Polymeric nanoparticle system to target activated microglia/macrophages in spinal cord injury.
The possibility to control the fate of the cells responsible for secondary mechanisms following spinal cord injury (SCI) is one of the most relevant challenges to reduce the post traumatic degeneration of the spinal cord. In particular, microglia/macrophages associated inflammation appears to be a self-propelling mechanism which leads to progressive neurodegeneration and development of persisting pain state. In this study we analyzed the interactions between poly(methyl methacrylate) nanoparticles (PMMA-NPs) and microglia/macrophages in vitro and in vivo, characterizing the features that influence their internalization and ability to deliver drugs. The uptake mechanisms of PMMA-NPs were in-depth investigated, together with their possible toxic effects on microglia/macrophages. In addition, the possibility to deliver a mimetic drug within microglia/macrophages was characterized in vitro and in vivo. Drug-loaded polymeric NPs resulted to be a promising tool for the selective administration of pharmacological compounds in activated microglia/macrophages and thus potentially able to counteract relevant secondary inflammatory events in SCI.
IRCCS Istituto di Ricerche Farmacologiche "Mario Negri", Dipartimento di Neuroscienze, via La Masa 19, 20156 Milan, Italy.
Simonetta
S
Papa
Politecnico di Milano, Dipartimento di Chimica, Materiali e Ingegneria Chimica "Giulio Natta", via Mancinelli 7, 20131 Milan, Italy.
Raffaele
R
Ferrari
IRCCS Istituto di Ricerche Farmacologiche "Mario Negri", Dipartimento di Ambiente e Salute, via La Masa 19, 20156 Milan, Italy.
Massimiliano
M
De Paola
Politecnico di Milano, Dipartimento di Chimica, Materiali e Ingegneria Chimica "Giulio Natta", via Mancinelli 7, 20131 Milan, Italy.
Filippo
F
Rossi
IRCCS Istituto di Ricerche Farmacologiche "Mario Negri", Dipartimento di Ambiente e Salute, via La Masa 19, 20156 Milan, Italy.
Alessandro
A
Mariani
IRCCS Istituto di Ricerche Farmacologiche "Mario Negri", Dipartimento di Neuroscienze, via La Masa 19, 20156 Milan, Italy.
Ilaria
I
Caron
IRCCS Istituto di Ricerche Farmacologiche "Mario Negri", Dipartimento di Neuroscienze, via La Masa 19, 20156 Milan, Italy.
Eliana
E
Sammali
Università di Pavia, Dipartimento di Biologia e Biotecnologie "L. Spallanzani", via Ferrata, 9, 27100 Pavia, Italy.
Marco
M
Peviani
IRCCS Istituto di Ricerche Farmacologiche "Mario Negri", Dipartimento di Neuroscienze, via La Masa 19, 20156 Milan, Italy.
Valentina
V
Dell'Oro
Politecnico di Milano, Dipartimento di Chimica, Materiali e Ingegneria Chimica "Giulio Natta", via Mancinelli 7, 20131 Milan, Italy.
Claudio
C
Colombo
Institute for Chemical and Bioengineering, ETH Zurich, Campus Hoenggerberg, HCI F125, Wolfgang Pauli Str. 10, 8093 Zurich, Switzerland.
Massimo
M
Morbidelli
IRCCS Istituto di Ricerche Farmacologiche "Mario Negri", Dipartimento di Neuroscienze, via La Masa 19, 20156 Milan, Italy.
Gianluigi
G
Forloni
Politecnico di Milano, Dipartimento di Chimica, Materiali e Ingegneria Chimica "Giulio Natta", via Mancinelli 7, 20131 Milan, Italy; Department of Innovative Technologies, University of Applied Sciences and Arts of Southern Switzerland, SUPSI, via Cantonale, CH-6928 Manno, Switzerland; Swiss Institute for Regenerative Medicine, CH-6807 Taverne, Switzerland.
Giuseppe
G
Perale
Politecnico di Milano, Dipartimento di Chimica, Materiali e Ingegneria Chimica "Giulio Natta", via Mancinelli 7, 20131 Milan, Italy.
Davide
D
Moscatelli
IRCCS Istituto di Ricerche Farmacologiche "Mario Negri", Dipartimento di Neuroscienze, via La Masa 19, 20156 Milan, Italy. Electronic address: pietro.veglianese@marionegri.it.
Pietro
P
Veglianese
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002232:Carbocyanines / Q000008:administration & dosage / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004396:Coloring Agents / Q000008:administration & dosage / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D005260:Female; D020100:Hydrogels; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D019904:Polymethyl Methacrylate / Q000008:administration & dosage* / Q000737:chemistry; D013116:Spinal Cord / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000378:metabolism*
D002232:Carbocyanines; D004396:Coloring Agents; D004337:Drug Carriers; D020100:Hydrogels; D008070:Lipopolysaccharides; C098830:TO-PRO-3; D019904:Polymethyl Methacrylate
Drug delivery; Macrophage; Microglia; Nanoparticle; Spinal cord injury