BIONANOTECHNNOLOGY:
NANOMEDICINE –
BNT30306_2023
+ What is nanotechnology?
It is an interdisciplinary field of research at the crossing of biotechnology and nanotechnology with
application areas ranging from material science to medicine.
All chemistry pillars come together in one: it includes natural/non-natural materials, solid7soft
nanoparticles (NPs), covalent/non-covalent interactions, relevant spectroscopic techniques and many
others.
We will talk about many different materials like bulky balls, quantum dots and carbon nanotubes.
In nano biotech the approached can be a top down, where from a big molecule (piece), it is shaped
something much smaller and specific, or a bottom-up approach, which from the simplest molecule it
is built a specific nanoparticle much larger by depositing atoms on a substrate.
Nanomedicine however it is about the application of nanomaterials in medicinal applications that
covers a size range between 1-100nm.
Note: that nanoparticles are much bigger than one as a chemist might think by the name. They are
huge particles usually.
Microtechnology vs nanotechnology:
There are several reasons why smaller sizes are better. If we want to mimic nature´s creations, we
must follow nature´s format at the molecular level. Usually, smaller sizes are less invasive to the body
and less likely to be rejected by the immune system if they are implanted in vivo. Nanostructures,
due to their small size they experience novel physical, chemical and biological properties. (small size
with more functionality per unit area).
“Small” technology has been divided into microtechnology and nanotechnology.
Microtechnology relates to microelectromechanical systems, for example, microfluidics and
microarrays. Nanotechnology relates to molecules, nano-size devices, and nanoparticles. The
difference between microtechnology and nanotechnology lies in (a) their size range, (b) type of
synthetic materials, and (c) their method of manufacturing (topdown vs. bottom-up).
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, 1. BIONANOTECH: TOWARDS NANOMEDICINE
Upon radiation of molecules there are 4 different
outcomes:
a) Transmission no interference just
transmission.
b) Absorption
c) Absorption that leads to fluorescence or
molecular vibration.
d) Scattering in which the energy bounces
away.
The difference between situation b and c is
that the absorption that transforms into
fluorescence or molecular vibration can be
monitored and measured.
Nanomaterial can be used to improve the biological sensing in the biomolecular realms,
since they exhibit unique and useful optical behaviours.
1.1. HARD NANOPARTICLES IN NANOMEDICINE:
Golden particles and quantum dots will be the main ones discussed, which can have applications in
the diagnostics and/or therapeutics.
Golden particles:
The golden particles have different sizes, and depending on them they radiate a different colour.
They are very stable particles and very easy to synthesise. They have a pronounce excitation peak in
the visible spectrum and intense surface fields polarize the local volume around the nanoparticles.
Small golden particles are red, whereas big ones are blue/purple.
During centuries there has been an ongoing drugs and dyes relationship and actually it has been
used since decades to make the glass beads of the cathedrals, as the advantage over any other
colourant (if organic) used. When the glass is being made it requires to be burned at very high
temperatures that will decompose the colorant. With NP that will not happen.
NP have many medical applications, for example with
a corona test.
It consists of an optical probe in antibody-linked
immunoassays.
Moreover, metals like gold have been introduced in
society even in food and drinks.
Gold is a novel metal and therefore is barely never
oxidizes, which then cannot be absorbed by the body
when ingested.
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,Silver on the other hand is also a novel metal nevertheless, it is not as good as gold, and it can oxidize
into silver ions. It has been debated whether silver could fight an infection by releasing silver ions
that will disturb bacteria metabolism.
Quantum dots (QDs):
They are fluorescence inorganic semiconductor nanoparticles typically ranging from 2-10nm in size.
They possess a really high fluorescence and photostability.
They have a very broad absorption and a sharp emission spectrum that are tuneable by particle size,
allowing multiplexing in a mixed population of QDs that can be excited by a single excitation source.
Advantages of using hard nanomaterials in biological sensing is that they are robust and highly
sensitive, whereas the current technique use passive labelling, are labour intensive, require washing,
heating, incubation and in the case of organic dyes they have a very poor solubility.
However, the main challenges of these NPs is the possibility of reproducible of high-quality NPs and
maximizing performance in physiological conditions.
1.2. THREE KEY COMPONENTS TO UNDERSTAND BETTER
NANOPARTICLES FOR BIOSENSORS:
The presence of high-quality nanoparticles with precisely engineered surface and biosensing
mechanism is needed for high sensitivity and specific biosensors as nanoparticles.
However, the presence of high-quality nanoparticles is non-existent as the replication of identical
nanoparticles is truly hard to obtain. Normally there is a size distribution evenly over the number of
nanoparticles you produce where none of them are identical but highly similar. Therefore, protocols
to produce identical NP (specially for drugs) in large quantity is yet needed.
To understand better how this can be slightly achieved you need to understand the chemistry behind
the nanoparticle core, the surface and the biosensing mechanism.
Nanoparticles core:
To understand the core formation of a NP you can use different
methods like:
In in situ radiation, it can be used while making the
compounds without disturbing them. In computer
simulation it is important to understand the position of the
molecules in the surface of the core and in between the
different atoms.
NPs for biosensing need to be chemically robust to
withstand complex conditions and show minimal
perturbation to the probed system (low or no toxicity). They
should also produce intense but switchable responses to
incident light yielding in a strong signal change upon analyte interaction.
In the case od QDs excellent optical properties, but heavy metal particles that can lead to
toxicity and might prohibit the wide-scale use.
There are now free heavy metal alternatives, yet they have not surpassed the excellent
properties of QDS.
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, Fluorescent NPs absorb high-energy light and emit at a lower energy. New generations is
reversed, where they absorb at low-energy light and emit at higher energy. Very convenient
since you can radiate at near infrared, which penetrates more in the tissue and avoid natural
fluorescent of the tissue.
Nanoparticles surface:
Usually, surface control is much easier in vitro settings. However, in real cell conditions there can be
many unspecific interactions, changes in the Ph (by formation of aggregates for example) and salt ion
charge screening.
Therefore, it is not trivial what can be added in the surface of the molecule (later there will be a
section specific on it).
Surface covering of the NP offers a barrier between the core and its environment.
It is usually formed by a layer of capping molecules that bind directly to the surface and ideally stops
particle aggregations. Disperses them in water, resist non-specific absorption etc.
The interface between NP core and biological environment is a key area that needs to be engineered
carefully for an optimized NP functionalization.
Because of the hostile environment that NP face the capping agents serve a protection layer too.
They should be compact and highly protectiveThicker more protection.
The biosensing mechanism that modulate NP signals in response to analyte interaction are usually
governed by distance-dependent interactions across the capping layer.
Thinner capping layer has a stronger signal modulation.
Polymeric capping is one of the options with many surface binding groups and increased control but
hard to obtain a compact layer, due to their bulkiness.
Biosensing mechanisms:
How do the nanoparticle behave before detection of the target and after the detection of the target,
and how as scientists can we monitor this.
Usually there is a fluorophore or a florescent molecule that upon target interaction there is a change
between luminescence to dark or dark to luminescent. But note that many other possibilities are
made.
The modulation of NP signals by interaction with target analytes is governed by the architecture of
surface-bound biosensing mechanisms:
The way constituent biomolecules are conjugated to the NP.
The signalling modes employed.
The analyte-receptor mechanism.
Ideal bioconjugation should be simple, high yield and nondamaging the nanoparticles and preferably
should require no intermediate reagents binding of biotinylated biomolecules to streptavidin
coated NPs achieves all of this characteristics.
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