PMID- 35076584
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220205
IS  - 2311-553X (Electronic)
IS  - 2311-553X (Linking)
VI  - 8
IP  - 1
DP  - 2022 Jan 13
TI  - Direct Comparison of Chol-siRNA Polyplexes and Chol-DsiRNA Polyplexes Targeting 
      STAT3 in a Syngeneic Murine Model of TNBC.
LID - 10.3390/ncrna8010008 [doi]
LID - 8
AB  - RNA interference (RNAi) molecules have tremendous potential for cancer therapy 
      but are limited by insufficient potency after intravenous (IV) administration. We 
      previously found that polymer complexes (polyplexes) formed between 
      3'-cholesterol-modified siRNA (Chol-siRNA) or DsiRNA (Chol-DsiRNA) and the 
      cationic diblock copolymer PLL[30]-PEG[5K] greatly increase RNAi potency against 
      stably expressed LUC mRNA in primary syngeneic murine breast tumors after daily 
      IV dosing. Chol-DsiRNA polyplexes, however, maintain LUC mRNA suppression for ~48 
      h longer after the final dose than Chol-siRNA polyplexes, which suggests that 
      they are the better candidate formulation. Here, we directly compared the 
      activities of Chol-siRNA polyplexes and Chol-DsiRNA polyplexes in primary murine 
      4T1 breast tumors against STAT3, a therapeutically relevant target gene that is 
      overexpressed in many solid tumors, including breast cancer. We found that 
      Chol-siSTAT3 polyplexes suppressed STAT3 mRNA in 4T1 tumors with similar potency 
      (half-maximal ED(50) 0.3 mg/kg) and kinetics (over 96 h) as Chol-DsiSTAT3 
      polyplexes, but with slightly lower activity against total Stat3 protein (29% vs. 
      42% suppression) and tumor growth (11.5% vs. 8.6% rate-based T/C ratio) after 
      repeated IV administration of equimolar, tumor-saturating doses every other day. 
      Thus, both Chol-siRNA polyplexes and Chol-DsiRNA polyplexes may be suitable 
      clinical candidates for the RNAi therapy of breast cancer and other solid tumors.
FAU - Ye, Zhen
AU  - Ye Z
AD  - Department of Pharmaceutical Sciences, College of Pharmacy, University of 
      Nebraska Medical Center, Omaha, NE 68198, USA.
FAU - Abdelmoaty, Mai Mohamed
AU  - Abdelmoaty MM
AUID- ORCID: 0000-0001-7672-7052
AD  - Department of Pharmaceutical Sciences, College of Pharmacy, University of 
      Nebraska Medical Center, Omaha, NE 68198, USA.
AD  - Therapeutic Chemistry Department, Pharmaceutical and Drug Industries Research 
      Division, National Research Centre, Giza 12622, Egypt.
FAU - Curran, Stephen M
AU  - Curran SM
AD  - Department of Pharmaceutical Sciences, College of Pharmacy, University of 
      Nebraska Medical Center, Omaha, NE 68198, USA.
FAU - Dyavar, Shetty Ravi
AU  - Dyavar SR
AD  - Department of Pharmacy Practice, College of Pharmacy, University of Nebraska 
      Medical Center, Omaha, NE 68198, USA.
FAU - Kumar, Devendra
AU  - Kumar D
AD  - Department of Pharmaceutical Sciences, College of Pharmacy, University of 
      Nebraska Medical Center, Omaha, NE 68198, USA.
FAU - Alnouti, Yazen
AU  - Alnouti Y
AD  - Department of Pharmaceutical Sciences, College of Pharmacy, University of 
      Nebraska Medical Center, Omaha, NE 68198, USA.
AD  - Center for Drug Delivery and Nanomedicine, University of Nebraska Medical Center, 
      Omaha, NE 68198, USA.
FAU - Coulter, Don W
AU  - Coulter DW
AD  - Department of Pediatrics, Division of Pediatric Hematology/Oncology, University 
      of Nebraska Medical Center, Omaha, NE 68198, USA.
FAU - Podany, Anthony T
AU  - Podany AT
AD  - Department of Pharmacy Practice, College of Pharmacy, University of Nebraska 
      Medical Center, Omaha, NE 68198, USA.
FAU - Singh, Rakesh K
AU  - Singh RK
AUID- ORCID: 0000-0002-1317-3520
AD  - Center for Drug Delivery and Nanomedicine, University of Nebraska Medical Center, 
      Omaha, NE 68198, USA.
AD  - Department of Pathology and Microbiology, University of Nebraska Medical Center, 
      Omaha, NE 68198, USA.
FAU - Vetro, Joseph A
AU  - Vetro JA
AUID- ORCID: 0000-0003-2446-9797
AD  - Department of Pharmaceutical Sciences, College of Pharmacy, University of 
      Nebraska Medical Center, Omaha, NE 68198, USA.
AD  - Center for Drug Delivery and Nanomedicine, University of Nebraska Medical Center, 
      Omaha, NE 68198, USA.
LA  - eng
GR  - 1R41TR001902-01A1/NH/NIH HHS/United States
GR  - LB 417/State of Nebraska/
GR  - R01 CA228524/CA/NCI NIH HHS/United States
GR  - R41 TR001902/TR/NCATS NIH HHS/United States
GR  - P30CA03672/NH/NIH HHS/United States
GR  - P30 CA036727/CA/NCI NIH HHS/United States
GR  - R01CA228524/NH/NIH HHS/United States
PT  - Journal Article
DEP - 20220113
PL  - Switzerland
TA  - Noncoding RNA
JT  - Non-coding RNA
JID - 101652294
PMC - PMC8788547
OTO - NOTNLM
OT  - Chol-DsiRNA polymer micelles
OT  - Chol-siRNA polymer micelles
OT  - DsiRNA delivery
OT  - RNAi
OT  - RNAi delivery
OT  - drug delivery
OT  - siRNA delivery
COIS- J.A.V. is cofounder of a company that licenses the described technology.
EDAT- 2022/01/26 06:00
MHDA- 2022/01/26 06:01
PMCR- 2022/01/13
CRDT- 2022/01/25 12:19
PHST- 2021/09/10 00:00 [received]
PHST- 2022/01/06 00:00 [revised]
PHST- 2022/01/10 00:00 [accepted]
PHST- 2022/01/25 12:19 [entrez]
PHST- 2022/01/26 06:00 [pubmed]
PHST- 2022/01/26 06:01 [medline]
PHST- 2022/01/13 00:00 [pmc-release]
AID - ncrna8010008 [pii]
AID - ncrna-08-00008 [pii]
AID - 10.3390/ncrna8010008 [doi]
PST - epublish
SO  - Noncoding RNA. 2022 Jan 13;8(1):8. doi: 10.3390/ncrna8010008.