a patient in real time, thereby providing information about the spatial distribution of the test compound in different cell compartments. Fluorescent microscopy of HTC116 (human colorectal tumour) 6

Diagnostics - microchips DNA chips are commonly used in the analysis of DNA and RNA. Their function is based on the hybridization of oligonucleotide probes.

7 Diagnostics - microchips DNA chips are commonly used in the analysis of DNA and RNA. Their function is based on the hybridization of oligonucleotide probes. Matrix containing DNA microarrays, which are spread over different oligonucleotides, may detect simultaneously different DNA sequences. 7 DNA microchip

8 Diagnostics - microchips For protein microarrays the detection is conducted with use of radioactive, fluorescent or electrochemically labelled probes, Probe molecules, typically labelled with a special dye, are added to the array. Any reaction between the probe and the immobilised protein emits a fluorescent signal that is read by a laser scanner, Protein microarrays are rapid, automated, economical, and highly sensitive, consuming small quantities of samples and reagents. The high-throughput technology behind the protein microarray was relatively easy to develop since it is based on the previously developed DNA microarray technology. 8

$Fijalkowski et al. Thick diamond layers for biomedical applications, Sufrace and Coatings Technology A. Karczemska et al.$

9 Diagnostics - microfluidics A very high thermal conductivity coefficient gives a possibility of very efficient dissipation of Joule heat from the diamond electrophoretic microchip. This enables manufacturing of a new generation of microdevices. Joule heat for diamond microfluidic device Joule heat for glass microfluidic device Diamond microfluidic device 9 M. Fijalkowski et al. Thick diamond layers for biomedical applications, Sufrace and Coatings Technology A. Karczemska et al. Materials Science and Engineering B, 176 (2011) 326

10 Diagnostics MRI (magnetic resonance imaging) Super paramagnetic iron oxide (SPIO) nanoparticles are used to enhance the contrast of MRI. MRI labelling can be done by attaching the nanoparticles to the stem cell surface or causing uptake of the particle by the stem cell through endocytosis or phagocytosis. Cells labelled with nanoparticles 10

11 Diagnostics dextran Dextran is polysaccharide composed of glucose units. Besides the fact that can be delivered directly to specific tissues dextrans may also protects against phagocytosis and prolong residence of nanoparticles in the blood. Dextran has long been used as a temporary plasma substitute because of its excellent biocompatibility. Dextran

These micelles can encapsulate multiple superparamagnetic iron oxide nanoparticles and form nanostructures in

12 Diagnostics MRI (magnetic resonance imaging) Modified starlike dextran can self-assemble into nanoscale micelles in water. These micelles can encapsulate multiple superparamagnetic iron oxide nanoparticles and form nanostructures in water. Resulting nanocomposite have a high relaxivity under a clinical magnetic resonance imaging (MRI) scanner. dextran wrapped superparamagnetic iron oxide nanoparticle 12

13 Nanomaterials in analytical atomic spectroscopy Nanomaterials have attracted considerable interest in analytical chemistry (e.g., sample pre-concentration, molecular probes, and biological and electrochemical sensing). Applications of nanomaterials in analytical atomic spectrometry involves: Improvement of the sensitivity and the selectivity, broadening the application range to biological-molecule detection, characterization and determination of nanomaterials themselves 13 X. Jiang et al. Trends in Analytical Chemistry, Vol. 39, 2012

14 Nanomaterials in analytical atomic spectroscopy Analysis of white light by dispersing it with a prism is an example of spectroscopy 14 X. Jiang et al. Trends in Analytical Chemistry, Vol. 39, 2012 Nanomaterials in analytical atomic spectrometry.

Nanomaterials in analytical atomic spectroscopy On-line, simple and automated inorganic chromium-speciation-analysis method using flow-injection nano-tio2 minicolumn separation and electrothermal

15 Nanomaterials in analytical atomic spectroscopy On-line, simple and automated inorganic chromium-speciation-analysis method using flow-injection nano-tio2 minicolumn separation and electrothermal atomic absorption spectrometric detection. Without any additional oxidizing / reducing process, Cr(VI) or Cr(III) species, were respectively, mixed with HCl or NH 3 *H 2 O solutions and passed through the minicolumn where the chromium species were selectively preconcentrated and separated. 15 X. Jiang et al. Trends in Analytical Chemistry, Vol. 39, 2012 P. Wu, H. Chen, G. Cheng, X. Hou, J. Anal. At. Spectrom. 24 (2009) 1098.

16 Nanomaterials in analytical atomic spectroscopy 16 The determination of selenium by atomic fluorescence spectrometry using nano-tio2. D.Y. Deng, J.R. Zhou, X. Ai, L. Yang, X.D. Hou, C.B. Zheng, J. Anal. At. Spectrom. 27 (2012) 270

Therapy drug delivery Nanoparticles can be used in therapy as an active agents, or as drug carriers Nanoparticles based drug transport has many advantages: Protection of drugs

17 Therapy drug delivery Nanoparticles can be used in therapy as an active agents, or as drug carriers Nanoparticles based drug transport has many advantages: Protection of drugs and other biologically active substances from degradation in the body Increased stability of medical substances Greater control over the distribution of substances in the organism 17

18 Therapy drug delivery Drug delivery nanoparticle systems 18 E. Panzarini et al. Cancers 5 (2013)

19 Therapy - neurosurgery Peripheral nerve regeneration remains a significant clinical challenge to researchers. Progress in the design of tissue engineering scaffolds provides an alternative approach for neural regeneration. Nanofiber nonwoven materials can serve as carriers of stem cells for bridging spinal cord lesions. Nanofibrous scaffolds fabricated by electrospinning methods and then reeled into aligned nerve guidance conduits can promote nerve regeneration natural synthetic polyblend nanofibers for peripheral nerve regeneration

Therapy - neurosurgery Bridges implanted into the injured spinal cord function to stabilize the injury, while also supporting and directing axon growth.

20 Therapy - neurosurgery Bridges implanted into the injured spinal cord function to stabilize the injury, while also supporting and directing axon growth. The architecture of the bridge is critical to its function, with pores to support cell infiltration that integrates the implant with the host and channels to direct axon elongation. Degradable poly(lactide-co-glycolide) multiple channel bridges for implantation into a lateral hemisection 20

Cancer treatment Inorganic nanoparticles for pancreatic cancer research. Green solid lines represent that pancreatic cancer clinical studies have been applied.

21 Cancer treatment Inorganic nanoparticles for pancreatic cancer research. Green solid lines represent that pancreatic cancer clinical studies have been applied. Green dotted lines indicate experimental studies in pancreatic cancer. Red lines represent no pancreatic cancer research, but researches in other cancers. 21 F. Yang et al. / Cancer Treatment Reviews 38 (2012)

22 Cancer treatment photodynamic therapy Photodynamic cancer therapy is based on the destruction of the cancer cells by laser generated atomic oxygen, which is cytotoxic. A greater quantity of a special dye that is used to generate the atomic oxygen is taken in by the cancer cells when compared with a healthy tissue. Hence, only the cancer cells are destroyed then exposed to a laser radiation. 22 OV. Salata, Journal of Nanobiotechnology 2004, 2:3

Cancer treatment photodynamic therapy Graphene oxide (GO), graphene s water-soluble derivative, has been found important potential applications in drug delivery and enzyme

Properly functionalized graphene oxide may also act as drug delivery system for targeted photodynamic therapy.

23 Cancer treatment photodynamic therapy Graphene oxide (GO), graphene s water-soluble derivative, has been found important potential applications in drug delivery and enzyme immobilization due to their large specific surface area and abundant functional groups (epox-ide, hydroxyl, and carboxylic groups). Properly functionalized graphene oxide may also act as drug delivery system for targeted photodynamic therapy. Photosensitizers Ce6 loaded by folic acid-conjugated graphene oxide. 23 Huang P, Xu C, Lin J, Wang C, Wang X, Zhang C, Zhou X, Guo S, Cui D. Folic Acid-conjugated Graphene Oxide loaded with Photosensitizers for Targeting Photodynamic Therapy. Theranostics 2011; 1:

Cancer treatment photodynamic therapy The nanocarrier-encapsulated PSs (photosensitizer) accumulate in the tumour tissue by the enhanced permeability and retention (EPR) effect.

24 Cancer treatment photodynamic therapy The nanocarrier-encapsulated PSs (photosensitizer) accumulate in the tumour tissue by the enhanced permeability and retention (EPR) effect. Upon photoirradiation, reactive oxygen species (ROS) generated from PSs can directly kill tumour cells. PDT can also cause vascular collapse and embolization, leading to tumour destruction through a lack of oxygen and nutrients. 24

25 Cancer treatment - photothermal therapy (PTT) During the local heating or hyperthermia, cells undergo irreversible damage due to the denaturation of proteins and the disruption of the cell membrane. But these thermal treatments damage the healthy tissues as well. More recently, incorporation of laser radiation treatment in thermal cancer therapy opened up a photothermal therapy method for the selective treatment of cancers. Application of nanoparticles helps the selective heating at the local environment. Basic requirements of PTT are a biocompatible PT agent with large absorption coefficient in the NIR regions and an NIR light source. Thus, surface-modified nanomaterials of carbon, metals, and semiconductors with NIR absorption can be ideal PT agents. 25 E.S. Shibu et al. / Journal of Photochemistry and Photobiology C: Photochemistry Reviews 15 (2013) 53 72

26 Cancer treatment - photothermal therapy (PTT) Various plasmonic nanostructures with absorption in the NIR region. (A) Au nanorods, (B and C) Ag nanocubes, (D) Au mesoflowers, (E) Au nanooctahedra, (F) Au nanoframes, (G) Au nanocages, (H) Au Ag nanoboxes, (I) Au nanostars, (J, K) Ag/Au nanotubes, (L) silica Au core shell NPs, (M) Ag nanotriangles, (N) single walled carbon nanotube (SWCNT), and (O) graphene oxide. 26 E.S. Shibu et al. / Journal of Photochemistry and Photobiology C: Photochemistry Reviews 15 (2013) 53 72

27 Cancer treatment - theranostics The ability of nanoparticles to both diagnose and treat diseases is an emerging concept. Theranostics is: the coupling of diagnostics and therapeutics the ability to find, diagnose and treat at the same time Image of cancer cells after incubation with gold NPs showing their membrane coupling 27 Lapotko, D. Plasmonic Nanobubbles as Tunable Cellular Probes for Cancer Theranostics. Cancers 2011, 3,

Theranostics - the rise of targeted magnetic nanoparticles Unlike that found in normal tissue, tumour vasculature is leaky owing to fenestrations and gaps between endothelial cells that result from

28 Theranostics - the rise of targeted magnetic nanoparticles Unlike that found in normal tissue, tumour vasculature is leaky owing to fenestrations and gaps between endothelial cells that result from abnormal angiogenesis. MNPs in circulation can passively extravasate through these gaps and enter the tumour interstitium. Poor lymphatic drainage found in some tissues helps to retain particles in the tumour space. 28

Theranostics - the rise of targeted magnetic nanoparticles Targeted MNPs delivered to the tumour are exposed to an alternating current magnetic field, which causes the nanoparticles to absorb energy

29 Theranostics - the rise of targeted magnetic nanoparticles Targeted MNPs delivered to the tumour are exposed to an alternating current magnetic field, which causes the nanoparticles to absorb energy by increasing their alignment (lower entropy state) with the applied field. This energy is then converted to heat when the particles undergo relaxation. Tumours possess thermal hypersensitivity compared to normal tissues when heated to temp. ranging from 41 C to 47 C. Concern regarding overheating of normal tissues remains, however, and represents an important limitation to this method. 29

Theranostics - monitoring of therapeutic efficacy Imaging and treatment or brain tumours, based upon the encapsulation of iron oxide nanoparticles and the photosensitizer Photofrin within PEGylated

30 Theranostics - monitoring of therapeutic efficacy Imaging and treatment or brain tumours, based upon the encapsulation of iron oxide nanoparticles and the photosensitizer Photofrin within PEGylated amine functionalized polyacrylamide nanoparticles. Monitoring of therapeutic efficacy using multifunctional nanoparticles in brain tumors. T2-weighted magnetic resonance images at day 8 after treatment from (A - C) a representative control and tumors treated with (D) laser light only, (E) administration of Photofrin plus laser light, and (F) nontargeted nanoparticles containing Photofrin plus laser light 30

31 Vision of future The major trend in further development of nanomaterials is to make them multifunctional and controllable by external signals or by local environment thus essentially turning them into nano-devices. During 15 to 20 years it is expected the introduction of entirely new equipment, based on nanotechnology, into medical and pharmaceutical applications. 31

Vision of future Nanorobots intended for destruction of microbial pathogenes Respirocyte that uses blood glucose as the source of energy moves 236 times more oxygen than natural blood cell.

32 Vision of future Nanorobots intended for destruction of microbial pathogenes Respirocyte that uses blood glucose as the source of energy moves 236 times more oxygen than natural blood cell. They could be used for the transfusion of blood substitutes, treatment of anaemia, pulmonary disease, facilitate the cardiovascular and neurovascular therapeutic interventions Possibility of separation of harmful substances from the blood 32

33 Vision of future New nano-structured materials as targeted delivery of drugs or encapsulating anticancer drugs. Analysis of urine, blood and other body fluids using nanoparticles. Fluorescent nanoparticles in detection technologies (analysis of infectious and genetic diseases, pharmaceutical research). Separation of DNA fragments (rapid sequencing), sensors for pharmacogenetics, Obtaining information on the structure of different tissues through nanomachines 33

Ciência (Bio)nanosystems based on quantum dots, plasmonic or magnetic nanoparticles

Ciência (Bio)nanosystems based on quantum dots, plasmonic or magnetic nanoparticles Ciência 216 (Bio)nanosystems based on quantum dots, plasmonic or magnetic nanoparticles Paulo J. G. Coutinho Departamento/Centro de Física Escola de Ciências Universidade do Minho 4 Julho 216 OVERVIEW