Self-Quenched
Polysaccharide Nanoparticles with a
Reactive Oxygen Species-Sensitive Cascade for Enhanced Photodynamic
Therapy
Posted on 2020-06-16 - 11:34
Tumor
microenvironment (TME)-responsive nanocarrier systems that
keep the photosensitizer (PS) inactive during systemic circulation
and then efficiently release or activate the PS in response to unique
TME conditions have attracted much attention. Herein, we report novel
TME-responsive, self-quenched polysaccharide nanoparticles (NPs) with
a reactive oxygen species (ROS)-sensitive cascade. The PS, pheophorbide
A (PhA), was conjugated to a water-soluble glycol chitosan (GC) through
an ROS-sensitive thioketal (TK) linker. The amphiphilic GC–TK–PhA
conjugates could arrange themselves into NPs and remain photoinactive
due to their self-quenching effects. Upon reaching the ROS-rich hypoxic
core of the tumor tissue, the NPs release the PS in a photoactive
form by efficient, ROS-sensitive TK bond cleavage, thus generating
potent phototoxic effects. Following near-infrared irradiation, the
increase in locoregional ROS levels further accelerates the release
and activation of PS. These cascade reactions caused a significant
reduction in the tumor volume, demonstrating good antitumor potential.
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Uthaman, Saji; Kim, Yugyeong; Lee, Ji Young; Pillarisetti, Shameer; Huh, Kang Moo; Park, In-Kyu (2020). Self-Quenched
Polysaccharide Nanoparticles with a
Reactive Oxygen Species-Sensitive Cascade for Enhanced Photodynamic
Therapy. ACS Publications. Collection. https://doi.org/10.1021/acsami.0c06311
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AUTHORS (6)
SU
Saji Uthaman
YK
Yugyeong Kim
JL
Ji Young Lee
SP
Shameer Pillarisetti
KH
Kang Moo Huh
IP
In-Kyu Park
KEYWORDS
ROS-rich hypoxic coreself-quenched polysaccharide nanoparticlesphototoxic effectsGCreport novel TME-responsivelocoregional ROS levelstumor volumeROS-sensitive TK bond cleavagePStumor tissuereactive oxygen speciesnear-infrared irradiationcascade reactionsphotoactive formEnhanced Photodynamic Therapy Tumor microenvironmentself-quenching effectsNPs releaseTME conditionsSelf-Quenched Polysaccharide NanoparticlesReactive Oxygen Species-Sensitive CascadeROS-sensitive thioketalglycol chitosan