Nanomedicine (Lond.) (Epub ahead of print) ISSN 1743-5889
part of
Research Article
10.2217/nnm-2017-0256 © 2017 Future Medicine Ltd
Aim: We used resveratrol (Res)-loaded nanoparticles (Res NPs) as a novel method
for improving the pharmacokinetic properties of Res and analyzed the effect of Res
NPs in chronic kidney disease (CKD). Materials & methods: We coupled anti-kidney
injury molecule-1 antibodies to Res NPs and analyzed safety and efficacy. Results:
Res NPs had low toxicity and induced autophagy. Res NPs inhibited the NLRP3
inflammasome and IL-1β secretion. Higher NLRP3 expression levels were observed in
peripheral blood monocytic cells of CKD patients than healthy individuals. Treatment
with kidney injury molecule-1-Res NPs significantly reduced creatinine and protected
against tubulointerstitial injury in a murine model of CKD. Conclusion: Res NPs
through NLRP3 inflammasome attenuation and autophagy induction may be as a
strategy to prevent CKD.
First draft submitted: 14 August 2017; Accepted for publication: 31 August 2017;
Published online: 8 September 2017
Keywords: autophagy•chronickidneydisease•infammasome•kidneyinjurymolecule-1
•resveratrol
Chronic kidney disease (CKD) is a progres-
sive and irreversible loss of renal function
characterized by a decreased glomerular fil-
tration rate. CKD is becoming one of the
most important health problems worldwide
and greatly affects patients’ quality of life [1,2] .
Rates of CKD in the population are increas-
ing, largely because of increasing prevalence
of associated comorbidities such as cardio-
vascular disease, diabetes, hypertension and
obesity. Furthermore, untreated CKD can
result in end-stage renal disease and neces-
sitate dialysis or kidney transplantation [3] . In
CKD, several features might contribute to a
persistent state of inflammation and its pro-
oxidant effects, such as proteinuria, reduced
cytokine clearance and infections [4] . Patients
with CKD demonstrate antioxidant defense
deficiency because of the reduced consump-
tion of vitamins and minerals containing
antioxidants [5] . Therefore, chronic inflam-
mation and oxidative stress features play a
key role in the development and progression
of CKD and related disorders [6] . Based on
previous studies, kidney injury molecule-1
(KIM-1), a recently discovered transmem-
brane protein with extracellular mucin and
immunoglobulin domains, is believed to play
a role in tubulointerstitial damage [7] . KIM-1
is not detectable in normal human or rodent
kidneys but KIM-1 expression is increased
more than that of any other protein in injured
kidneys, and it is localized predominantly to
the apical membrane of surviving proximal
epithelial cells [7,8] . Therefore, upregulation
of renal KIM-1 expression is located in dedif-
ferentiated proximal tubular cells and is asso-
ciated with fibrosis and inflammation [9,10] .
The incidence of CKD has increased dramat-
ically over the past 10 years, and new strate-
gies for slowing its progression are urgently
needed [2] .
Accumulated evidence has revealed that
persistent inflammation leads to progressive
Resveratrol-loaded nanoparticles
conjugated with kidney injury molecule-1
as a drug delivery system for potential use
in chronic kidney disease
Yuh-Feng Lin
‡,1,2
, Yu-Hsuan
Lee
3
, Yung-Ho Hsu
1,4
, Yi-
Jie Chen
1
, Yuan-Feng Lin
2
,
Fong-Yu Cheng
‡,5
& Hui-Wen
Chiu*
,1,2
1
DivisionofNephrology,Departmentof
InternalMedicine,ShuangHoHospital,
TaipeiMedicalUniversity,Taiwan
2
GraduateInstituteofClinicalMedicine,
CollegeofMedicine,TaipeiMedical
University,Taipei,Taiwan
3
DepartmentofFoodSafety/Hygiene&
RiskManagement,CollegeofMedicine,
NationalChengKungUniversity,Tainan,
Taiwan
4
DepartmentofInternalMedicine,
SchoolofMedicine,CollegeofMedicine,
TaipeiMedicalUniversity,Taipei,Taiwan
5
DepartmentofChemistry,Chinese
CultureUniversity,Taipei,Taiwan
*Authorforcorrespondence:
Tel.:+886222490088ext.8884
leu3@tmu.edu.tw
‡
Authorscontributedequally
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