Preferential siRNA delivery to injured kidneys for combination treatment of acute kidney injury

Weimin Tang; Yi Chen; Hee Seong Jang; Yu Hang; Chinmay M. Jogdeo; Jing Li; Ling Ding; Chuhan Zhang; Ao Yu; Fei Yu; Kirk W. Foster; Babu J. Padanilam; David Oupický

doi:10.1016/j.jconrel.2021.11.029

Preferential siRNA delivery to injured kidneys for combination treatment of acute kidney injury

Weimin Tang, Yi Chen, Hee Seong Jang, Yu Hang, Chinmay M. Jogdeo, Jing Li, Ling Ding, Chuhan Zhang, Ao Yu, Fei Yu, Kirk W. Foster, Babu J. Padanilam, David Oupický

Research output: Contribution to journal › Article › peer-review

Abstract

Acute kidney injury (AKI) is characterized by a sudden loss of renal function and is associated with high morbidity and mortality. Tumor suppressor p53 and chemokine receptor CXCR4 were both implicated in the AKI pathology. Here, we report on the development and evaluation of polymeric CXCR4 antagonist (PCX) siRNA carrier for selective delivery to injured kidneys in AKI. Our results show that PCX/siRNA nanoparticles (polyplexes) provide protection against cisplatin injury to tubule cells in vitro when both CXCR4 and p53 are inhibited. The polyplexes selectively accumulate and are retained in the injured kidneys in cisplatin and bilateral ischemia reperfusion injury models of AKI. Treating AKI with the combined CXCR4 inhibition and p53 gene silencing with the PCX/sip53 polyplexes improves kidney function and decreases renal damage. Overall, our results suggest that the PCX/sip53 polyplexes have a significant potential to enhance renal accumulation in AKI and deliver therapeutic siRNA.

Original language	English (US)
Pages (from-to)	300-313
Number of pages	14
Journal	Journal of Controlled Release
Volume	341
DOIs	https://doi.org/10.1016/j.jconrel.2021.11.029
State	Published - Jan 2022
Externally published	Yes

Keywords

Acute kidney injury
CXCR4
Polyplexes
p53
siRNA, nanoparticles

ASJC Scopus subject areas

Pharmaceutical Science

Access to Document

10.1016/j.jconrel.2021.11.029

Cite this

@article{f5c7e46790c6400d83cbdce71da227f4,

title = "Preferential siRNA delivery to injured kidneys for combination treatment of acute kidney injury",

abstract = "Acute kidney injury (AKI) is characterized by a sudden loss of renal function and is associated with high morbidity and mortality. Tumor suppressor p53 and chemokine receptor CXCR4 were both implicated in the AKI pathology. Here, we report on the development and evaluation of polymeric CXCR4 antagonist (PCX) siRNA carrier for selective delivery to injured kidneys in AKI. Our results show that PCX/siRNA nanoparticles (polyplexes) provide protection against cisplatin injury to tubule cells in vitro when both CXCR4 and p53 are inhibited. The polyplexes selectively accumulate and are retained in the injured kidneys in cisplatin and bilateral ischemia reperfusion injury models of AKI. Treating AKI with the combined CXCR4 inhibition and p53 gene silencing with the PCX/sip53 polyplexes improves kidney function and decreases renal damage. Overall, our results suggest that the PCX/sip53 polyplexes have a significant potential to enhance renal accumulation in AKI and deliver therapeutic siRNA.",

keywords = "Acute kidney injury, CXCR4, Polyplexes, p53, siRNA, nanoparticles",

author = "Weimin Tang and Yi Chen and Jang, {Hee Seong} and Yu Hang and Jogdeo, {Chinmay M.} and Jing Li and Ling Ding and Chuhan Zhang and Ao Yu and Fei Yu and Foster, {Kirk W.} and Padanilam, {Babu J.} and David Oupick{\'y}",

note = "Publisher Copyright: {\textcopyright} 2021 Elsevier B.V.",

year = "2022",

month = jan,

doi = "10.1016/j.jconrel.2021.11.029",

language = "English (US)",

volume = "341",

pages = "300--313",

journal = "Journal of Controlled Release",

issn = "0168-3659",

publisher = "Elsevier",

}

TY - JOUR

T1 - Preferential siRNA delivery to injured kidneys for combination treatment of acute kidney injury

AU - Tang, Weimin

AU - Chen, Yi

AU - Jang, Hee Seong

AU - Hang, Yu

AU - Jogdeo, Chinmay M.

AU - Li, Jing

AU - Ding, Ling

AU - Zhang, Chuhan

AU - Yu, Ao

AU - Yu, Fei

AU - Foster, Kirk W.

AU - Padanilam, Babu J.

AU - Oupický, David

PY - 2022/1

Y1 - 2022/1

N2 - Acute kidney injury (AKI) is characterized by a sudden loss of renal function and is associated with high morbidity and mortality. Tumor suppressor p53 and chemokine receptor CXCR4 were both implicated in the AKI pathology. Here, we report on the development and evaluation of polymeric CXCR4 antagonist (PCX) siRNA carrier for selective delivery to injured kidneys in AKI. Our results show that PCX/siRNA nanoparticles (polyplexes) provide protection against cisplatin injury to tubule cells in vitro when both CXCR4 and p53 are inhibited. The polyplexes selectively accumulate and are retained in the injured kidneys in cisplatin and bilateral ischemia reperfusion injury models of AKI. Treating AKI with the combined CXCR4 inhibition and p53 gene silencing with the PCX/sip53 polyplexes improves kidney function and decreases renal damage. Overall, our results suggest that the PCX/sip53 polyplexes have a significant potential to enhance renal accumulation in AKI and deliver therapeutic siRNA.

AB - Acute kidney injury (AKI) is characterized by a sudden loss of renal function and is associated with high morbidity and mortality. Tumor suppressor p53 and chemokine receptor CXCR4 were both implicated in the AKI pathology. Here, we report on the development and evaluation of polymeric CXCR4 antagonist (PCX) siRNA carrier for selective delivery to injured kidneys in AKI. Our results show that PCX/siRNA nanoparticles (polyplexes) provide protection against cisplatin injury to tubule cells in vitro when both CXCR4 and p53 are inhibited. The polyplexes selectively accumulate and are retained in the injured kidneys in cisplatin and bilateral ischemia reperfusion injury models of AKI. Treating AKI with the combined CXCR4 inhibition and p53 gene silencing with the PCX/sip53 polyplexes improves kidney function and decreases renal damage. Overall, our results suggest that the PCX/sip53 polyplexes have a significant potential to enhance renal accumulation in AKI and deliver therapeutic siRNA.

KW - Acute kidney injury

KW - CXCR4

KW - Polyplexes

KW - p53

KW - siRNA, nanoparticles

UR - http://www.scopus.com/inward/record.url?scp=85119999049&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85119999049&partnerID=8YFLogxK

U2 - 10.1016/j.jconrel.2021.11.029

DO - 10.1016/j.jconrel.2021.11.029

M3 - Article

C2 - 34826532

AN - SCOPUS:85119999049

SN - 0168-3659

VL - 341

SP - 300

EP - 313

JO - Journal of Controlled Release

JF - Journal of Controlled Release

ER -

Preferential siRNA delivery to injured kidneys for combination treatment of acute kidney injury

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this