Intrinsic targeting of inflammatory cells in the brain by polyamidoamine dendrimers upon subarachnoid administration.
OBJECTIVE
Understanding the interactions between nanomaterials and disease processes is crucial for designing effective therapeutic approaches. This article explores the unusual neuroinflammation targeting of dendrimers (with no targeting ligands) in the brain, with significant consequences for nanoscale materials in medicine.


METHODS
The in vivo biodistribution of fluorescent-labeled neutral generation-4- polyamidoamine dendrimers (∼4 nm) in a rabbit model of cerebral palsy was explored following subarachnoid administration.


RESULTS
These dendrimers, with no targeting ligands, were localizing in activated microglia and astrocytes (cells responsible for neuroinflammation), even in regions far moved from the site of injection, in newborn rabbits with maternal inflammation-induced cerebral palsy.


CONCLUSIONS
This intrinsic ability of dendrimers to localize inactivated microglia and astrocytes can enable targeted delivery of therapeutics in disorders such as cerebral palsy, Alzheimer's and multiple sclerosis.
Department of Pediatrics (Critical Care Medicine), Children's Hospital of Michigan, Wayne State University, Detroit, MI 48201, USA.
Hui
H
Dai
Raghavendra S
RS
Navath
Bindu
B
Balakrishnan
Bharath Raja
BR
Guru
Manoj K
MK
Mishra
Roberto
R
Romero
Rangaramanujam M
RM
Kannan
Sujatha
S
Kannan
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D002547:Cerebral Palsy / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D050091:Dendrimers / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D016650:Fluorescein-5-isothiocyanate / Q000737:chemistry; D008297:Male; D017628:Microglia / Q000378:metabolism*; D011817:Rabbits; D013346:Subarachnoid Space / Q000378:metabolism*
D050091:Dendrimers; C104700:PAMAM Starburst; D016650:Fluorescein-5-isothiocyanate