PMID- 28453254
OWN - NLM
STAT- MEDLINE
DCOM- 20180315
LR  - 20181202
IS  - 1526-4602 (Electronic)
IS  - 1525-7797 (Linking)
VI  - 18
IP  - 6
DP  - 2017 Jun 12
TI  - Gene Transfection Mediated by Catiomers Requires Free Highly Charged Polymer 
      Chains To Overcome Intracellular Barriers.
PG  - 1918-1927
LID - 10.1021/acs.biomac.7b00344 [doi]
AB  - The prospective use of the block copolymers poly(ethylene 
      oxide)(113)-b-poly[2-(diethylamino)ethyl methacrylate](50) (PEO(113)-b-PDEA(50)) 
      and poly[oligo(ethylene glycol)methyl ether 
      methacrylate](70)-b-poly[oligo(ethylene glycol)methyl ether 
      methacrylate(10)-co-2-(diethylamino)ethyl 
      methacrylate(47)-co-2-(diisopropylamino)ethyl methacrylate(47)] 
      (POEGMA(70)-b-P(OEGMA(10)-co-DEA(47)-co-DPA(47))) as nonviral gene vectors was 
      evaluated. The polymers are able to properly condense DNA into nanosized 
      particles (R(H)  approximately  75 nm), which are marginally cytotoxic and can be uptaken by 
      cells. However, the green fluorescent protein (GFP) expression assays evidenced 
      that DNA delivery is essentially negligible meaning that intracellular 
      trafficking hampers efficient gene release. Subsequently, we demonstrate that 
      cellular uptake and particularly the quantity of GFP-positive cells are 
      substantially enhanced when the block copolymer polyplexes are produced and 
      further supplemented by BPEI chains (branched polyethylenimine). The dynamic 
      light scattering/electrophoretic light scattering/isothermal titration 
      calorimetry data suggest that such a strategy allows the adsorption of BPEI onto 
      the surface of the polyplexes, and this phenomenon is responsible for increasing 
      the size and surface charge of the assemblies. Nevertheless, most of the BPEI 
      chains remain freely diffusing in the systems. The biological assays confirmed 
      that cellular uptake is enhanced in the presence of BPEI and principally, the 
      free highly charged polymer chains play the central role in intracellular 
      trafficking and gene transfection. These investigations pointed out that the 
      transfection efficiency versus cytotoxicity issue can be balanced by a mixture of 
      BPEI and less cytotoxic agents such as for instance the proposed block 
      copolymers.
FAU - Albuquerque, Lindomar J C
AU  - Albuquerque LJC
AD  - Centro de Ciencias Naturais e Humanas, Universidade Federal do ABC , 09210-580 
      Santo Andre, Brazil.
FAU - de Castro, Carlos E
AU  - de Castro CE
AD  - Centro de Ciencias Naturais e Humanas, Universidade Federal do ABC , 09210-580 
      Santo Andre, Brazil.
FAU - Riske, Karin A
AU  - Riske KA
AD  - Departamento de Biofisica, Universidade Federal de Sao Paulo , 04023-062 Sao 
      Paulo, Brazil.
FAU - da Silva, Maria C Carlan
AU  - da Silva MCC
AD  - Centro de Ciencias Naturais e Humanas, Universidade Federal do ABC , 09210-580 
      Santo Andre, Brazil.
FAU - Muraro, Paulo I R
AU  - Muraro PIR
AD  - Departamento de Quimica, Universidade Federal de Santa Maria , 97105-900 Santa 
      Maria, Brazil.
FAU - Schmidt, Vanessa
AU  - Schmidt V
AD  - Departamento de Quimica, Universidade Federal de Santa Maria , 97105-900 Santa 
      Maria, Brazil.
FAU - Giacomelli, Cristiano
AU  - Giacomelli C
AD  - Departamento de Quimica, Universidade Federal de Santa Maria , 97105-900 Santa 
      Maria, Brazil.
FAU - Giacomelli, Fernando C
AU  - Giacomelli FC
AUID- ORCID: 0000-0002-6872-9354
AD  - Centro de Ciencias Naturais e Humanas, Universidade Federal do ABC , 09210-580 
      Santo Andre, Brazil.
LA  - eng
PT  - Journal Article
DEP - 20170505
PL  - United States
TA  - Biomacromolecules
JT  - Biomacromolecules
JID - 100892849
RN  - 0 (Cations)
RN  - 0 (Methacrylates)
RN  - 0 (Polymethacrylic Acids)
RN  - 0 (four-arm poly(ethylene oxide)-b-poly(2-(diethylamino)ethyl methacrylate))
RN  - 0 (poly(2-(2-methoxyethoxy)ethyl methacrylate-co-oligo(ethylene glycol) 
      methacrylate))
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - 3WJQ0SDW1A (Polyethylene Glycols)
RN  - 9002-98-6 (Polyethyleneimine)
SB  - IM
MH  - Animals
MH  - Cations/chemistry
MH  - Cell Line, Transformed
MH  - Fibroblasts/cytology/metabolism
MH  - Gene Expression
MH  - *Gene Transfer Techniques
MH  - Genes, Reporter
MH  - Genetic Vectors/chemical synthesis/*metabolism
MH  - Green Fluorescent Proteins/genetics/metabolism
MH  - Macaca mulatta
MH  - Methacrylates/*chemistry
MH  - Nanoparticles/chemistry/*metabolism
MH  - Particle Size
MH  - Polyethylene Glycols/*chemistry
MH  - Polyethyleneimine/*chemistry
MH  - Polymethacrylic Acids/*chemistry
MH  - Static Electricity
EDAT- 2017/04/30 06:00
MHDA- 2018/03/16 06:00
CRDT- 2017/04/29 06:00
PHST- 2017/04/30 06:00 [pubmed]
PHST- 2018/03/16 06:00 [medline]
PHST- 2017/04/29 06:00 [entrez]
AID - 10.1021/acs.biomac.7b00344 [pii]
AID - 10.1021/acs.biomac.7b00344 [doi]
PST - ppublish
SO  - Biomacromolecules. 2017 Jun 12;18(6):1918-1927. doi: 10.1021/acs.biomac.7b00344. 
      Epub 2017 May 5.