Carbon nanomaterials have received recent attention as biomolecular carriers, [1][2][3][4][5] capable of transporting covalently bonded drugs or molecular probes across cell membranes.The poor cellular penetration of many small molecules and proteins can be overcome by conjugation to a nanomaterial carrier, whose size, shape, and surface chemistry can be engineered for optimal cellular uptake. The seminal work cited above [1,2] focused on carbon nanotubes but we believe that spherical carbon nanoparticles may be a superior platform. Their simple geometry and freedom from entanglement ensures a consistent effective size for cell uptake and a uniform surface chemistry. Indeed, particle size and shape are key variables determining the rates and mechanisms of cellular uptake. Endocytotic uptake has recently been proposed to occur at an optimum diameter of about 50 nm with significantly lower rates for both larger and smaller particles.[6] Larger particles are typically taken up by phagocytosis, a separate cellular mechanism driven by the actin myosin cortex in professional phagocytic cells such as macrophages and amoeba. [6] In targeted therapies, uptake by the mononuclear phagocyte system can be minimized by using hydrophilic nanoparticles smaller than 100 nm, [7,8] allowing the carriers to reach the target tissue. We see great potential to develop carbon-based biomolecular carrier platforms in which nanoparticle size and surface chemistry are tuned to i) preferentially target nonphagocytic cells, and ii) control biodistribution and cellular uptake to localize nanoparticle conjugates at diseased sites.[8]Carbon nanoparticles are potentially biocompatible, nonimmunogenic [9] and offer a range of options for carrying active agents, which include surface adsorption or deposition, pore filling, incorporation in the carbon matrix, and surface covalent coupling. A variety of carbon nanoparticles have been synthesized, [10][11][12][13][14][15] motivated almost entirely by non-biological applications. An exception is Rudge et al., [16] who developed iron-carbon composite microparticles (0.5-5 lm) for targeted chemotherapy delivered through intra-arterial injection. Carbon nanoparticles are readily available in the form of carbon blacks, commodity materials with primary particle sizes ranging from 12 to 100 nm. The primary nanoparticles in carbon blacks are linked into fused fractal aggregates, however, which exhibit much larger and uncontrolled effective particle sizes. In addition, carbon-black particles have concentric (onionlike) graphene layer symmetry, and, in common with most other high-temperature nanocarbon forms, have hydrophobic, low-polarity, low-reactivity surfaces that present challenges for dispersion and functionalization.We are specifically interested in developing carbon nanoparticles as platforms for delivery to mesothelial cells. For this application the materials development should focus on the following goals: i) explicit control of particle composition and size across the endocytic/phagocytic size rang...
