PMID- 29894633
OWN - NLM
STAT- MEDLINE
DCOM- 20190514
LR  - 20190514
IS  - 1520-4812 (Electronic)
IS  - 1043-1802 (Linking)
VI  - 29
IP  - 7
DP  - 2018 Jul 18
TI  - Cross-Linked Enzyme Aggregates as Versatile Tool for Enzyme Delivery: Application 
      to Polymeric Nanoparticles.
PG  - 2225-2231
LID - 10.1021/acs.bioconjchem.8b00206 [doi]
AB  - Polymeric nanoparticles (NPs) represent one of the most promising tools in 
      nanomedicine and have been extensively studied for the delivery of 
      water-insoluble drugs. However, the efficient loading of therapeutic enzymes and 
      proteins in polymer-based nanostructures remains an open challenge. Here, we 
      report a synthesis method for a new enzyme delivery system based on cross-linked 
      enzyme aggregates (CLEAs) encapsulation into poly(lactide- co-glycolide) (PLGA) 
      NPs. We tested the encapsulation strategy on four enzymes currently investigated 
      for enzyme replacement therapy: palmitoyl protein thioesterase 1 (PPT1; defective 
      in NCL1 disease), galactosylceramidase (GALC; defective in globoid cell 
      leukodystrophy), alpha glucosidase (aGLU; defective in Pompe disease), and beta 
      glucosidase (bGLU; defective in Gaucher's disease). We demonstrated that our 
      system allows encapsulation of enzymes with excellent activity retention (usually 
      around 60%), thus leading to functional and targeted nanostructures suitable for 
      enzyme delivery. We then demonstrated that CLEA NPs efficiently deliver PPT1 in 
      cultured cells, with almost complete enzyme release occurring in 48 h. Finally, 
      we demonstrated that enzymatic activity is fully recovered in primary NCL1 
      fibroblasts upon treatment with PPT1 CLEA NPs.
FAU - Galliani, Marianna
AU  - Galliani M
AUID- ORCID: 0000-0003-4147-7457
AD  - Center of Nanotechnology Innovation@NEST , Istituto Italiano di Tecnologia , 
      56127 Pisa , Italy.
AD  - NEST , Scuola Normale Superiore and Istituto Nanoscienze-CNR , 56127 Pisa , 
      Italy.
FAU - Santi, Melissa
AU  - Santi M
AD  - Center of Nanotechnology Innovation@NEST , Istituto Italiano di Tecnologia , 
      56127 Pisa , Italy.
AD  - NEST , Scuola Normale Superiore and Istituto Nanoscienze-CNR , 56127 Pisa , 
      Italy.
FAU - Del Grosso, Ambra
AU  - Del Grosso A
AD  - NEST , Scuola Normale Superiore and Istituto Nanoscienze-CNR , 56127 Pisa , 
      Italy.
FAU - Cecchettini, Antonella
AU  - Cecchettini A
AD  - Institute of Clinical Physiology-CNR , 56127 Pisa , Italy.
AD  - Department of Experimental and Clinical Medicine , University of Pisa , 56127 
      Pisa , Italy.
FAU - Santorelli, Filippo Maria
AU  - Santorelli FM
AD  - Molecular Medicine , IRCCS Stella Maris , 56128 Pisa , Italy.
FAU - Hofmann, Sandra L
AU  - Hofmann SL
AD  - University of Texas Southwestern Medical Center , Dallas , Texas 75390 , United 
      States.
FAU - Lu, Jui-Yun
AU  - Lu JY
AD  - University of Texas Southwestern Medical Center , Dallas , Texas 75390 , United 
      States.
FAU - Angella, Lucia
AU  - Angella L
AD  - NEST , Scuola Normale Superiore and Istituto Nanoscienze-CNR , 56127 Pisa , 
      Italy.
FAU - Cecchini, Marco
AU  - Cecchini M
AUID- ORCID: 0000-0002-9688-2356
AD  - NEST , Scuola Normale Superiore and Istituto Nanoscienze-CNR , 56127 Pisa , 
      Italy.
FAU - Signore, Giovanni
AU  - Signore G
AUID- ORCID: 0000-0002-0067-2240
AD  - Center of Nanotechnology Innovation@NEST , Istituto Italiano di Tecnologia , 
      56127 Pisa , Italy.
AD  - NEST , Scuola Normale Superiore and Istituto Nanoscienze-CNR , 56127 Pisa , 
      Italy.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180702
PL  - United States
TA  - Bioconjug Chem
JT  - Bioconjugate chemistry
JID - 9010319
RN  - 0 (Drug Carriers)
RN  - 0 (Enzymes)
RN  - 0 (Polymers)
RN  - 1SIA8062RS (Polylactic Acid-Polyglycolic Acid Copolymer)
RN  - EC 3.1.2.- (Thiolester Hydrolases)
RN  - EC 3.1.2.22 (palmitoyl-protein thioesterase)
RN  - EC 3.2.1.20 (alpha-Glucosidases)
RN  - EC 3.2.1.21 (beta-Glucosidase)
RN  - EC 3.2.1.46 (Galactosylceramidase)
SB  - IM
MH  - Cells, Cultured
MH  - Drug Carriers/*chemistry
MH  - Enzymes/*administration & dosage
MH  - Fibroblasts/metabolism
MH  - Galactosylceramidase/administration & dosage
MH  - Humans
MH  - Methods
MH  - Nanoparticles/*chemistry
MH  - Polylactic Acid-Polyglycolic Acid Copolymer/therapeutic use
MH  - Polymers/*therapeutic use
MH  - Solubility
MH  - Thiolester Hydrolases/administration & dosage
MH  - alpha-Glucosidases/administration & dosage
MH  - beta-Glucosidase/administration & dosage
EDAT- 2018/06/13 06:00
MHDA- 2019/05/15 06:00
CRDT- 2018/06/13 06:00
PHST- 2018/06/13 06:00 [pubmed]
PHST- 2019/05/15 06:00 [medline]
PHST- 2018/06/13 06:00 [entrez]
AID - 10.1021/acs.bioconjchem.8b00206 [doi]
PST - ppublish
SO  - Bioconjug Chem. 2018 Jul 18;29(7):2225-2231. doi: 
      10.1021/acs.bioconjchem.8b00206. Epub 2018 Jul 2.