title: Multifunctionalized CMCht/PAMAM dendrimer nanoparticles modulate the cellular uptake by astrocytes and oligodendrocytes in primary cultures of glial cells.
abstract: The efficiency of the treatments involving CNS disorders is commonly diminished by the toxicity, reduced stability and lack of targeting of the administered neuroactive compounds. In this study, we have successfully multifunctionalized CMCht/PAMAM dendrimer nanoparticles by coupling the CD11b antibody and loading MP into the nanoparticles. The modification of the new antibody-conjugated nanoparticles was confirmed by S-TEM observation and (1) H NMR and FTIR spectroscopy. Cytotoxicity assays revealed that the conjugates did not affect the viability of both primary cultures of glial and microglial cells. Trace analyses of FITC-labelled nanoparticles revealed that the uptake of antibody-conjugated nanoparticles was conserved in microglial cells but significantly decreased in astrocytes and oligodendrocytes. Thus, this study demonstrates that antibody conjugation contributes to a modulation of the internalization of these nanocarriers by different cell types, which might be of relevance for specific targeting of CNS cell populations.
authors.affiliation: ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: Susana R
authors.initials: SR
authors.lastname: Cerqueira
authors.forename: Bárbara L
authors.initials: BL
authors.lastname: Silva
authors.forename: Joaquim M
authors.initials: JM
authors.lastname: Oliveira
authors.forename: João F
authors.initials: JF
authors.lastname: Mano
authors.forename: Nuno
authors.initials: N
authors.lastname: Sousa
authors.forename: António J
authors.initials: AJ
authors.lastname: Salgado
authors.forename: Rui L
authors.initials: RL
authors.lastname: Reis
mesh_terms: D000818:Animals; D000906:Antibodies / Q000737:chemistry / Q000276:immunology; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D039481:CD11b Antigen / Q000737:chemistry / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000031:analogs & derivatives* / Q000737:chemistry; D050091:Dendrimers / Q000737:chemistry*; D004337:Drug Carriers / Q000138:chemical synthesis / Q000494:pharmacology*; D004339:Drug Compounding; D004705:Endocytosis / Q000187:drug effects; D016650:Fluorescein-5-isothiocyanate; D009682:Magnetic Resonance Spectroscopy; D008775:Methylprednisolone / Q000737:chemistry / Q000494:pharmacology; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry* / Q000627:therapeutic use / Q000648:ultrastructure; D009836:Oligodendroglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009928:Organ Specificity; D061251:Primary Cell Culture; D051381:Rats; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D000906:Antibodies; D039481:CD11b Antigen; D050091:Dendrimers; D004337:Drug Carriers; C509295:ITGAM protein, human; C104700:PAMAM Starburst; C514968:carboxymethyl-chitosan; D048271:Chitosan; D016650:Fluorescein-5-isothiocyanate; D008775:Methylprednisolone