PMID- 33463352
OWN - NLM
STAT- MEDLINE
DCOM- 20210514
LR  - 20210514
IS  - 2373-9878 (Electronic)
IS  - 2373-9878 (Linking)
VI  - 6
IP  - 7
DP  - 2020 Jul 13
TI  - Ultrasound-Mediated Long-Circulating Nanopolymer Delivery of Therapeutic siRNA 
      and Antisense MicroRNAs Leads to Enhanced Paclitaxel Sensitivity in Epithelial 
      Ovarian Cancer Chemotherapy.
PG  - 4036-4050
LID - 10.1021/acsbiomaterials.0c00330 [doi]
AB  - Epithelial ovarian cancer (EOC) is one of the leading malignant tumors that 
      seriously threaten women's health. The development of new drugs or increasing the 
      sensitivities of current chemotherapy drugs is critically needed. The purpose of 
      this study was to assess the synergistic effects of two silencing RNAs 
      [salt-inducible kinase 2 (SIK2) siRNA and antisense-microRNA21 (anti-miR21)] 
      encapsulated in long-circulating folate-lipid-poly(lactic-co-glycolic acid) 
      (PLGA) hybrid nanopolymers (FaLPHNPs) administered using an ultrasound- and 
      microbubble (US-MB)-mediated approach to sensitize human EOC xenografts to 
      paclitaxel (PTX). In the in vitro assays, this lipid-PLGA hybrid nanopolymer 
      exhibited an extended circulation profile (t(1/2):  approximately 8.5 h); US-MB-mediated 
      complementary delivery of FaLPHNPs resulted in a significant reduction in EOC 
      cell (OVCR3, A2780, and SKOV3) proliferation. In vivo, there was a 2.5-fold 
      increase (p < 0.05) in RNA delivery in EOC xenografts, which resulted in a 
      notable inhibition of tumor growth compared with that in the 
      non-ultrasound-mediated and PTX alone-treated controls. We validated the 
      therapeutic roles of SIK2, the target gene in treating advanced ovarian cancer, 
      and anti-miR21 by evaluating the significant inhibition of tumor growth upon SIK2 
      silencing and inhibition of endogenous miR21 function. In summary, the results of 
      this study revealed that US-MB-mediated codelivery of SIK2 siRNA, and anti-miR21 
      encapsulated in a folate-lipid-PLGA hybrid polymer nanoparticle could 
      significantly improve the sensitivity of EOC tumors to PTX and is a highly 
      effective approach for treating EOC in complementary experiments. Further 
      research of this strategy could lead to better treatment results for patients 
      with EOC.
FAU - Liu, Yi
AU  - Liu Y
AD  - Department of Gynecology and Obstetrics, The Second Affiliated Hospital of 
      Chongqing Medical University, Chongqing 400010, China.
AD  - Institute of Ultrasound Imaging, The Second Affiliated Hospital of Chongqing 
      Medical University, Chongqing 400010, China.
FAU - Long, Tengfei
AU  - Long T
AD  - Department of Gynecology and Obstetrics, The Second Affiliated Hospital of 
      Chongqing Medical University, Chongqing 400010, China.
AD  - Institute of Ultrasound Imaging, The Second Affiliated Hospital of Chongqing 
      Medical University, Chongqing 400010, China.
FAU - Zhang, Ni
AU  - Zhang N
AD  - Institute of Ultrasound Imaging, The Second Affiliated Hospital of Chongqing 
      Medical University, Chongqing 400010, China.
AD  - Department of Oncology, The Second Affiliated Hospital of Chongqing Medical 
      University, Chongqing 400010, China.
FAU - Qiao, Bin
AU  - Qiao B
AD  - Institute of Ultrasound Imaging, The Second Affiliated Hospital of Chongqing 
      Medical University, Chongqing 400010, China.
FAU - Yang, Qiang
AU  - Yang Q
AD  - Institute of Ultrasound Imaging, The Second Affiliated Hospital of Chongqing 
      Medical University, Chongqing 400010, China.
AD  - Department of Neurosurgery, The Second Affiliated Hospital of Chongqing Medical 
      University, Chongqing 400010, China.
FAU - Luo, Yuanli
AU  - Luo Y
AD  - Institute of Ultrasound Imaging, The Second Affiliated Hospital of Chongqing 
      Medical University, Chongqing 400010, China.
FAU - Cao, Jin
AU  - Cao J
AD  - Institute of Ultrasound Imaging, The Second Affiliated Hospital of Chongqing 
      Medical University, Chongqing 400010, China.
FAU - Luo, Jing
AU  - Luo J
AD  - Department of Pathology, Chongqing Medical University, Chongqing 400010, China.
FAU - Yuan, Dong
AU  - Yuan D
AD  - Department of Gynecology and Obstetrics, The Second Affiliated Hospital of 
      Chongqing Medical University, Chongqing 400010, China.
FAU - Sun, Yixuan
AU  - Sun Y
AD  - Department of Gynecology and Obstetrics, The Second Affiliated Hospital of 
      Chongqing Medical University, Chongqing 400010, China.
FAU - Li, Yanxi
AU  - Li Y
AD  - Department of Reproductive Medicine Center, Daping Hospital, Army Medical 
      University (Third Military Medical University), Chongqing 400042, China.
FAU - Yang, Zhu
AU  - Yang Z
AUID- ORCID: 0000-0003-4096-5598
AD  - Department of Gynecology and Obstetrics, The Second Affiliated Hospital of 
      Chongqing Medical University, Chongqing 400010, China.
FAU - Wang, Z G
AU  - Wang ZG
AD  - Institute of Ultrasound Imaging, The Second Affiliated Hospital of Chongqing 
      Medical University, Chongqing 400010, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200603
PL  - United States
TA  - ACS Biomater Sci Eng
JT  - ACS biomaterials science & engineering
JID - 101654670
RN  - 0 (MIRN21 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (RNA, Small Interfering)
RN  - P88XT4IS4D (Paclitaxel)
SB  - IM
MH  - Carcinoma, Ovarian Epithelial/genetics
MH  - Cell Line, Tumor
MH  - Female
MH  - Humans
MH  - *MicroRNAs/genetics
MH  - *Ovarian Neoplasms/drug therapy
MH  - Paclitaxel/pharmacology
MH  - RNA, Small Interfering/genetics
OTO - NOTNLM
OT  - antisense-microRNA
OT  - epithelial ovarian cancer
OT  - lipid-PLGA hybrid nanopolymer
OT  - microbubble
OT  - paclitaxel chemosensitivity
OT  - siRNA
OT  - ultrasound
EDAT- 2021/01/20 06:00
MHDA- 2021/05/15 06:00
CRDT- 2021/01/19 08:40
PHST- 2021/01/19 08:40 [entrez]
PHST- 2021/01/20 06:00 [pubmed]
PHST- 2021/05/15 06:00 [medline]
AID - 10.1021/acsbiomaterials.0c00330 [doi]
PST - ppublish
SO  - ACS Biomater Sci Eng. 2020 Jul 13;6(7):4036-4050. doi: 
      10.1021/acsbiomaterials.0c00330. Epub 2020 Jun 3.