Dual stimulation of antigen presenting cells using carbon nanotube-based vaccine delivery system for cancer immunotherapy

Although anti−cancer immuno−based combinatorial therapeutic approaches have shown promising results, efficient tumour eradication demands further intensification of anti−tumour immune response. With the emerging field of nanovaccinology, multi−walled carbon nanotubes (MWNTs) have manifested prominent potentials as tumour antigen nanocarriers. Nevertheless, the utilization of MWNTs in co−delivering antigen along with different types of immunoadjuvants to antigen presenting cells (APCs) has not been investigated yet. We hypothesized that harnessing MWNT for concurrent delivery of cytosine−phosphate−guanine oligodeoxynucleotide (CpG) and anti-CD40 Ig (αCD40), as immunoadjuvants, along with the model antigen ovalbumin (OVA) could potentiate immune response induced against OVA−expressing tumour cells. We initially investigated the effective method to co−deliver OVA and CpG using MWNT to the APC. Covalent conjugation of OVA and CpG prior to loading onto MWNTs markedly augmented the CpG−mediated adjuvanticity, as demonstrated by the significantly increased OVA−specific T cell responses in vitro and in C57BL/6 mice. αCD40 was then included as a second immunoadjuvant to further intensify the immune response. Immune response elicited in vitro and in vivo by OVA, CpG and αCD40 was significantly potentiated by their co−incorporation onto the MWNTs. Furthermore, MWNT remarkably improved the ability of co−loaded OVA, CpG and αCD40 in inhibiting the growth of OVA−expressing B16F10 melanoma cells in subcutaneous or lung pseudo−metastatic tumour models. Therefore, this study suggests that the utilization of MWNTs for the co−delivery of tumour−derived antigen, CpG and αCD40 could be a competent approach for efficient tumours eradication.

Acute electronic cigarette use: nicotine delivery and subjective effects in regular users

Rationale Electronic cigarettes are becoming increasingly popular among smokers worldwide. Commonly reported reasons for use include the following: to quit smoking, to avoid relapse, to reduce urge to smoke, or as a perceived lower-risk alternative to smoking. Few studies, however, have explored whether electronic cigarettes (e-cigarettes) deliver measurable levels of nicotine to the blood. Objective This study aims to explore in experienced users the effect of using an 18-mg/ml nicotine first-generation e-cigarette on blood nicotine, tobacco withdrawal symptoms, and urge to smoke. Methods Fourteen regular e-cigarette users (three females), who are abstinent from smoking and e-cigarette use for 12 h, each completed a 2.5 h testing session. Blood was sampled, and questionnaires were completed (tobacco-related withdrawal symptoms, urge to smoke, positive and negative subjective effects) at four stages: baseline, 10 puffs, 60 min of ad lib use and a 60-min rest period. Results Complete sets of blood were obtained from seven participants. Plasma nicotine concentration rose significantly from a mean of 0.74 ng/ml at baseline to 6.77 ng/ml 10 min after 10 puffs, reaching a mean maximum of 13.91 ng/ml by the end of the ad lib puffing period. Tobacco-related withdrawal symptoms and urge to smoke were significantly reduced; direct positive effects were strongly endorsed, and there was very low reporting of adverse effects. Conclusions These findings demonstrate reliable blood nicotine delivery after the acute use of this brand/model of e-cigarette in a sample of regular users. Future studies might usefully quantify nicotine delivery in relation to inhalation technique and the relationship with successful smoking cessation/harm reduction.