PMID- 31442373
OWN - NLM
STAT- MEDLINE
DCOM- 20200422
LR  - 20200930
IS  - 1530-6992 (Electronic)
IS  - 1530-6984 (Linking)
VI  - 19
IP  - 9
DP  - 2019 Sep 11
TI  - Octopus-like Flexible Vector for Noninvasive Intraocular Delivery of Short 
      Interfering Nucleic Acids.
PG  - 6410-6417
LID - 10.1021/acs.nanolett.9b02596 [doi]
AB  - Gene therapy is promising for chronic posterior ocular diseases, which are causal 
      factors for severe vision impairment and even blindness worldwide. However, the 
      inherent absorption barriers of the eye restrict intraocular delivery of 
      therapeutic nucleic acids via topical instillation. Safe and efficient nonviral 
      vectors for ocular gene therapy are still unmet clinical desires. Herein, an 
      octopus-like flexible multivalent penetratin (MVP) was designed to facilitate 
      condensation and delivery of therapeutic nucleic acids using multiarm 
      polyethylene glycol (PEG) as a core and conjugating penetratin at each end of the 
      PEG arms as outspread tentacles. Among the MVPs, 8-valent penetratin (8VP) stably 
      compacted nucleic acids into positively charged polyplexes smaller than 100 nm, 
      promoting cellular uptake efficiency (approaching 100%) and transfection rate 
      (over 75%). After being instilled into the conjunctival sac, 8VP enabled rapid 
      (<10 min) and prolonged (>6 h) distribution of nucleic acids in the retina via a 
      noncorneal pathway. In a retinoblastoma-bearing mice model, topical instillation 
      of 8VP/siRNA efficiently inhibited the protein expression of intraocular tumor 
      without toxicity. MVP is advantageous over the commercial transfection reagent in 
      safety and efficiency, and therefore provides a promising vector for noninvasive 
      intraocular gene delivery.
FAU - Jiang, Kuan
AU  - Jiang K
AD  - Key Laboratory of Smart Drug Delivery, Ministry of Education; Department of 
      Pharmaceutics, School of Pharmacy , Fudan University , Shanghai 201203 , China.
FAU - Hu, Yang
AU  - Hu Y
AD  - Key Laboratory of Smart Drug Delivery, Ministry of Education; Department of 
      Pharmaceutics, School of Pharmacy , Fudan University , Shanghai 201203 , China.
FAU - Gao, Xin
AU  - Gao X
AD  - Key Laboratory of Smart Drug Delivery, Ministry of Education; Department of 
      Pharmaceutics, School of Pharmacy , Fudan University , Shanghai 201203 , China.
FAU - Zhan, Changyou
AU  - Zhan C
AD  - Key Laboratory of Smart Drug Delivery, Ministry of Education; Department of 
      Pharmaceutics, School of Pharmacy , Fudan University , Shanghai 201203 , China.
AD  - Department of Pharmacology, School of Basic Medical Sciences , Fudan University , 
      Shanghai 200032 , China.
FAU - Zhang, Yanyu
AU  - Zhang Y
AD  - Key Laboratory of Smart Drug Delivery, Ministry of Education; Department of 
      Pharmaceutics, School of Pharmacy , Fudan University , Shanghai 201203 , China.
FAU - Yao, Shengyu
AU  - Yao S
AD  - Key Laboratory of Smart Drug Delivery, Ministry of Education; Department of 
      Pharmaceutics, School of Pharmacy , Fudan University , Shanghai 201203 , China.
FAU - Xie, Cao
AU  - Xie C
AD  - Key Laboratory of Smart Drug Delivery, Ministry of Education; Department of 
      Pharmaceutics, School of Pharmacy , Fudan University , Shanghai 201203 , China.
FAU - Wei, Gang
AU  - Wei G
AUID- ORCID: 0000-0002-9600-0982
AD  - Key Laboratory of Smart Drug Delivery, Ministry of Education; Department of 
      Pharmaceutics, School of Pharmacy , Fudan University , Shanghai 201203 , China.
FAU - Lu, Weiyue
AU  - Lu W
AUID- ORCID: 0000-0001-8003-2675
AD  - Key Laboratory of Smart Drug Delivery, Ministry of Education; Department of 
      Pharmaceutics, School of Pharmacy , Fudan University , Shanghai 201203 , China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190827
PL  - United States
TA  - Nano Lett
JT  - Nano letters
JID - 101088070
RN  - 0 (Cell-Penetrating Peptides)
RN  - 0 (RNA, Small Interfering)
RN  - A2AQZ20TEK (penetratin)
SB  - IM
MH  - Animals
MH  - Cell Line, Tumor
MH  - *Cell-Penetrating Peptides/chemistry/pharmacokinetics/pharmacology
MH  - Conjunctiva/*metabolism/pathology
MH  - *Eye Neoplasms/genetics/metabolism/pathology/therapy
MH  - *Genetic Therapy
MH  - Humans
MH  - Injections, Intraocular
MH  - Mice
MH  - *RNA, Small Interfering/chemistry/genetics/pharmacokinetics/pharmacology
MH  - *Retinoblastoma/genetics/metabolism/pathology/therapy
MH  - *Transfection
OTO - NOTNLM
OT  - Posterior ocular diseases
OT  - gene delivery
OT  - noncorneal pathway
OT  - penetratin
OT  - topical instillation
EDAT- 2019/08/24 06:00
MHDA- 2020/04/23 06:00
CRDT- 2019/08/24 06:00
PHST- 2019/08/24 06:00 [pubmed]
PHST- 2020/04/23 06:00 [medline]
PHST- 2019/08/24 06:00 [entrez]
AID - 10.1021/acs.nanolett.9b02596 [doi]
PST - ppublish
SO  - Nano Lett. 2019 Sep 11;19(9):6410-6417. doi: 10.1021/acs.nanolett.9b02596. Epub 
      2019 Aug 27.