Preparation of immunostimulatory single-walled carbon nanotube/CpG DNA complexes and evaluation of their potential in cancer immunotherapy

Abstract

Carbon nanotubes (CNTs) have many interesting properties. In particular, their photohyperthermic effect by near-infrared (NIR) irradiation could be used to kill cancer cells, and could thus be applied in photohyperthermic therapy. However, the solubility of CNTs must be improved before they can be used in biological applications. As DNA is reported to disperse the CNTs in aqueous solution with π-π interactions, we hypothesis that immunostimulatory CpG DNA may also disperse the CNTs in aqueous solution. In this study, we used CpG DNA to disperse single-walled CNTs (SWCNTs) in aqueous solution, in order to combine photohyperthermic effect and immunoactivation together to achieve a more effective cancer therapy. As expected, CpG DNA effectively dispersed the SWCNTs in aqueous solution via the formation of SWCNT/CpG DNA complexes. Moreover, the immunoreactivity of the SWCNT/CpG DNA complexes was investigated. The results showed that intratumoral administration of the SWCNT/CpG DNA complexes in mice enhanced the production level of inflammatory cytokines in tumor tissues. Finally, we evaluated the antitumor effects of the SWCNT/CpG DNA complexes in tumor-bearing mice. The result indicated that intratumoral administration of the SWCNT/CpG DNA complexes combined with NIR irradiation was a more effective approach to prevent the proliferation of tumor growth.

Phase Behavior of Ascorbyl Palmitate Coagels Loaded with Oligonucleotides as a New Carrier for Vaccine Adjuvants

“…In this context, the development of an efficient drug carrier system which could overcome these drawbacks and improve the adjuvant properties of CpG-ODN is mandatory. To this end, a great number of formulations have been explored, such as microspheres [22] liposomes [23] nanoparticles [24] and nanotubes [25] applying different material engineering and technological approaches. Although some of these formulations appeared promising, they also have had some problems mainly relating to manufacturing issues, such as scaling-up, toxicity associated with cationic materials, and the purity of the products [26,27].…”

Functional long circulating single walled carbon nanotubes for fluorescent/photoacoustic imaging-guided enhanced phototherapy

“…It is believed that SWCNT will be a promising cancer theranostic agent with appropriate surface modification to improve the biocompatibility and tumor targetability, because unmodified SWCNTs have highly hydrophobic surfaces and are not aqueous soluble. Modifying these hydrophilic surfaces can improve water solubility and improve SWCNTs performance via linking multiple active molecules such as peptides, genes, proteins, and drugs [26][27][28][29][30][31][32][33]. Evans blue (EB), a strong hydrophilic and non-toxic biological vessel stain, that can be used to coat SWCNTs via non-covalent adsorption and increased water solubility has been reported [34].…”

Photodynamic Action of Single-Walled Carbon Nanotubes

“…It was observed in another report that the photothermal action of SWNTs yielded heat shock protein 70 expression in tumor tissues. 60) The photogeneration of 1 O 2 by SWNTs was first reported in 2009 by Gandra et al 61) The 1 O 2 was detected by its emission signal at 1270 nm after excitation of SWNTs in aqueous solution at 532 nm via a two-photon absorption process. Importantly, the relative quantum yield of 1 O 2 generation (Φ Δ ) was inversely correlated with the intactness of the SWNTs; that is, the degree of defects of the graphene sheet.…”