YSM Issue 93.2

FOCUS
Nanoscience
at once,” Piotrowski-Daspit explained.
This method could provide researchers
opportunities to better understand combination
therapies in humans as well.
Overcoming Obstacles
The researchers faced a few challenges
on their path to developing this improved
microscopy method. First, a major
concern with nanoparticle research
is the possibility that the fluorescent dye
(which is visualized) and the nanoparticle
itself have unexpectedly separated, so
the dye is no longer indicating where the
nanoparticle is. To address this, the team
ordered a commercially available polymer
that is chemically linked to a fluorescent
dye, and then imaged both the
polymer and a separate encapsulated dye.
“The observation that they colocalized
served as evidence that going forward, if
we look only for the encapsulated dye, we
can be confident that it is also with the
nanoparticle of interest,” Bracaglia said.
Another concern was that measuring fluorescent
agents might not be as accurate
as measuring radiolabeled agents, so the
team carefully compared their experimental
half-lives with examples from literature.
Not only did they confirm similar
half-life values, but their method was
also less complicated and more accessible
for the average lab, which may not have
equipment for measuring radioactivity.
Future Projects
Armed with a more effective method to
measure circulation half-lives of drugs,
the Saltzman research group plans to
ABOUT THE AUTHOR
rapidly screen through their nanoparticle
libraries. “We are excited to see where
these new nanoparticles go and how long
they stay in the blood, and to learn more
about how changes to physical and chemical
properties can affect drug delivery
success,” Bracaglia said.
An upcoming challenge for these researchers
involves what happens after
nanoparticles are delivered into circulation.
Because the liver functions to detoxify
drugs from the blood, nanoparticles
often accumulate in the liver instead
of the desired target organ. The researchers
hope to discover ways to bypass
the liver, using “decoy” nanoparticles.
“These molecules potentially may be
used to pre-treat and take up residence in
the liver, such that anything that comes
afterwards can remain in circulation longer
and reach other organs,” Piotrowski-Daspit
explained.
The main advantage of this novel protocol
is that the improved quantitative
fluorescent microscopy has drastically
reduced sample blood volume. Previous
limitations from sample blood volume
often prevented experiments involving
essential animals with rare tumors or diseases.
“You normally don’t want to waste
these animals doing a half-life experiment.
If you’re treating the tumor, you
want to save these animals to see if the
treatment worked,” Bracaglia said. Drug
circulation, however, might significantly
differ between non-experimental and
diseased animals. With this new timeand-cost
effective, accessible microscopy
method, scientists may soon be able to
screen a wide range of therapeutic agents
and provide more accurate measurements
for preclinical studies, enabling researchers
everywhere to answer the growing
need for innovative drugs. ■
ANNA SUN
ANNA SUN is a senior in Jonathan Edwards College majoring in Molecular, Cellular and Developmental
Biology. She currently serves as Managing Editor for the . Outside of , she
studies riboswitches, volunteers in the hospital, and reads with New Haven youth. She also enjoys
dancing and exploring the food scene in New Haven with her friends.
THE AUTHOR WOULD LIKE TO THANK Laura Bracaglia, Alexandra Piotrowski-Daspit, and Mark
Saltzman for their time and thoughtful discussions about their research.
FURTHER READING
Bracaglia, L. G., Piotrowski-Daspit, A. S., Lin, C., Moscato, Z. M., Wang, W., Tietjen, G. T., & Saltzman, W.
M. (2020). High-throughput quantitative microscopy-based half-life measurements of intravenously
injected agents. PNAS, 117(7), 3502-3508.
Bracaglia, L. G., Piotrowski-Daspit, A. S., & Saltzman, W. M. (Personal interview, March 4, 2020).
FDA. (2018, January 4). Step 3: Clinical research. The Drug Development Process. https://www.fda.gov/
patients/drug-development-process/step-3-clinical-research
Smith, Yolanda. (2018, August 23). News Medical Life Sciences. https://
www.news-medical.net/health/What-is-the-Half-Life-of-a-Drug.aspx
Fluorescence fundamentals.
biological and biomedical research. , 14067-14090.
Saltzman Research Group. (n.d.). Our research. https://saltzmanlab.yale.edu/gallery/our-research
Le, J. (2019, June). Merck Manual Consumer Version. https://www.merckmanuals.
com/home/drugs/administration-and-kinetics-of-drugs/drug-administration
12 Yale Scientific Magazine September 2020 www.yalescientific.org