Clinical translation of cell therapies requires strategies that can manufacture cells efficiently and economically. One promising way to reproducibly expand T cells for cancer therapy is by attaching the stimuli for T cells onto artificial substrates with high surface area. Here, we show that a carbon nanotube-polymer composite can act as an artificial antigen-presenting cell to efficiently expand the number of T cells isolated from mice. We attach antigens onto bundled carbon nanotubes and combined this complex with polymer nanoparticles containing magnetite and the T-cell growth factor interleukin-2 (IL-2). The number of T cells obtained was comparable to clinical standards using a thousand-fold less soluble IL-2. T cells obtained from this expansion were able to delay tumour growth in a murine model for melanoma. Our results show that this composite is a useful platform for generating large numbers of cytotoxic T cells for cancer immunotherapy.

No abstract

Efficient immunotherapy can be accomplished by expanding T cells outside the body using single walled carbon nanotube (SWNT) bundles presenting antibody stimuli. Owing to the large surface area of these bundles, which can reach 1560 m (2)/g, T cell stimulating antibodies such as anti-CD3, can be presented at high local concentrations inducing potent activation of T cells. We show that anti-CD3 adsorbed onto SWNT bundles stimulate cells more effectively than equivalent concentrations of soluble anti-CD3. Stimulation by antibody adsorbed onto SWNT is significantly higher than other high surface area materials (activated carbon, polystyrene, and C60 nanoparticles), suggesting unique properties of SWNT bundles for stimuli presentation. We demonstrate the surface area tunability of these bundles by chemical treatment and its effect on antibody adsorption and subsequent T cell activation. In addition, the T cell response varied with the concentration of SWNT in a concentration dependent manner. Antibody stimuli adsorbed onto SWNT bundles represent a novel paradigm for efficient activation of lymphocytes, useful for basic science applications and clinical immunotherapy.

High-quality single-walled carbon nanotubes (SWNT) with high yield were produced by using small-pore Co-MCM-41 catalyst, templated by a C10 surfactant and containing 3 wt % Co. A complete incorporation of Co ions in the silica matrix without formation of surface Co oxides and the contact time of the reaction, in the catalyst synthesis and the SWNT production, respectively, were the most critical factors to be considered. By controlling the reduction temperature and contact time in the reaction, the carbon yield could reach 34 wt % or higher with a selectivity of 96 wt % to SWNT. The metal content after purification of SWNT by base-acid treatments was 0.7 wt %, and the surface area was as high as 1800 m 2 /g. The metal surface occlusion effect by amorphous silica might play a key role in the stabilization of the completely reduced Co metallic clusters in the SWNT synthesis procedure, using small-pore C10 Co-MCM-41.

No abstract

Functionalized single-walled carbon nanotube bundles (f-bSWNT) adsorbed with T-cell-stimulating antibodies are shown to enhance both the kinetics and magnitude of T cell stimulation compared to the same concentration of free antibodies in solution. This enhancement is unique to f-bSWNT compared to other artificial substrates with high surface area and similar chemistry. We explored the origins of this enhanced activity with FRET microscopy and found the preferential formation of large antibody stimuli clusters (5 to 6 microm) on the surface of functionalized versus untreated nanotubes. This highlights the important aspect that antigen clusters can be formed on f-bSWNT, impacting the potency of the T cell stimulus. Clustering of T cell antigens on artificial substrates impacts the avidity of interaction with cells facilitating rapid stimulation dynamics and an overall greater magnitude of response. These findings support the use of chemically treated nanotube bundles as an efficient substrate for the presentation of antigens and point to their potential in clinical applications involving artificial antigen-presentation for ex vivo T cell expansion in adoptive immunotherapy.

Nanotechnology-enabled sensors (or nanosensors) will play an important role in enabling the progression toward ubiquitous information systems as the Internet of Things (IoT) emerges. Nanosensors offer new, miniaturized solutions in physiochemical and biological sensing that enable increased sensitivity, specificity, and multiplexing capability, all with the compelling economic drivers of low cost and high-energy efficiency. In the United States, Federal agencies participating in the National Nanotechnology Initiative (NNI) “Nanotechnology for Sensors and Sensors for Nanotechnology: Improving and Protecting Health, Safety, and the Environment” Nanotechnology Signature Initiative (the Sensors NSI), address both the opportunity of using nanotechnology to advance sensor development and the challenges of developing sensors to keep pace with the increasingly widespread use of engineered nanomaterials. This perspective article will introduce and provide background on the NNI signature initiative on sensors. Recent efforts by the Sensors NSI aimed at promoting the successful development and commercialization of nanosensors will be reviewed and examples of sensor nanotechnologies will be highlighted. Future directions and critical challenges for sensor development will also be discussed.

Antigen-specific activation of cytotoxic T cells can be enhanced up to three-fold more than soluble controls when using functionalized bundled carbon nanotube substrates ((b) CNTs). To overcome the denaturing effects of direct adsorption on (b) CNTs, a simple but robust method is demonstrated to stabilize the T cell stimulus on carbon nanotube substrates through non-covalent attachment of the linker neutravidin.