Medical Design Briefs - May 2021 - 40

GlobAl

INNOVATIONS

Biodegradable Nanoprobe Illuminates Tumors Brightly and
Precisely
Imperial College London, London, UK

o highlight tumors in the body for
cancer diagnosis, doctors can use
tiny optical probes (nanoprobes)
that light up when they attach to tumors.
These nanoprobes allow doctors to
detect the location, shape, and size of
cancers in the body.
Most nanoprobes are fluorescent: they
absorb light of a specific color, like blue,
and then emit back light of a different
color, like green. However, as tissues of
the human body can emit light as well,
distinguishing the nanoprobe light from
the background light can be tough and
could lead to the wrong interpretation.
Now, researchers at Imperial College
London have developed new nanoprobes,
named bioharmonophores and patented at
Imperial, which emit light with a new type
of glowing technology known as second
harmonic generation (SHG).
After testing the nanoprobes in zebrafish embryos, the researchers found that
bioharmonophores that were modified
to target cancer cells highlighted tumors
more brightly and for longer periods
than fluorescent nanoprobes (see Figure
1). Their light can be easily spotted and
distinguished by the tissue generally
emitted light, and they also attach pre-

Artistic representation of the bioharmonophore
structure. (Credit: Konstantinos Kalyviotis)

Human Cancer Cells

p32-Targeted
Bioharmonophores

Bioharmonophore-Labeled Tumors

c1
2 dpf embryos
c1

3 dpf embryos

Synthesis of
Bioharmonophores

5 dpf embryos
c2

c1'

Triphenylalanine

Peptide
Self-Assembly

Encapsulated
Peptide Assemblies

c2'

Bioharmonophores

Single targeted cells

Imaging of
Single
Cancer Cells
Injection of Targeted
Bioharmonophores

c3'

Fig. 1 - Nanoprobes tested in zebrafish could
help detect cancer more accurately. Purple cancer cells are labeled using bioharmonophores
(white label). (Credit: Pantazis Lab, Imperial
College London)

cisely to tumor cells and no healthy cells,
making them more precise in detecting
tumor edges (see Figure 2). The findings
are published in ACS Nano.
" Bioharmonophores uniquely combine features that could be great for cancer diagnosis and therapy in clinical
practice and could eventually improve
patient outcomes following further
research, " says lead researcher Dr.
Periklis Pantazis of Imperial's department of bioengineering.
Bioharmonophores are both biocompatible and biodegradable because they
are made of peptides. To investigate precise tumor detection, the researchers first
injected zebrafish embryos with malignant cancer cells, which allowed tumor
cells to proliferate unchecked. Twentyfour hours later, they injected bioharmonophores, which were modified to target p32 peptide molecules that are specifically found in tumor cells. They then
used imaging techniques at Imperial's
Facility for Imaging by Light Microscopy
to study how well the modified bioharmonophores detected the tumors.
They found that bioharmonophores
had outstanding detection sensitivity,
meaning that they attached to specific
tumor cells but not to healthy ones.
Fluorescence-enabled nanoprobes tend
to attach less specifically, meaning they
can misrepresent healthy cells as tumor
cells, or vice versa.

www.medicaldesignbriefs.com

Cov

ToC

Targeted MDA-MB-435 DsRed
Melanoma Cancer Cells

c4'

Fig. 2 - Diagram showing assembly of bioharmonophores, alongside contrasting images of
highlighted tumors using bioharmonophores
and other techniques. (Credit: Pantazis Lab,
Imperial College London)

They also found that, unlike fluorescence, bioharmonophores did not
'bleach,' meaning they did not lose their
ability to emit light over time. In addition, the light emitted by bioharmonophores did not saturate as happens with fluorescent nanoprobes.
" It is very important that tumor
nanoprobes highlight cells specifically
and clearly for cancer diagnosis, " says
Pantazis. " Our proof-of-concept study
suggests that the very bright bioharmonophores could be powerful tools in
diagnosing cancer and targeting treatments in the coming years. "
The manufacture of bioharmonophores is cheap, reproducible, and
scalable and takes around two days at
room temperature. They now need to
be tested in mammals to identify how
well the findings translate beyond
zebrafish.
The researchers are also looking into
how bioharmonophores could be used
to guide surgical interventions during
cancer surgery, as well as how they could
generate light at different frequencies to
potentially help kill tumor cells with
high precision.
This work was funded by the Royal
Society, Wellcome Trust, the Swiss
National Science Foundation, the European Union, and the Swiss National
Centre of Competence in Research.
This article was written by Caroline Broga,
Communications and Public Affairs, Imperial College London. For more information,
visit www.imperial.ac.uk.

Medical Design Briefs, May 2021

http://www.imperial.ac.uk http://www.medicaldesignbriefs.com

Medical Design Briefs - May 2021

Table of Contents for the Digital Edition of Medical Design Briefs - May 2021