OPTIMAL PARTICLE SIZE FOR ANTICANCER NANOMEDICINES DISCOVERED
Nanomedicines
consisting of nanoparticles for targeted drug delivery to specific tissues and
cells offer new solutions for cancer diagnosis and therapy. Understanding the
interdependency of physiochemical properties of nanomedicines, in correlation
to their biological responses and functions, is crucial for their further
development of as cancer-fighters.
"To develop
next generation nanomedicines with superior anti-cancer attributes, we must
understand the correlation between their physicochemical properties --
specifically, particle size -- and their interactions with biological
systems," explains Jianjun Cheng, an associate professor of materials
science and engineering at the University of Illinois at Urbana-Champaign. In a
recent study, published in theProceedings
of the National Academy of Sciences, Cheng and his collaborators
systematically evaluated the size-dependent biological profiles of three
monodisperse drug-silica nanoconjugates at 20, 50 and 200 nm.
"There has been
a major push recently in the field to miniaturize nanoparticle size using novel
chemistry and engineering design," Cheng added. "While most current
approved anti-cancer nanomedicines' sizes range from 100-200 nm, recent studies
showed that anti-cancer nanomedicines with smaller sizes -- specifically of 50
nm or smaller -- exhibited enhanced performance in
vivo, such as greater tissue penetration and enhanced tumor
inhibition."
"Over the last
2-3 decades, consensus has been reached that particle size plays a pivotal role
in determining their biodistribution, tumor penetration, cellular
internalization, clearance from blood plasma and tissues, as well as excretion
from the body -- all of which impact the overall therapeutic efficacy against
cancers," stated Li Tang, first author of this PNAS article. "Our
studies show clear evidence that there is an optimal particle size for
anti-cancer nanomedicines, resulting in the highest tumor retention.
Among the three
nanoconjugates investigated, the 50 nm particle size provided the optimal
combination of deep tumor tissue penetration, efficient cancer cell
internalization, as well as slow tumor clearance, exhibits the highest efficacy
against both primary and metastatic tumors in vivo.
To further develop
insight into the size dependency of nanomedicines in tumor accumulation and
retention, the researchers developed a mathematical model of the
spatio-temporal distribution of nanoparticles within a spherically symmetric
tumor. The results are extremely important to guide the future research in
designing new nanomedicines for cancer treatment, Cheng noted. In addition, a
new nanomedicine developed by the Illinois researchers -- with precisely engineered
size at the optimal size range -- effectively inhibited a human breast cancer
and prevented metastasis in animals, showing promise for the treatment of a
variety of cancers in humans.
Cheng, a Willett
Faculty Scholar at Illinois, is affiliated with the departments of
Bioengineering and of Chemistry, the Beckman Institute for Advanced Science and
Technology, the Micro and Nanotechnology Laboratory, the Institute of Genomic
Biology, the Frederick Seitz Materials Research Laboratory, and University of Illinois
Cancer Center.
Tang, who obtained
his PhD degree from the University of Illinois with Jianjun Cheng, is currently
a CRI Irvington postdoctoral fellow at the Massachusetts Institute of
Technology. Collaborators and co-corresponding authors of the paper at Illinois
include Timothy Fan, associate professor, veterinary clinical medicine; Andrew
Ferguson, assistant professor, materials science and engineering; and William
Helferich, professor, food science and human nutrition.
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