Mahmoud Elsabahy1, Sandani Samarajeewa, Jeffery E Raymond, Corrie Clark, Karen L Wooley. 1. Department of Chemistry, Department of Chemical Engineering, Laboratory for Synthetic-Biologic Interactions, Texas A&M University, P.O. Box 30012, 3255 TAMU, College Station, Texas 77842-3012, United States ; Department of Pharmaceutics, Faculty of Pharmacy, Assiut Clinical Center of Nanomedicine, Al-Rajhy Liver Hospital, Assiut University, Assiut, Egypt.
Abstract
The development of stable nanoparticles that can withstand the changing conditions experienced in a biological setting and also be of low toxicity and immunogenicity is of particular importance to address the problems associated with currently utilized nanotechnology-based therapeutics and diagnostics. The use of crosslinked nanoparticles continues to receive special impetus, due to their robust structure and high kinetic stability, and they have recently been shown to induce lower cytotoxicity than their non-crosslinked micellar counterparts. In the current study, poly(acrylamidoethylamine)-block-poly(DL-lactide) (PAEA90-b-PDLLA40) copolymers were synthesized, self-assembled in water to yield nanoscopic polymeric micelles, and the effects of decorating the micellar surface with poly(ethylene glycol) (i.e. PEGylation) and crosslinking the PAEA layer to varying extents on the physicochemical characteristics, cytotoxicity and immunotoxicity of the nanoparticles were studied. Herein, we report for the first time that crosslinking can efficiently reduce the immunotoxicity of polymeric nanomaterials. In addition, increasing the degree of crosslinking further reduced the accessibility of biomolecules to the core of the nanoparticles and decreased their cytotoxicity and immunotoxicity. It is also highlighted that crosslinking can be more efficient than PEGylation in reducing the immunotoxicity of nanomaterials. Shell-crosslinking of block copolymer micelles, therefore, is expected to advance their clinical development beyond the earlier known effects, and to broaden the implications in the field of nanomedicine.
The development of stable nanoparticles that can withstand the changing conditions experienced in a biological setting and also be of low n class="Disease">toxicity anpan>d immunpan>ogenicity is of particular impan> class="Gene">portance to address the problems associated with currently utilized nanotechnology-based therapeutics and diagnostics. The use of crosslinked nanoparticles continues to receive special impetus, due to their robust structure and high kinetic stability, and they have recently been shown to induce lower cytotoxicity than their non-crosslinked micellar counterparts. In the current study, poly(acrylamidoethylamine)-block-poly(DL-lactide) (PAEA90-b-PDLLA40) copolymers were synthesized, self-assembled in water to yield nanoscopic polymeric micelles, and the effects of decorating the micellar surface with poly(ethylene glycol) (i.e. PEGylation) and crosslinking the PAEA layer to varying extents on the physicochemical characteristics, cytotoxicity and immunotoxicity of the nanoparticles were studied. Herein, we report for the first time that crosslinking can efficiently reduce the immunotoxicity of polymeric nanomaterials. In addition, increasing the degree of crosslinking further reduced the accessibility of biomolecules to the core of the nanoparticles and decreased their cytotoxicity and immunotoxicity. It is also highlighted that crosslinking can be more efficient than PEGylation in reducing the immunotoxicity of nanomaterials. Shell-crosslinking of block copolymer micelles, therefore, is expected to advance their clinical development beyond the earlier known effects, and to broaden the implications in the field of nanomedicine.
Authors: Sandani Samarajeewa; Aida Ibricevic; Sean P Gunsten; Ritu Shrestha; Mahmoud Elsabahy; Steven L Brody; Karen L Wooley Journal: Biomacromolecules Date: 2013-03-19 Impact factor: 6.988
Authors: R Plummer; R H Wilson; H Calvert; A V Boddy; M Griffin; J Sludden; M J Tilby; M Eatock; D G Pearson; C J Ottley; Y Matsumura; K Kataoka; T Nishiya Journal: Br J Cancer Date: 2011-02-01 Impact factor: 7.640
Authors: Yannick P Borguet; Sarosh Khan; Amandine Noel; Sean P Gunsten; Steven L Brody; Mahmoud Elsabahy; Karen L Wooley Journal: Biomacromolecules Date: 2018-03-11 Impact factor: 6.988