Carmel J Caruana, BioMedical Physics, Institute of Health Care, University of Malta
Vladan Bernard Deparment of Biophysics Lf MU
Nanomedical Devices
(a lecture for future)
Lectures on Medical Biophysics
Department of Biophysics, Medical Faculty,
Masaryk University in Brno

Carmel J Caruana, BioMedical Physics, Institute of Health Care, University of Malta
Vladan Bernard Deparment of Biophysics Lf MU
Basics
•Nanomedical devices - definition: biomedical devices at the scale 1 – 100 nm
•Very multidisciplinary issues
•Promise of nanomedical devices (why we develope it?):
–New methods for prevention, diagnosis, therapy
–Daily screening of health (very fast devices for monitoring of patient - Point Of Care – POC -
testing)
–Therapy targeted to the individual patient
•Origin from Greek language : νάνο – „dwarf“
•dynamic evolution

Carmel J Caruana, BioMedical Physics, Institute of Health Care, University of Malta
Vladan Bernard Deparment of Biophysics Lf MU
At the beginning...
•1959 R. Feynman (1918/88) - „There’s plenty room at the bottom“- presentation on meeting of
American Physical Society – show the possibility to deals with material on molecular size.
•
Feynman-lecture
Challenge for $ 1,000 – 1985
(text 1/25,000 smaller in linear scale)

Carmel J Caruana, BioMedical Physics, Institute of Health Care, University of Malta
Vladan Bernard Deparment of Biophysics Lf MU
Pioneer ...
•Norio Taniguchi – University of Tokio – 1974 first use term nanotechnology
taniguchi
"Nano-technology" mainly consists of the processing of separation, consolidation, and deformation
of materials by one atom or one molecule."

Carmel J Caruana, BioMedical Physics, Institute of Health Care, University of Malta
Vladan Bernard Deparment of Biophysics Lf MU
•Company IBM, has invested considerable finance in „nano“ development and commercial exploitation.
ibm
Pioneers company ...
Logo IBM, 1990 (nikl, xenon, SEM)
„A boy and his atom“ 2013
The "smallest film" was created as part of experimental outputs. This was done using a scanning
tunnel microscope. (www.CSFD.cz – 63% :c) )
http://upload.wikimedia.org/wikipedia/en/3/37/A_Boy_and_His_Atom_%28still%29.jpg
http://www.youtube.com/watch?v=oSCX78-8-q0

Carmel J Caruana, BioMedical Physics, Institute of Health Care, University of Malta
Vladan Bernard Deparment of Biophysics Lf MU
IBM and „nanoworld“ ...
IBM - Scanning Tunneling Microscope – how to observe nanoworld
Výsledek obrázku pro IBM scanning microscope
IBM.com

Carmel J Caruana, BioMedical Physics, Institute of Health Care, University of Malta
Vladan Bernard Deparment of Biophysics Lf MU
How much is a nanometer?
Notice much smaller than RBC

Carmel J Caruana, BioMedical Physics, Institute of Health Care, University of Malta
Vladan Bernard Deparment of Biophysics Lf MU
Nano ... in the world, web, science and articles
•Number of references to (articles, books) in ScienceDirect database published in 2011 x 2013 x
2014 x 2015x 2016 x 2017 x 2018 x 2019 x 2020 connected with the phrase:
nano – 151 x 209 x 244 x 262 x 251 x 272 x 313 x 406 x 461 x 528 t
•nanomaterials 23 x 35 x 37 x 47 x 64 x 71 x 85 x 101 x 121 x 147 t
•nanoparticles – 90 x 128 x 135 x 167 x 206 x 227 x 266 x 327 x 378 x 442 t
•brain - 1.148 x 1.286 x 1.378 x 1.419 x 1.380 x1.433 x1.510 x1.612 x1.688 x 1.782 t
•
•Google in 2011, 2012, 2013, 2014, 2015, 2016 x 2017 x 2018 x 2019  :
•
•Nanomaterials – 2.580, 5.230, 4.720, 5.490, 4.990, 5.420, 6.320,15.000,14.300, 40.700 t
•Nanoparticles – 5.670, 12.500 , 11.600, 13.500, 12.800, 14.700, 17.000 , 29.000, 38.200, 35.300
t
•Brain – 264.000, 649.000, 605.000, 557.000,  509.000, 526.000,  652.000 , 958.000, 1240.000,
917.000t

Carmel J Caruana, BioMedical Physics, Institute of Health Care, University of Malta
Vladan Bernard Deparment of Biophysics Lf MU
Definition of nanotechnology
•Focus on the objects smaller than 100 nm (in one diameter)
•Ability to handle and active use these objects and their functions
•The different behavior of nano-technology compared to macro-technology (quantum phenomena, atomic
forces, chemical bonds, ...)
The criteria of nanotechnology
Nanotechnology is the applied science dealing with the production and using of materials and
particles, whose origin is to be targeted at the manipulation of individual atoms or relatively
small groups of atoms.
Nanotechnology (sometimes shortened to "nanotech") is the study of manipulating matter on an atomic
and molecular scale. Generally, nanotechnology deals with developing materials, devices, or other
structures possessing at least one dimension sized from 1 to 100 nanomethers. Quantum mechanical
effects are important at this quantum-realm scale.

Carmel J Caruana, BioMedical Physics, Institute of Health Care, University of Malta
Vladan Bernard Deparment of Biophysics Lf MU
Nanomedicine definition
•is currently inconsistent
•According to the US National Initiative: Nanomedicine is the application of nanotechnology in
medicine •Definitions by Europe Science Foundation is more explicit. It says that "the field of
scope of nanomedicine are science and technology, diagnostic, treatment and prevention of diseases
and injuries leading to pain relief, preserving and improving human health, using tools and
molecular level knowledge of the human body."
Nanomedicine can be generally defined as a comprehensive monitoring, management, repair, protection
and improvement of all human biological systems, operating at the molecular level - and this
purposefully created by using nanodevices and nanostructures, ultimately leading to improved health
status of individuals.

Carmel J Caruana, BioMedical Physics, Institute of Health Care, University of Malta
Vladan Bernard Deparment of Biophysics Lf MU
Categorization of nanomaterials which is used in medicine and "bio-sciences," by D.G. Thomas et al.
/ Journal of Biomedical Informatics 44 (2011) 59–74

Carmel J Caruana, BioMedical Physics, Institute of Health Care, University of Malta
Vladan Bernard Deparment of Biophysics Lf MU
Examples
•… definitely not all existing, only a small percentage of all ...

Carmel J Caruana, BioMedical Physics, Institute of Health Care, University of Malta
Vladan Bernard Deparment of Biophysics Lf MU
Nanoemulsions
•Nanoemulsions are known as dispersion systems consisting of a liquid dispersion medium and liquid
dispersive fraction (inmixible) with the size  of dispersion droplets below 100 nm.
•nanodroplets (usually fats, oils), forming a nanoemulsion system can serve as carriers of drugs or
other substances (e.g. vitamins). Advantages - targeted delivery, increased absorption of the drug
•Preparation of nanoemulsions is done particularly by an ultrasonic field (e.g. by ultrasonic
desintegrator) or "by extrusion" dispersion through the  thin piezoelectric layers with pores
S. Swarnalatha, Nanoemulsion drug delivery by ketene based polyester synthesized using
electron rich carbon/silica composite surface, Colloids and Surfaces B: Biointerfaces 65 (2008)
292–299
20 nm
Many contemporary publications present the possibility of using nanoemulsions as carriers of
anticancer drugs with targeted delivery (subject to the existence of an increased uptake of lipid
droplets in tumor tissue).
 Usability:

Carmel J Caruana, BioMedical Physics, Institute of Health Care, University of Malta
Vladan Bernard Deparment of Biophysics Lf MU
1110-16
Nanoemulsions
Nanoemulsion consisting of: dispersion medium - distilled water, dispersed fraction - lipids and
cholesterol + immunosuppressive agents, emulsifier - alcohol.
N. Vaškovicová, 2010, Department of Biophysics Lf MU
100 nm

Carmel J Caruana, BioMedical Physics, Institute of Health Care, University of Malta
Vladan Bernard Deparment of Biophysics Lf MU
Nanoshell
• A nanoshell is composed of a spherical hollow shell of insulator surrounded by a conducting shell
of a few nanometer in thickness (gold). •By varying the thickness of the conducting shell one can
precisely tune the electric and optical properties of nanoshells e.g., make them absorb a certain
wavelength of light
•
nano1
Computer simulation depicts growth of gold nanoshell: a silica (glass) spherical core covered with
a layer of gold. Gold is a biocompatible compound, making it a useful material for medical
applications.
Courtesy N. Halas

Carmel J Caruana, BioMedical Physics, Institute of Health Care, University of Malta
Vladan Bernard Deparment of Biophysics Lf MU
Nanoshells: Medical Applications -Photothermal Tumor Ablation
•The nanoshells are coated with receptors that bind to tumor cells and are simply injected into the
bloodstream. Once delivered to a tumor, near infrared light is shone through the skin (near IR is
not attenuated much by tissue). The nanoshells absorb the IR and convert it to heat with incredible
efficiency. This raises the temperature of the local environment of the tumor cells by 10-20
degrees and the cells die. Advantage: zero toxic effects (unlike chemotherapy) no ionizing
radiation (like radiotherapy).

Carmel J Caruana, BioMedical Physics, Institute of Health Care, University of Malta
Vladan Bernard Deparment of Biophysics Lf MU
2 3
Nanoshell...
•Thickness of the gold coating determines sensitivity of nanoshells to different wavelengths. The
picture shows the results of theoretical calculations.
Studies with photo thermal ablation of the tumor were performed by a team of researchers Jennifer
West, Houston. The core of the used nanoshell was large 110 nm and  gold coating of thickness 10
nm. By application of nanoshells on the suspension of tumor cells and subsequent laser irradiation
of IR light, temperature increased to 55 ° C and subsequently the viability of the cell suspension
decreasied. Attempts were also done​ with modified nanoshells, whose surface was modified by
antibodies that allow specific binding of nanoshell only to cancer cells anywhere in the body.
Two tumors in the mouse body "saturated"  by specially made "nanoshells" under the influence of
laser light are heated (blue denotes places with higher temperature) and tumor cells die.

Carmel J Caruana, BioMedical Physics, Institute of Health Care, University of Malta
Vladan Bernard Deparment of Biophysics Lf MU
Nanoshells: Medical Applications - Single Molecule Raman Spectroscopy
•Scientists have long known that they could boost the Raman light emissions from a sample by the
addition of colloidal particles to a sample. Nanoshells are colloids and can increase the Raman
signal by 1000 million times. In this way it is possible to characterize single molecules (such as
environmental contaminants, chemical or biological toxins and even viruses). •Advantages: very high
sensitivity, high levels of multiplexing (simultaneous measurement of many biomolecules), ability
to perform detection in blood and other biological matrices.
Sample
Sample +
nanoshells
Raman light emission
Raman light emission
1000 million times increasing

Carmel J Caruana, BioMedical Physics, Institute of Health Care, University of Malta
Vladan Bernard Deparment of Biophysics Lf MU
Nanoshells: Medical Applications - Delivering Insulin – in future???
•Nanoshells loaded with insulin would be injected under the skin, where they would stay for months.
To release the drug, patients would use a pen-sized IR laser over the skin at the injection site.
•
aplication
laser
Heating-release

Carmel J Caruana, BioMedical Physics, Institute of Health Care, University of Malta
Vladan Bernard Deparment of Biophysics Lf MU
http://www.mpibpc.mpg.de/181748/zoom.jpg
DNA nanocage, nanoorigam
•The basis of these structures are two-dimensional "surfaces" formed by chain molecules of DNA.
Another layer of complementary DNA strands can be attached to this matrix thus forming a relief
structure. •The horizontal structure (appropriate combination of complementary DNA strands) can be
"put together" as a cube with an internal cavity (a cage).
1243588966
Relief created by a horizontal structure of the DNA layer height of 2-4 nm (Nick Papadakis,
P.W.K.R)
1243590111
img1243590628
3D model of the structure and its real cryoelectron microscopic image (author of image: Andersen
EC)
One possibility is to use these structures as carriers of drugs and their targeted delivery by
opening of nanocage through enzymatic locks.

Carmel J Caruana, BioMedical Physics, Institute of Health Care, University of Malta
Vladan Bernard Deparment of Biophysics Lf MU
DNA nanocage, nanoorigam
Paul W. K. Rothemund
… when a scientist has a free time …
flat structure consisting of chain molecules of DNA
complementary chain of molecule DNA, formed to „smile“
Map of Americas formed by DNA flat structure
(secundary coloured)

Carmel J Caruana, BioMedical Physics, Institute of Health Care, University of Malta
Vladan Bernard Deparment of Biophysics Lf MU
DNA nanocage
•DNA nanostructures with complex 3D curvatures. (A) Schematic representation of the hemisphere. (B)
Schematic representation of the sphere. (C) Schematic representation of the ellipsoid. (D) TEM
images of the hemisphere, randomly deposited on TEM grids. The concave surface is visible as a dark
area. (E) TEM images of the sphere, randomly deposited on TEM grids. Due to the spherical symmetry,
the orientation can not be determined. (F) TEM images of the ellipsoid. The outline of the
ellipsoid is visible. Scale bar for the TEM images in (D), (E) and (F) is 50 nm. (G) Schematic
representation of the nanoflask. (H) AFM images of the nanoflask. Scale bar is 75 nm. (I) TEM
images of the nanoflask, randomly deposited on TEM grids. The cylindrical neck and rounded bottom
of the flask are clearly visible in the images. Scale bar is 50 nm.
•Han, D. et al. DNA Origami with Complex Curvatures in Three-Dimensional Space. Science 332,
342–346 (2011).
•

Carmel J Caruana, BioMedical Physics, Institute of Health Care, University of Malta
Vladan Bernard Deparment of Biophysics Lf MU
Dendrimers
•Dendrimers are globularly shaped polymers composed of branched repeating units leading off a
central core (like a tree, snowflake). •Biodendrimers are dendrimers made of repeating units known
to be biocompatible or biodegradable in vivo to natural metabolites. •The cavities present in
dendrimers can be used as binding sites for smaller molecules - effectively the dendrite becomes a
nanosized ‘container’ for various molecules.
•
pglsa-g4
polymer units
cavity
antigen
drug

Carmel J Caruana, BioMedical Physics, Institute of Health Care, University of Malta
Vladan Bernard Deparment of Biophysics Lf MU
Dendrimers: Medical Applications – Multifunctional nanosized containers (‘Platforms’)
/class=left width=

Carmel J Caruana, BioMedical Physics, Institute of Health Care, University of Malta
Vladan Bernard Deparment of Biophysics Lf MU
Fullerenes (and nanotubes)
•Carbon molecules in the shape of a hollow sphere, ellipsoid, tube or ring.
•Cylindrical fullerenes are often called nanotubes.
•The smallest fullerene is C60 (i.e., 60 C atoms)
•Other atoms can be trapped inside fullerenes e.g., La@C82  (lanthanum)
•SWNT - single walled nanotubes
•MWNT - multiwall carbon nanotube
•
fullerene

Carmel J Caruana, BioMedical Physics, Institute of Health Care, University of Malta
Vladan Bernard Deparment of Biophysics Lf MU
•The first fullerene molecule was discovered and prepared in 1985 by Richard Smalley et al.
•Nanotubes are cylindrical fullerenes. These tubes of carbon are usually only a few nanometres
wide, but they can range from less than a micrometer to several millimeters in length. They often
have closed ends, but can be open-ended as well. There are also cases in which the tube reduces in
diameter before closing off. Their unique molecular structure results in extraordinary properties,
including high tensile strength, high electrical conductivity, high ductility, high heat
conductivity, and relative chemical inactivity •Fullerenes can be made to be absorbed by HeLa
cells. The C60 derivatives can be delivered to the cells by using the functional groups
L-phenylalanine, folic acid, and L-arginine among others. The purpose for functionalizing the
fullerenes is to increase the solubility of the molecule by the cancer cells. Cancer cells take up
these molecules at an increased rate because of an upregulation of transporters in the cancer cell,
in this case amino acid transporters will bring in the L-arginine and L-phenylalanine functional
groups of the fullerenes. Once absorbed by the cells, the C60 derivatives would react to light
radiation by turning molecular oxygen into reactive oxygen which triggers apoptosis This research
shows that a reactive substance can target cancer cells and then be triggered by light radiation,
minimizing damage to surrounding tissues while undergoing treatment.
Fullerenes and nanotubes

Carmel J Caruana, BioMedical Physics, Institute of Health Care, University of Malta
Vladan Bernard Deparment of Biophysics Lf MU
Fullerenes (and nanotubes)
•
•Creating three-dimensional nanounits is not just the property of carbon, this ability have other
atoms too, e.g. molecules such as boron nitride (BN). This material also produces similar
formations such as carbon tubes, rings or fullerenes, including the possible closure of an atom of
another element into the created „cage“ (in this case the atom of Fe).
T. Oku et al. / International Journal of Inorganic Materials 3 (2001) 597 –612

Carmel J Caruana, BioMedical Physics, Institute of Health Care, University of Malta
Vladan Bernard Deparment of Biophysics Lf MU
Nanotubes – aplication (future???)
•Crystallized hydroxyapatite on the surface of modified nanotubes (University of California,
osel.cz)
1126904837
Utilization of nanotubes in medicine is experimentally demonstrated in experiments with bone tissue
substitutes. In this case the nanotubes (with modified surface compounds of phosphorus and sulfur)
are a substitute of collagen, which binds to crystalline hydroxyapatite and so creates a very
strong and compact bone tissue.
The benefit of this technology is far greater strength of the structures.
A possible disadvantage is the potential toxicity of fullerens and derived compounds (R E.
Oberdörster, Southern Methodist University, Dallas, New Scientist, March 2004), but it can be
avoided by the re-modification of surfaces (eg, by atoms of  Fe).
Bone tissue

Carmel J Caruana, BioMedical Physics, Institute of Health Care, University of Malta
Vladan Bernard Deparment of Biophysics Lf MU
Nanotubes – aplication (future???)
•Antibacterial effects
Results of studies show that surfaces treated with carbon nanostructures (fullerens, graphens)
themselves exhibit antibacterial properties.
Another use of carbon nanostructures is reatment of surfaces (eg, surgical instruments, equipment
of hospital rooms, ...) in conjunction with enzymes. By attaching nanotubes enriched with enzymes
on surfaces various medical instruments its own surface will increase, which corresponds to the
increasing interaction of the enzyme and subsequent enzymatic degradation of bacteria.
•Cytostatic therapy
Bhirde et al., In Targeted killing of cancer cells in vivo and in vitro with EGF-directed carbon
nanotube-based drug delivery, ACS Nano 3 (2009) describes the use of multiple wall nanotubes for
targeted cytostatic treatment. The principle is the linking of cisplatin with epidermal growth
factor by using nanotubes and subsequent binding of this complex to the receptors of growth factor
on tumor cells.
•
cell
cisplatin
Binding molecules
nanotube

Carmel J Caruana, BioMedical Physics, Institute of Health Care, University of Malta
Vladan Bernard Deparment of Biophysics Lf MU
Fullerenes: Medical Uses
•Carbon nanotube involving catheters (nanotubes have Young’s modulus 5 times greater that of
steel!)
•Nanotube-based “cold” cathodes (emit electrons freely without need of thermionic emission). It
will change conventional x-ray tube technology because of no need of a high power source and are
exceptionally durable. Nanotube based small X-ray tubes for radiation therapy inside the body
(brachytherapy) can be expected.
•Fullerenes with gadolinium are 5 times better MRI contrast agents than those used presently.
•Multifunctional platforms: binding specific antibiotics to the fullerene to target resistant
bacteria and cancer cells. Fullerenes are not very reactive and are insoluble in many solvents.

Carmel J Caruana, BioMedical Physics, Institute of Health Care, University of Malta
Vladan Bernard Deparment of Biophysics Lf MU
Nanotubes as wires
Nanotubes are currently the strongest material. The diameter of Single Wall Carbon Nanotubes
(SWCNT) is from 1 nm to 50 nm. Electrical properties are different according to the arrangement of
atoms C in the tube (the molecular structure influences the orientation of bonds). Depending on the
structure of bonds between carbons we can have Z (zigzag) or a A (armchair) configuration. "Z" acts
as a metal, "Armchair" as a semiconductor.
Depending on the structure of carbon nanotubes, the nanotube behaves as a metal or as a
semiconductor (or even a superconductor!). See so called "Armchair Quantum Wire„ elsewhere.
They can be also used (as superconductors) for generation of strong magnetic field, i.e. for MRI
Rice University - http://www.ece.rice.edu/~irlabs/aqw.htm

Carmel J Caruana, BioMedical Physics, Institute of Health Care, University of Malta
Vladan Bernard Deparment of Biophysics Lf MU
Carbon nanowires
•carbon nanowires, conductive, entangled nanofibers for "bridging" scarred heart tissue after a
heart attack and acting as an electrical signal transfer
Schema „První in vivo rekonstrukce přirozeného elektrického signálu pomocí syntetického materiálu“.
Kredit: Texas Heart Institute.
McCauley et al.,Circulation: Arrhythmia and Electrophysiology (2019).

Carmel J Caruana, BioMedical Physics, Institute of Health Care, University of Malta
Vladan Bernard Deparment of Biophysics Lf MU
Nanopores
•The pores of nanometer diameter become exploited in biology. •They are used to regulate the flow
of ions or molecules through the otherwise impermeable membranes.
Ultra-Thin%20Silicon%20Nitride%20Membranes%20as%20Nanosieves-1
Nanopores drilled by a focused-ion-beam in a 10 nm thick silicon nitride membrane. The scale bar is
60 nm.
Ref: H.D. Tong, H.V. Jansen, V.J. Gadgil, C.G. Bostan, J.W. Berenschot, C.J.M. van Rijn, and M.
Elwenspoek, Nano Lett. 4, 283, (2004).

Carmel J Caruana, BioMedical Physics, Institute of Health Care, University of Malta
Vladan Bernard Deparment of Biophysics Lf MU
Nanopores: Medical Applications: DNA sequencing
•As the DNA molecule passes through the nanopore, different bases lead to different drops in the
current and hence can be identified.
•Such sequencing, could revolutionize the field of genomics, as sequencing could be carried out in
a matter of seconds – very fast
•Other applications of this technique include separation of single stranded and double stranded DNA
in solution, and the determination of length of biopolymers.
system for detection DNA with a nanopore
http://www.ks.uiuc.edu/Research/nanopore/

Carmel J Caruana, BioMedical Physics, Institute of Health Care, University of Malta
Vladan Bernard Deparment of Biophysics Lf MU
Nanocrystal
•A nanocrystal is a crystalline particle with at least one dimension less than 100 nm.
•Semiconductor nanocrystals in the sub-10nm size range are often referred to as ‘quantum dots’. A
quantum dot has a discrete quantized energy spectrum.
http://www.elec-intro.com

Carmel J Caruana, BioMedical Physics, Institute of Health Care, University of Malta
Vladan Bernard Deparment of Biophysics Lf MU
Nanocrystal
– Quantum dots
•Clusters of atoms forming the regular monocrystalline structures
•As quantum dots can be also called clusters of atoms created on suitable ground (use in
electronics, communication technologies, ...)
•They have discrete energy levels
•Fluorescence properties – wavelength of the excitation radiation is chosen according to the size
of core of quantum dots.
•Use – cell mapping, immunomapping, MRI contrast
Triple immunofluorescence using the quantum dots, Fountaine et al, Mod Pathol 2006, 19, 1181-1191

Carmel J Caruana, BioMedical Physics, Institute of Health Care, University of Malta
Vladan Bernard Deparment of Biophysics Lf MU
Nanocrystals : antibacterial effects
•implants effected by nanomaterials
•
• and
•
• nature implants without nanomaterials
1152482751
According to Thomas J. Webster from Brown University, USA, it is possible to use nanocrystals of
titanium and zinc oxides to modify the surface of implants - nanostructuring method. Its nature
lies in multiple magnification of the surface of material by applying layers of nanocrystals
(proces of roughening), such as in the case orthopaedic implants. It helps to increase adhesion of
the tissue cells and accelerate the "healing". Another important function of such a modified
surface is the antimicrobial function, where the presence of zinc oxide nanocrystals suppresses the
formation of microbial films.

Carmel J Caruana, BioMedical Physics, Institute of Health Care, University of Malta
Vladan Bernard Deparment of Biophysics Lf MU
•Liquid glass - the source material in this case is ordinary silica sand (silicon oxide)
nanoparticles, which are added to the mixture with water or ethanol - according to the surface on
which liquid glass is applied (using spray). Nothing other is needed, the liquid glass at the site
sticks by physical forces (which are ubiquitous in nanoworlds).
•Sprayed liquid glass creates a waterproof layer with thickness of about 100 nanometers, which
represents only 15-30 molecules.
Liquid glass has a very durable antibacterial effects. It is antimicrobial, because liquid glass
reduced adhesion of microbes on the treated surface.
•Liquid glass was been tested  in a hospital in Lancashire, where the staff used surgical
equipment, implants, catheters, … all threated by this interesting nanomaterial. The result of the
tests was an increase in antibacterial protection
Nanocrystals: liquid glass

Carmel J Caruana, BioMedical Physics, Institute of Health Care, University of Malta
Vladan Bernard Deparment of Biophysics Lf MU
Nanofibers – recently existing and often used
•Nanofibers are fibers with diameters in the nanometer range. •Nanofibers can be generated from
different polymers and hence have different physical properties and application potentials.
•Biodegradability, biocompatibility
• Examples of natural polymers include collagen, cellulose, silk fibroin, keratin, gelatin and
polysaccharides •Examples of synthetic polymers include poly(lactic acid) (PLA), polycaprolactone
(PCL), polyurethane (PU) …

Carmel J Caruana, BioMedical Physics, Institute of Health Care, University of Malta
Vladan Bernard Deparment of Biophysics Lf MU
Nanofibers
•There exist many different methods to make nanofibers, including drawing, electrospinning,
self-assembly, template synthesis, and thermal-induced phase separation.
C:\Users\Bernard\Desktop\nanospider.jpg

Carmel J Caruana, BioMedical Physics, Institute of Health Care, University of Malta
Vladan Bernard Deparment of Biophysics Lf MU
Nanofibers
•Applications :
•Tissue engineering (extracellular matrix)
•Drug delivery (antibiotics and anticancer drugs have been successfully encapsulated)
•Cancer diagnosis (chips)
•Optical sensors
•
•
•
•

Carmel J Caruana, BioMedical Physics, Institute of Health Care, University of Malta
Vladan Bernard Deparment of Biophysics Lf MU
Nanofibers
skeleton of trachea
surface protection „new skin“

Carmel J Caruana, BioMedical Physics, Institute of Health Care, University of Malta
Vladan Bernard Deparment of Biophysics Lf MU
magnetotactic
Magnetic nanoparticles
•Magnetic nanoparticles - characterized by magnetic
moment μ and by interaction with the external
• magnetic field H
•
•The natural incidence of magnetic nanoparticles in nature
- Magnetospirillum magnetotacticum - magnetite (organelle magnetosom)
bee, termite, pigeon, dolphin
•
•The use in medicine, biomedicine:
•transport / separation / immobilisation of magnetic nanoparticles or molecules conjugated with the
nanoparticles by an external magnetic field - the separation of DNA / RNA, targeted drug delivery
•heating (energy transfer from the external magnetic field on magnetic nanoparticles) - eg magnetic
intercellular hyperthermia for cancer treatment
•increasing MRI contrast signal - as a contrast agent Resovist ® (iron oxide coated
karboxydextranem) for examination of the liver
500 nm

Carmel J Caruana, BioMedical Physics, Institute of Health Care, University of Malta
Vladan Bernard Deparment of Biophysics Lf MU
500 nm
MRI contrast agents
Schematic representation of the use of magnetic nanoparticles in medicine (Kumar and Mohammad,
2011)
Magnetic nanoparticles

Carmel J Caruana, BioMedical Physics, Institute of Health Care, University of Malta
Vladan Bernard Deparment of Biophysics Lf MU
Magnetic nanoparticles :
 Temperature-controlled transport of drugs
Temperature-controlled transport of drugs by using heating of magnetic nanoparticles by action of
external magnetic field (hysteresis during heating).
a)mobilization of substances (drugs) bound to the nanoparticle through thermolabile bond (by
changing the temperature of nanoparticles due to applications of magnetic field
b)
 b) mobilisation of substances (drugs) from the polymer envelope which also contains magnetic
nanoparticles. The release of substances is enabled by the presence of micro-cracks that occur
during heating of the nanoparticles present in the polymer by exposure to changing magnetic field
Kumar, Mohammad, Magnetic nanomaterials for hyperthermia-based therapy and controlled drug
delivery, Adv. Drug Deliv. Rev. (2011)

Carmel J Caruana, BioMedical Physics, Institute of Health Care, University of Malta
Vladan Bernard Deparment of Biophysics Lf MU
Magnetic nanoparticles
Kumar, Mohammad, Magnetic nanomaterials for hyperthermia-based therapy and controlled drug
delivery, Adv. Drug Deliv. Rev. (2011)
Overview of magnetic nanoparticles and their possible use

Carmel J Caruana, BioMedical Physics, Institute of Health Care, University of Malta
Vladan Bernard Deparment of Biophysics Lf MU
Nanocrystal: Medical applications: Contrast Media for MRI Imaging

Carmel J Caruana, BioMedical Physics, Institute of Health Care, University of Malta
Vladan Bernard Deparment of Biophysics Lf MU
Magnetic nanoparticle: Contrast Media for MRI Imaging
TEM microscopy - magnetite nanoclusters consisting of magnetite nanoparticles
The use of magnetic nanoparticles as contrast agents for MRI views, in this case, monitoring the
distribution of stem cells (containing these nanoclusters) in mouse brain.
MRI signal of magnetic nanoparticle
Chunfu Zhang et al., High MR sensitive fluorescent magnetite nanocluster for stem cell tracking in
ischemic mouse brain, Nanomedicine: Nanotechnology, Biology and Medicine, Available online 8 April
2011

Carmel J Caruana, BioMedical Physics, Institute of Health Care, University of Malta
Vladan Bernard Deparment of Biophysics Lf MU
Nanowires
•A nanowire is a wire of diameter of the order of nm.
•Photo: A light-conducting silica nanowire wraps a beam of light around a strand of human hair. The
nanowires are flexible and can be as slender as 50 nanometers in width, about one-thousandth the
width of a hair.
•This is far smaller than the smallest capillary in the body! That means nanowires could, in
principle, be threaded through the circulatory system to any point in the body without blocking the
normal flow of blood or interfering with the exchange of gases and nutrients through the
blood-vessel walls
nanowire_light

Carmel J Caruana, BioMedical Physics, Institute of Health Care, University of Malta
Vladan Bernard Deparment of Biophysics Lf MU
Nanowires: Medical Applications – Brain studies and therapy - fantasy
•Bunch of nanowires being guided through the circulatory system to the brain. Once there, the
nanowires would spread out branching into tinier and tinier blood vessels. Each nanowire would then
be used to record the electrical activity of a single nerve cell, or small groups of nerve cells
(better than PET or fMRI!) giving the ability to pinpoint damage from injury and stroke, localize
the cause of seizures, and other brain abnormalities. It's long been known that people with
Parkinson's disease can experience significant improvement from direct stimulation of the affected
area of the brain with electrical pulses. Indeed, that is now a common treatment for patients who
do not respond to medication. But the stimulation is currently carried out by inserting wires
through the skull and into the brain, a process that causes scarring of brain tissue. The hope is,
by stimulating the brain with nanowires threaded through pre-existing blood vessels, doctors could
give patients the benefits of the treatment without the damaging side effects.
•
09-07-2005-1
Prof. Bernard NYSTEN , Université catholique de Louvain

Carmel J Caruana, BioMedical Physics, Institute of Health Care, University of Malta
Vladan Bernard Deparment of Biophysics Lf MU
Nanowires: Medical Applications – Environmental Molecular Sensors
•Compared to ordinary fiber optic cable, which appears to the naked eye as a uniform glowing line,
nanowires have a beaded appearance when viewed under magnification. That's because unlike a normal
fiber, which confines light within its walls, minuscule particles of dust along the nanowires'
surface can scatter the light beam. This sensitivity to surface contaminants could lead to use of
the nanowires as molecular sensors. •One could fit the surface of the wire with receptors for
environmental molecules. If those target molecules are present, they'll attach to the receptors and
blobs of tiny lights will be seen when the wires are illuminated.
•
light
nanowire
Blobs of lights signalised attached molecul

Carmel J Caruana, BioMedical Physics, Institute of Health Care, University of Malta
Vladan Bernard Deparment of Biophysics Lf MU
Nanowires: Medical Applications: Biomolecular Sensors
Roszek  et al.
Medical Nanotechnology

Carmel J Caruana, BioMedical Physics, Institute of Health Care, University of Malta
Vladan Bernard Deparment of Biophysics Lf MU
Robotic nanoworld
•Nature 2010 - Molecular robots guided by prescriptive landscapes – Lund et al.
•Nature 2010 - Molecular robots guided by prescriptive landscapes - Lund et al.
The authors of this paper presented "nano-spider" which is consist of protein and DNA and  that can
move along the trajectory by using pre-programmed short ss DNA chains. Nano-spider has the body
formed by the protein streptavidin. Despite biotin (vitamin H) are linked to him four short
stretches of single-stranded DNA / enzyme. The total size of nano-spider is 4 nm. The trajectory is
given by compatibility ss DNA chains that are on pads and ss DNA chains forming the "legs". It is
controlled by the commands "start", "change the direction" and "stop„.
DNA-based nanorobotics
nature09012-f1

Carmel J Caruana, BioMedical Physics, Institute of Health Care, University of Malta
Vladan Bernard Deparment of Biophysics Lf MU
Robotic nanoworld
•Princip of moving of „nanocar“ (Rice University)
nano-robotics based on organic molecules
1145197120
The size of molecules of „nanocar" are less than 4 nm, "wheels" are formed by molecules of
p-carborane, "engine" of combination of aromatic rings. After iradiation by electromagnetic wave ,
it is absorbed by central molecule, and this begins to rotate on the gold surface and move the
whole "nanocar". The highest speed is 2 nm per minute.
www.newscientist.com
1145197068
http://www.youtube.com/watch?v=lASdcW-BtiU
http://www.youtube.com/watch?NR=1&v=57GYz69GFbI

Carmel J Caruana, BioMedical Physics, Institute of Health Care, University of Malta
Vladan Bernard Deparment of Biophysics Lf MU
Health Risks
•Nanoparticles are able to cross biological membranes and access cells, tissues and organs that
larger-sized particles normally cannot. They can gain access to the blood stream after inhalation
or ingestion. At least some can penetrate the skin. Once in the blood stream, they can be
transported around the body and are taken up by organs and tissues including the brain, heart,
liver, kidneys, spleen, bone marrow and nervous system. Unlike larger particles, they may be taken
up by cell mitochondria and the cell nucleus. Studies demonstrate the potential for DNA mutation
and induce major structural damage to mitochondria, even resulting in cell death.
•Hundreds of consumer products incorporating nanoparticles are now on the market, including
cosmetics, sunscreens, sporting goods, clothing, electronics, baby and infant products, and food
and food packaging.

Carmel J Caruana, BioMedical Physics, Institute of Health Care, University of Malta
Vladan Bernard Deparment of Biophysics Lf MU


Carmel J Caruana, BioMedical Physics, Institute of Health Care, University of Malta
Vladan Bernard Deparment of Biophysics Lf MU
Titanium dioxide nanoparticles in food and personal care products, Weir A et al, Environ Sci
Technol. 2012, 46
•Average day quantity per adult   (in USA) - 1 mg nano TiO2 per 1 Kg of human weight
•
•Approx  5000 tonne (5 000 000 kg) of nano TiO2 was used in products of daily care.
•
•
•
8_titan-beloba_0
titanium white or E 171, average man 80 kg * 365 day * 1 mg = 29 200 mg = 29,2 g TiO2   ( one sugar
cube cca 10 g, teaspoon of flour cca 7 g)
barva-olejova-beloba-titanova-40-ml-original

Carmel J Caruana, BioMedical Physics, Institute of Health Care, University of Malta
Vladan Bernard Deparment of Biophysics Lf MU
nanomaterials are everywhere around us

Carmel J Caruana, BioMedical Physics, Institute of Health Care, University of Malta
Vladan Bernard Deparment of Biophysics Lf MU
Author:
Vladan Bernard
Carmel J. Caruana
Content collaboration:
 Vojtěch Mornstein
Last revision: November 2021