PMID- 29601972
OWN - NLM
STAT- MEDLINE
DCOM- 20180924
LR  - 20190610
IS  - 1873-3476 (Electronic)
IS  - 0378-5173 (Print)
IS  - 0378-5173 (Linking)
VI  - 543
IP  - 1-2
DP  - 2018 May 30
TI  - Complexation of Chol-DsiRNA in place of Chol-siRNA greatly increases the duration 
      of mRNA suppression by polyplexes of PLL(30)-PEG(5K) in primary murine syngeneic 
      breast tumors after i.v. administration.
PG  - 130-138
LID - S0378-5173(18)30192-3 [pii]
LID - 10.1016/j.ijpharm.2018.03.045 [doi]
AB  - RNA interference has tremendous potential for cancer therapy but is limited by 
      the insufficient potency of RNAi molecules after i.v. administration. We 
      previously found that complexation with PLL(30)-PEG(5K) greatly increases the 
      potency of 3'-cholesterol-modified siRNA [Chol-siRNA] in primary murine syngeneic 
      4T1 breast tumors after i.v. administration but mRNA suppression decreases 24 h 
      after the final dose. We hypothesized that complexation of cholesterol-modified 
      Dicer-substrate siRNA (Chol-DsiRNA) in place of Chol-siRNA can increase the 
      potency and duration of suppression by polyplexes of PLL(30)-PEG(5K) in solid 
      tumors. We found that replacing Chol-siRNA with Chol-DsiRNA increased polyplex 
      loading and nuclease protection, suppressed stably expressed luciferase to the 
      same extent in primary murine 4T1-Luc breast tumors under the current dosage 
      regimen, but maintained suppression ~72 h after the final dose. The kinetics of 
      suppression in 4T1-Luc over 72 h, however, were similar between DsiLuc and siLuc 
      after electroporation and between polyplexes of Chol-DsiLuc and Chol-siLuc after 
      transfection, suggesting that Chol-DsiRNA polyplexes increase the duration of 
      mRNA suppression through differences in polyplex activities in vivo. Thus, 
      replacing Chol-siRNA with Chol-DsiRNA may significantly increase the duration of 
      mRNA suppression by polyplexes of PLL(30)-PEG(5K) and possibly other PEGylated 
      polycationic polymers in primary tumors and metastases after i.v. administration.
CI  - Copyright (c) 2018 Elsevier B.V. All rights reserved.
FAU - Ambardekar, Vishakha V
AU  - Ambardekar VV
AD  - Lupin Ltd, 46/47, A, Village Nande, Taluka Mulshi Dist, Pune 412 115, India(1).
FAU - Wakaskar, Rajesh R
AU  - Wakaskar RR
AD  - INSYS Therapeutics, 444 S Ellis St and 410 S Benson Ln, Chandler, AZ 85224, 
      USA(1).
FAU - Ye, Zhen
AU  - Ye Z
AD  - Department of Pharmaceutical Sciences, College of Pharmacy, University of 
      Nebraska Medical Center, Omaha, NE 68198-6025, USA.
FAU - Curran, Stephen M
AU  - Curran SM
AD  - Department of Pharmaceutical Sciences, College of Pharmacy, University of 
      Nebraska Medical Center, Omaha, NE 68198-6025, USA.
FAU - McGuire, Timothy R
AU  - McGuire TR
AD  - Department of Pharmacy Practice, College of Pharmacy, University of Nebraska 
      Medical Center, Omaha, NE 68198-6025, USA.
FAU - Coulter, Don W
AU  - Coulter DW
AD  - Department of Pediatrics, Division of Pediatric Hematology/Oncology, Department 
      of Radiation Oncology, J. Bruce Henriksen Cancer Research Laboratories, 
      University of Nebraska Medical Center, Omaha, NE 68198-2168, USA.
FAU - Singh, Rakesh K
AU  - Singh RK
AD  - Center for Drug Delivery and Nanomedicine, College of Pharmacy, University of 
      Nebraska Medical Center, Omaha, NE 68198-6025, USA; Department of Pathology and 
      Microbiology, University of Nebraska Medical Center, Omaha, NE 68198-5900, USA.
FAU - Vetro, Joseph A
AU  - Vetro JA
AD  - Center for Drug Delivery and Nanomedicine, College of Pharmacy, University of 
      Nebraska Medical Center, Omaha, NE 68198-6025, USA; Department of Pharmaceutical 
      Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 
      68198-6025, USA. Electronic address: jvetro@unmc.edu.
LA  - eng
GR  - P20 GM103480/GM/NIGMS NIH HHS/United States
GR  - P20 RR021937/RR/NCRR NIH HHS/United States
GR  - P30 CA036727/CA/NCI NIH HHS/United States
GR  - R41 TR001902/TR/NCATS NIH HHS/United States
PT  - Journal Article
DEP - 20180327
PL  - Netherlands
TA  - Int J Pharm
JT  - International journal of pharmaceutics
JID - 7804127
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (polylysine-graft-(poly(ethylene glycol)))
RN  - 25104-18-1 (Polylysine)
RN  - 3WJQ0SDW1A (Polyethylene Glycols)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - EC 1.13.12.- (Luciferases)
RN  - EC 3.1.26.3 (Dicer1 protein, mouse)
RN  - EC 3.1.26.3 (Ribonuclease III)
RN  - EC 3.6.4.13 (DEAD-box RNA Helicases)
SB  - IM
MH  - Administration, Intravenous
MH  - Animals
MH  - Cell Line, Tumor
MH  - Cholesterol/administration & dosage/*chemistry
MH  - *DEAD-box RNA Helicases
MH  - Female
MH  - Luciferases/genetics
MH  - Mammary Neoplasms, Experimental/*genetics
MH  - Mice, Inbred BALB C
MH  - Polyethylene Glycols/administration & dosage/*chemistry
MH  - Polylysine/administration & dosage/*analogs & derivatives/chemistry
MH  - RNA, Messenger
MH  - RNA, Small Interfering/administration & dosage/*chemistry
MH  - *Ribonuclease III
PMC - PMC5927825
MID - NIHMS957440
OTO - NOTNLM
OT  - Chol-DsiRNA polymer micelles
OT  - Chol-DsiRNA polyplexes
OT  - Chol-siRNA polymer micelles
OT  - Chol-siRNA polyplexes
OT  - Drug delivery
OT  - DsiRNA
OT  - RNA interference
EDAT- 2018/03/31 06:00
MHDA- 2018/09/25 06:00
PMCR- 2019/05/30
CRDT- 2018/03/31 06:00
PHST- 2017/11/05 00:00 [received]
PHST- 2018/01/25 00:00 [revised]
PHST- 2018/03/24 00:00 [accepted]
PHST- 2018/03/31 06:00 [pubmed]
PHST- 2018/09/25 06:00 [medline]
PHST- 2018/03/31 06:00 [entrez]
PHST- 2019/05/30 00:00 [pmc-release]
AID - S0378-5173(18)30192-3 [pii]
AID - 10.1016/j.ijpharm.2018.03.045 [doi]
PST - ppublish
SO  - Int J Pharm. 2018 May 30;543(1-2):130-138. doi: 10.1016/j.ijpharm.2018.03.045. 
      Epub 2018 Mar 27.