PMID- 22830501
OWN - NLM
STAT- MEDLINE
DCOM- 20130521
LR  - 20121219
IS  - 1748-6963 (Electronic)
IS  - 1743-5889 (Linking)
VI  - 7
IP  - 12
DP  - 2012 Dec
TI  - Efficient systemic delivery of siRNA by using high-density lipoprotein-mimicking 
      peptide lipid nanoparticles.
PG  - 1813-25
LID - 10.2217/nnm.12.73 [doi]
AB  - The main challenge for RNAi therapeutics lies in systemic delivery of siRNA to 
      the correct tissues and transporting them into the cytoplasm of targeted cells, 
      at safe, therapeutic levels. Recently, we developed a high-density 
      lipoprotein-mimicking peptide-phospholipid scaffold (HPPS) and demonstrated its 
      direct cytosolic delivery of siRNA in vitro, thereby bypassing endosomal 
      trapping. AIM: We investigate the in vivo implementation of HPPS for siRNA 
      delivery. METHOD & RESULTS: After systemic administration in KB tumor-bearing 
      mice, HPPS prolonged the blood circulation time of cholesterol-modified siRNA 
      (chol-siRNA) by a factor of four, improved its biodistribution and facilitated 
      its uptake in scavenger receptor class B type I overexpressed tumors. For 
      therapeutic targeting to the bcl-2 gene, the HPPS-chol-si-bcl-2 nanoparticles 
      downregulated Bcl-2 protein, induced enhanced apoptosis (2.5-fold) in tumors when 
      compared with controls (saline, HPPS, HPPS-chol-si-scramble and chol-si-bcl-2) 
      and significantly inhibited tumor growth with no adverse effect. CONCLUSION: HPPS 
      is a safe, efficient nanocarrier for RNAi therapeutics in vivo.
FAU - Lin, Qiaoya
AU  - Lin Q
AD  - Ontario Cancer Institute & Techna Institute, University Health Network, Toronto, 
      ON, Canada.
FAU - Chen, Juan
AU  - Chen J
FAU - Jin, Honglin
AU  - Jin H
FAU - Ng, Kenneth K
AU  - Ng KK
FAU - Yang, Mi
AU  - Yang M
FAU - Cao, Weiguo
AU  - Cao W
FAU - Ding, Lili
AU  - Ding L
FAU - Zhang, Zhihong
AU  - Zhang Z
FAU - Zheng, Gang
AU  - Zheng G
LA  - eng
GR  - CCI-102936/Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120726
PL  - England
TA  - Nanomedicine (Lond)
JT  - Nanomedicine (London, England)
JID - 101278111
RN  - 0 (Lipoproteins, HDL)
RN  - 0 (Peptides)
RN  - 0 (Phospholipids)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (RNA, Small Interfering)
SB  - IM
MH  - Animals
MH  - Biomimetic Materials/adverse effects/*chemistry
MH  - Genes, bcl-2
MH  - Genetic Therapy
MH  - Lipoproteins, HDL/adverse effects/*chemistry
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Nude
MH  - Nanoparticles/adverse effects/*chemistry
MH  - Neoplasms/genetics/pathology/*therapy
MH  - Peptides/adverse effects/*chemistry
MH  - Phospholipids/adverse effects/*chemistry
MH  - Proto-Oncogene Proteins c-bcl-2/genetics
MH  - RNA Interference
MH  - RNA, Small Interfering/*administration & dosage/genetics/therapeutic use
MH  - Xenograft Model Antitumor Assays
EDAT- 2012/07/27 06:00
MHDA- 2013/05/23 06:00
CRDT- 2012/07/27 06:00
PHST- 2012/07/27 06:00 [entrez]
PHST- 2012/07/27 06:00 [pubmed]
PHST- 2013/05/23 06:00 [medline]
AID - 10.2217/nnm.12.73 [doi]
PST - ppublish
SO  - Nanomedicine (Lond). 2012 Dec;7(12):1813-25. doi: 10.2217/nnm.12.73. Epub 2012 
      Jul 26.