Intracellularly Activatable Nanovasodilators To Enhance
Passive Cancer Targeting Regime
Posted on 2018-03-08 - 20:34
Conventional cancer targeting with
nanoparticles has been based
on the assumed enhanced permeability and retention (EPR) effect. The
data obtained in clinical trials to date, however, have rarely supported
the presence of such an effect. To address this challenge, we formulated
intracellular nitric oxide-generating nanoparticles (NO-NPs) for the
tumor site-specific delivery of NO, a well-known vasodilator, with
the intention of boosting EPR. These nanoparticles are self-assembled
under aqueous conditions from amphiphilic copolymers of poly(ethylene
glycol) and nitrated dextran, which possesses inherent NO release
properties in the reductive environment of cancer cells. After systemic
administration of the NO-NPs, we quantitatively assessed and visualized
increased tumor blood flow as well as enhanced vascular permeability
than could be achieved without NO. Additionally, we prepared doxorubicin
(DOX)-encapsulated NO-NPs and demonstrated consequential improvement
in therapeutic efficacy over the control groups with considerably
improved DOX intratumoral accumulation. Overall, this proof of concept
study implies a high potency of the NO-NPs as an EPR enhancer to achieve
better clinical outcomes.
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Deepagan, V. G.; Ko, Hyewon; Kwon, Seunglee; Rao, N. Vijayakameswara; Kim, Sang Kyoon; Um, Wooram; et al. (2018). Intracellularly Activatable Nanovasodilators To Enhance
Passive Cancer Targeting Regime. ACS Publications. Collection. https://doi.org/10.1021/acs.nanolett.8b00495
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AUTHORS (13)
VD
V. G. Deepagan
HK
Hyewon Ko
SK
Seunglee Kwon
NR
N. Vijayakameswara Rao
SK
Sang Kyoon Kim
WU
Wooram Um
SL
Sohee Lee
JM
Jiwoong Min
JL
Jeongjin Lee
KC
Ki Young Choi
SS
Sol Shin
MS
Minah Suh
JP
Jae Hyung Park
KEYWORDS
amphiphilic copolymerscancer cellspermeabilityDOX intratumoral accumulationrelease propertiesEPR enhancerintracellular nitric oxide-generating nanoparticlesIntracellularly Activatable NanovasodilatorsNO-NPconcept studycontrol groupsEnhance Passive Cancer Targeting Regimetumor blood flowreductive environmenttumor site-specific deliverynitrated dextran