RESUMO
The launched hepatitis B vaccine could induce powerful antibodies, whereas it failed to improve potent cellular immune responses due to that the Th2-type response-induced aluminum adjuvant was adopted. Here, to target antigen-presenting cells under the epidermis and induce potent cellular and humoral immune responses, mannose-modified poly D,L-lactide-co-glycolic acid (PLGA) was synthesized and nanoparticle (MNP)-loaded hepatitis B surface antigen (HBsAg) protein was prepared. HBsAg could be slowly released and highly presented to lymphocytes which facilitated to produce long-lasting immunity based on characters of PLGA. In vitro uptake test results showed that MNPs could enhance internalization in bone marrow-derived dendritic cells (BMDCs) and RAW 264.7 cells. Subcutaneous delivery of MNPs into mice kept humoral immune and strengthened cellular immune responses. Experimental results indicated that MNPs showed significantly modified properties compared with parental PLGA nanoparticles. Thus, the obtained MNPs could be a promising vehicle for hepatitis B vaccine delivery.
Assuntos
Vacinas contra Hepatite B/administração & dosagem , Vírus da Hepatite B/efeitos dos fármacos , Imunização/métodos , Manose/administração & dosagem , Nanopartículas/administração & dosagem , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/administração & dosagem , Animais , Sistemas de Liberação de Medicamentos/métodos , Excipientes/administração & dosagem , Excipientes/química , Feminino , Antígenos de Superfície da Hepatite B/administração & dosagem , Vacinas contra Hepatite B/química , Vírus da Hepatite B/imunologia , Manose/química , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Células RAW 264.7RESUMO
In mechanical anomaly detection, algorithms with higher accuracy, such as those based on artificial neural networks, are frequently constructed as black boxes, resulting in opaque interpretability in architecture and low credibility in results. This article proposes an adversarial algorithm unrolling network (AAU-Net) for interpretable mechanical anomaly detection. AAU-Net is a generative adversarial network (GAN). Its generator, composed of an encoder and a decoder, is mainly produced by algorithm unrolling of a sparse coding model, which is specially designed for feature encoding and decoding of vibration signals. Thus, AAU-Net has a mechanism-driven and interpretable network architecture. In other words, it is ad hoc interpretable. Moreover, a multiscale feature visualization approach for AAU-Net is introduced to verify that meaningful features are encoded by AAU-Net, helping users to trust the detection results. The feature visualization approach enables the results of AAU-Net to be interpretable, i.e., post hoc interpretable. To verify AAU-Net's capability of feature encoding and anomaly detection, we designed and performed simulations and experiments. The results show that AAU-Net can learn signal features that match the dynamic mechanism of the mechanical system. Considering the excellent feature learning ability, unsurprisingly, AAU-Net achieves the best overall anomaly detection performance compared with other algorithms.
RESUMO
To improve the water solubility and tumor targeting ability of docetaxel (DTX), and thus enhance the drug's antitumor efficacy and safety, a novel folate receptor (FR)-targeted cyclodextrin drug delivery vehicle (FA-CD) was successfully synthesized. The synthesis of the designed cyclodextrin was confirmed by Fourier transform infrared spectroscopy (FTIR), proton nuclear magnetic resonance (1H NMR), and differential scanning calorimetry (DSC). The in vitro cytotoxicity was investigated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the results showed that no significant differences (p>0.05) appeared in cytotoxicity between the different cyclodextrins in the different cell lines. Besides, the DTX/FA-CD inclusion complex was prepared. The cellular uptake and competition assays were examined using the HepG2, HeLa, and KB cell lines, which have different levels of folate receptor expression. Interestingly, the Cy5.5/FA-CD complex had higher uptake in the HepG2, HeLa, and KB cells, compared with non-targeted Cy5.5/CD complex (p<0.001). The time-dependent drug uptake into KB cells observed by LSCM confirmed the drug delivery via endocytic routes. Data from the competition assays, especially in KB cells, showed that a significant inhibitory effect (p<0.001) was obtained when the concentration of FA was increased, and suggested that the Cy5.5/FA-CD was internalized through a FR-mediated mechanism. Moreover, the in vitro bioactivity assay also demonstrated efficient antitumor activity, and the order of the cell viabilities (% of control) was OB>HepG2>HeLa>KB for DTX/FA-CD (p<0.001). For DTX/CD, however, it displayed minimum antitumor behavior in all cell types. An apoptosis study by FCM and LSCM also revealed that the FA-modified complexes were more effective in inducing apoptosis in FR-expressing cells. Finally, an in vivo biodistribution study in KB-bearing healthy mice revealed that the DTX/FA-CD complex has enhanced tumor-targeting efficacy and diminished systemic side effects. These results suggest that the novel FR-targeted cyclodextrin complex is a promising alternative as an anticancer drug delivery system.