Chemoimmunotherapy combines chemotherapy based on anticancer drugs with immunotherapy based on immune activators to eliminate or inhibit the growth of cancer cells. In this study, water-insoluble paclitaxel (PTX) was dispersed in water using hyaluronic acid (HA) to generate a tumor-associated antigen in the tumor microenvironment. Cytosine–phosphate–guanosine oligodeoxynucleotides (CpG ODNs) were used to enhance the T helper (Th) 1 immune response. However, CpG ODNs also induced the secretion of interleukin-10 (IL-10) that reduces the Th1 response and enhances the T helper 2 (Th2) response. Therefore, RNA interference was used to downregulate IL-10 secretion from bone marrow-derived dendritic cells (BMDCs). For the combined immunomodulation of BMDCs, we fabricated two types of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) containing CpG ODNs to activate BMDCs via Toll-like receptor 9 (CpG ODN-encapsulated PLGA NPs, PCNs) or a small interfering RNA to silence IL-10 (IL-10 small interfering RNA-encapsulated PLGA NPs, PINs). Treatment of BMDCs with both types of PLGA NPs increased the Th1/Th2 cytokine (IL-12/IL-10) expression ratio, which is important for the effective induction of an antitumor immune response. After primary injection with the HA/PTX complex, the tumor-associated antigen was generated and taken up by tumor-recruited BMDCs. After a secondary injection with immunomodulating PCNs and PINs, the BMDCs became activated and migrated to the tumor-draining lymph nodes. As a result, the combination of chemotherapy using the HA/PTX complex and immunotherapy using PCNs and PINs not only efficiently inhibited tumor growth but also increased the animal survival rate. Taken together, our results suggest that the sequential treatment of cancer cells with a chemotherapeutic agent and immunomodulatory nanomaterials represents a promising strategy for efficient cancer therapy.
Foot-and-mouth disease virus (FMDV) is a highly contagious disease that affects cloven-hoofed animals. The traditional diagnostic methods for FMDV have several drawbacks such as cross-reactivity, low sensitivity, and low selectivity. To overcome these drawbacks, we present an optical and electrochemical dual-modal approach for the specific detection of FMDV serotypes O and A by utilizing a magnetic nanoparticle labeling technique with resorufin β-d-glucopyranoside (res-β-glc) and β-glucosidase (β-glc), without the use of typical lateral flow assay or polymerase chain reaction. FMDV serotypes O and A were reacted with pan-FMDV antibodies that recognize all seven FMDV serotypes (O, A, C, Asia 1, SAT 1, SAT 2, and SAT 3). The antigen–antibody complex was then immobilized on magnetic nanoparticles and reacted with β-glc-conjugated FMDV type O or type A antibodies. Subsequently, the addition of res-β-glc resulted in the release of fluorescent resorufin and glucose owing to catalytic hydrolysis by β-glc. The detection limit of fluorescent signals using a fluorescence spectrophotometer was estimated to be log(6.7) and log(5.9) copies/mL for FMDV type O and A, respectively, while that of electrochemical signals using a glucometer was estimated to be log(6.9) and log(6.1) copies/mL for FMDV type O and A, respectively. Compared with a commercially available lateral flow assay diagnostic kit for immunochromatographic detection of FMDV type O and A, this dual-modal detection platform offers approximately four-fold greater sensitivity. This highly sensitive and accurate dual-modal detection method can be used for effective disease diagnosis and treatment, and will find application in the early-stage diagnosis of viral diseases and next-generation diagnostic platforms.
Multi-walled carbon nanotubes (MWCNTs) have variable metal impurities, but little is known about the impact of soluble metal impurities on the toxicity of MWCNTs. Here, we evaluated the role of soluble metal impurities to the acute inflammogenic potential of MWCNTs, using five types of high purity MWCNTs (>95%). MWCNTs and their soluble fractions collected at 24 h after incubation in phosphate-buffered saline showed diverse metal impurities with variable concentrations. The fiber-free soluble fractions produced variable levels of reactive oxygen species (ROS), and the iron level was the key determinant for ROS production. The acute inflammation at 24 h after intratracheal instillation of MWCNTs to rats at 0.19, 0.63, and 1.91 mg MWCNT/kg body weight (bw) or fiber-free supernatants from MWCNT suspensions at 1.91 and 7.64 mg MWCNT/kg bw showed that the number of granulocytes, a marker for acute inflammation, was significantly increased with a good dose-dependency. The correlation study showed that neither the levels of iron nor the ROS generation potential of the soluble fractions showed any correlations with the inflammogenic potential. However, the total concentration of transition metals in the soluble fractions showed a good correlation with the acute lung inflammogenic potential. These results implied that metal impurities, especially transitional metals, can contribute to the acute inflammogenic potential of MWCNTs, although the major parameter for the toxicity of MWCNTs is size and shape.