title: Regulating Biocompatibility of Carbon Spheres via Defined Nanoscale Chemistry and a Careful Selection of Surface Functionalities.
abstract: A plethora of nanoarchitectures have been evaluated preclincially for applications in early detection and treatment of diseases at molecular and cellular levels resulted in limited success of their clinical translation. It is important to identify the factors that directly or indirectly affect their use in human. We bring a fundamental understanding of how to adjust the biocompatibility of carbon based spherical nanoparticles (CNPs) through defined chemistry and a vigilant choice of surface functionalities. CNPs of various size are designed by tweaking size (2-250 nm), surface chemistries (positive, or negatively charged), molecular chemistries (linear, dendritic, hyperbranched) and the molecular weight of the coating agents (MW 400-20 kDa). A combination of in vitro assays as tools were performed to determine the critical parameters that may trigger toxicity. Results indicated that hydrodynamic sizes are potentially not a risk factor for triggering cellular and systemic toxicity, whereas the presence of a highly positive surface charge and increasing molecular weight enhance the chance of inducing complement activation. Bare and carboxyl-terminated CNPs did present some toxicity at the cellular level which, however, is not comparable to those caused by positively charged CNPs. Similarly, negatively charged CNPs with hydroxyl and carboxylic functionalities did not cause any hemolysis.
authors.affiliation: Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Department of Bioengineering and Materials Science and Engineering, Urbana, 61801, USA.|Carle Foundation Hospital, Urbana, 61801, USA.
authors.forename: Santosh K
authors.initials: SK
authors.lastname: Misra
authors.affiliation: Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, 61801, USA.|Carle Foundation Hospital, Urbana, 61801, USA.
authors.forename: Huei-Huei
authors.initials: HH
authors.lastname: Chang
authors.affiliation: Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Department of Bioengineering and Materials Science and Engineering, Urbana, 61801, USA.
authors.forename: Prabuddha
authors.initials: P
authors.lastname: Mukherjee
authors.affiliation: Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Department of Bioengineering and Materials Science and Engineering, Urbana, 61801, USA.
authors.forename: Saumya
authors.initials: S
authors.lastname: Tiwari
authors.affiliation: Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Department of Bioengineering and Materials Science and Engineering, Urbana, 61801, USA.|Carle Foundation Hospital, Urbana, 61801, USA.
authors.forename: Ayako
authors.initials: A
authors.lastname: Ohoka
authors.affiliation: Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Department of Bioengineering and Materials Science and Engineering, Urbana, 61801, USA.|Carle Foundation Hospital, Urbana, 61801, USA.
authors.forename: Dipanjan
authors.initials: D
authors.lastname: Pan
mesh_terms: D001672:Biocompatible Materials / Q000138:chemical synthesis*; D002244:Carbon / Q000737:chemistry* / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D007928:Lethal Dose 50; D008970:Molecular Weight; D054118:Nanospheres / Q000737:chemistry* / Q000633:toxicity* / Q000648:ultrastructure; D010316:Particle Size; D013499:Surface Properties
chemical_list: D001672:Biocompatible Materials; D002244:Carbon