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Short chain PEGylation of Organic Small Molecule Dyes Can Regulate Their Clearance in The Kidney .pdf


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Short-chain PEGylation of Organic Small
Molecule Dyes Can Regulate Their Clearance in
The Kidney
Studying the body's different responses to small changes in ultra-small
nanomaterials is a very important and fundamental issue. These basic
research can not only help us understand our organism at the nano level more
clearly, but also have important guiding significance for regulating the
functionality and toxicity of nanomaterials. In the past few decades,
researchers have worked hard to study the relationship between small
changes in hard engineered nanomaterials and biological response and
discovered a series of size dependencies in both clearance and disease
targeting.
The biocompatibility, amphiphilicity, size controllability, and ability to modify the
biological characteristics of modified molecules make PEGylation the most
widely used bioconjugation chemistry in medicine. The removal of PEG
molecules by the glomeruli also has a size effect, that is, PEG molecules with
a molecular weight between 1500-4000 Da can quickly pass through the
glomerular filtration membrane, larger PEG molecules with MW in the range of
6000–40 000 Da have a stronger interaction with the glomerular filtration
membrane, resulting in their slower renal clearance efficiency. Because of this,
PEGylation has become a simple and commonly used chemical method for
regulating the blood residence time and clearance kinetics of small molecules.
However, because PEG molecules with a molecular weight of less than 10
kDa are rapidly filtered by the glomeruli, it cannot significantly and effectively
extend the residence time of small organic molecules in the blood. Based on
the current research, it is generally believed that PEGylation with a molecular
weight greater than 10,000 Da can effectively regulate (decrease) the kidney

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clearance rate of small molecules, but low molecular weight (<10000 Da)
PEGylation can only makes trivial contributions in tailoring the renal clearance
of small molecules. However, there is currently no systematic study on how
PEGylation of different sizes and less than 10 kDa affects the renal clearance
of small molecules.
In response to the above problems, Professor Zheng Jie of the University of
Texas at Dallas and the first author of this review, Dr. Du Bujie, chose a
representative near-infrared (NIR) -emitting organic dye (IRDye800CW) for a
series of PEGylation of different molecular weights (both less than 10 kDa,
PEG22, PEG45, PEG77, PEG110, PEG220) and study their biological
response. Traditionally, PEGylation with a larger molecular weight can more
effectively regulate kidney clearance of small molecules. However, the team of
Zheng Jie discovered a unique molecular weight size effect, namely PEG45
(molecular weight 2100 Da) can maximize kidney clearance of IRDye800CW
(figure 1). Further research found that PEG45 is unique because PEG45 not
only accelerates the glomerular filtration of IRDye800CW but also reduces its
role with basic biological tissues.
It is traditionally believed that PEGylation with a larger molecular weight can
more effectively regulate kidney clearance of small molecules. However, the
team of Zheng Jie discovered a unique molecular weight size effect, namely
PEG45 (molecular weight 2100 Da) can maximize renal clearance of
IRDye800CW (figure 1). Further research found that PEG45 is unique
because PEG45 not only accelerates the glomerular filtration of IRDye800CW
but also reduces its role with basic biological tissues. And the fast kidney
transport and reduced nonspecific interactions enable 800CW-PEG45 to
noninvasively light up the kidneys with high contrast index. (figure 2)。

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Figure 1, Source: American Chemical Society

Figure 2, Source: American Chemical Society

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The findings of this work highlight the importance of low molecular weight
PEGylation in regulating the flow rate of small organic dyes in organisms,
which will expand the application of small molecules in biomedicine. The
relevant results of this study were published in Bioconjugate Chemistry and
selected as ACS Editors' Choice. This project has received financial support
from NIH, Welch Research Foundation.
Biochempeg, a professional PEG derivatives supplier, is dedicated to
providing worldwide customers with PEGylation services and PEG dye
labeling for your research requirements.
Reference:
Tailoring Kidney Transport of Organic Dyes with Low-Molecular-Weight
PEGylation, Bioconjugate
Chem, https://doi.org/10.1021/acs.bioconjchem.9b00707


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