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.

Papulo-Nodular Reactions in Black Tattoos as Markers of Sarcoidosis: Study of 92 Tattoo Reactions from a Hospital Material

“…However, carbon itself is inert and has seemingly never been reported to be an active allergen or epitope in the medical literature. Carbon black pigments have a negative or positive surface charge depending on the coating and surfactants and also chemisorbed oxygen complexes on their surface depending on manufacturing [17] . It is noteworthy that rush phenomenon also appeared in cases with granulomatous inflammation.…”

Surface chemistry of carbon nanoparticles functionally select their uptake in various stages of cancer cells

“…In this work, CNPs were prepared using two different strategies which included pre-and postpassivation. [23] In both of these techniques, the carbon core was synthesized from the agave nectar, a natural carbohydrate mainly containing glucose, fructose, and other carbohydrate sources. The surface of the carbon core was passivated with either linear (PEG's) or branched (PEI, etc.)…”

“…The choice of carbon as a nanoplatform was mainly chosen due to their ease of accessibility, low toxicity and facile surface chemistry. [23,24] We report here the systematic synthesis of sub 50 nm carbon nanoparticles (CNP) presenting neutral, anionic, and cationic surface functionalities. A subset of CNPs with 10, 20 and 40 nm hydrodynamic sizes are also synthesized with neutral surface headgroups.…”

“…8 1 H-NMR spectra of CNPs, comparing parent macromolecule PEG SO 3 H with surface passivated CNPs (CNP SO 3 H) showing the retention of peaks from PEG SO 3 H (marked with the black stars) while the purple stars indicate the features maintained from CNPs 23. 3.3 MECHANISMS OF CELLULAR ENTRY IN CELLS OF DIFFERENT CANCER STAGESCellular toxicity of CNPs in non-tumorigenic breast cells and tumorigenic breast cancer cells lines were evaluated by using MTT Assay(Figure 3.9).…”

In Situ Time‐Dependent and Progressive Oxidation of Reduced State Functionalities at the Nanoscale of Carbon Nanoparticles for Polarity‐Driven Multiscale Near‐Infrared Imaging

“…The UV–Vis absorption spectroscopic studies of BI passivated CNPs were carried out in the range of 230–800 nm (Figure S3, Supporting Information) to reveal an absorption band, similar in case of pristine/bare CNPs. The peak for CNP BIs was centered on 260 nm which can be attributed to the n–π* transition of the CO band and the π–π* transition of the conjugated CC band …”