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Immunotherapies are now emerging as an efficient anticancer therapeutic strategy. Cancer immunotherapy utilizes the host's immune system to fight against cancer cells and has gained increasing interest due to its durable efficacy and low toxicity compared to traditional antitumor treatments, such as chemotherapy and radiotherapy (RT). Although the combination of RT and immunotherapy has drawn extensive attention in the clinical setting, the overall response rates are still low. Therefore, strategies for further improvement are urgently needed. Nanotechnology has been used in cancer immunotherapy and RT to target not only cancer cells but also the tumor microenvironment (TME), thereby helping to generate a long-term immune response. Nanomaterials can be an effective delivery system and a strong autophagy inducer, with the ability to elevate autophagy to very high levels. Interestingly, autophagy could play a critical role in optimal immune function, mediating cell-extrinsic homeostatic effects through the regulation of danger signaling in neoplastic cells under immunogenic chemotherapy and/or RT. In this review, we summarize the preclinical and clinical development of the combination of immunotherapy and RT in cancer therapy and highlight the latest progress in nanotechnology for augmenting the anticancer effects of immunotherapy and RT. The underlying mechanisms of nanomaterial-triggered autophagy in tumor cells and the TME are discussed in depth. Finally, we suggest the implications of these three strategies combined together to achieve the goal of maximizing the therapeutic advantages of cancer therapy and show recent advances in biomarkers for tumor response in the evaluation of those therapies.

Successful synthesis of glyconanoparticles has attracted much attention due to their various biointeractive capabilities, but it is still a challenge to understand different single-cell responses to exogenous particles among cell populations. Herein, we designed polyaniline-containing galactosylated gold nanoparticles (Au@PGlyco NPs) via in situ polymerization of ortho-nitrophenyl-β-galactoside assisted by Au nucleation. The nanogold-carrying polyaniline block produced electromagnetic enhancement in surface-enhanced Raman scattering (SERS). The underlying polymerization mechanism of ortho-nitrophenyl compounds via the formation of Au nanoparticles was investigated. Depending on how the galactoside moiety reacted with β-galactosidase derived from bacteria, the Au@PGlyco NPs-mediated SERS biosensor could detect low amounts of bacteria (∼1 × 102 CFU/mL). In addition, a high accumulation of Au@PGlyco NPs mediated the immune response of tumor-associated M2 macrophages to the immunogenic M1 macrophage transition, which was elicited by reactive oxygen levels biostimulation using single-cell SERS-combined fluorescence imaging. Our study suggested that Au@PGlyco NPs may serve as a biosensing platform with the labeling capacity on galactose-binding receptors expressed cell and immune regulation.

Simultaneous targeting of both the tumor microenvironment and cancer cells by a single nanomedicine has not been reported to date. Here, we report the dual properties of zero-valent-iron nanoparticle (ZVI-NP) to induce cancer-specific cytotoxicity and anti-cancer immunity. Methods: Cancer-specific cytotoxicity induced by ZVI-NP was determined by MTT assay. Mitochondria functional assay, immunofluorescence staining, Western blot, RT-qPCR, and ChIP-qPCR assays were used to dissect the mechanism underlying ZVI-NP-induced ferroptotic cancer cell death. The therapeutic potential of ZVI-NP was evaluated in immunocompetent mice and humanized mice. Immune cell profiles of allografts and ex vivo cultured immune cells were examined by flow cytometry analysis, RT-qPCR assay, and immunofluorescence. Results: ZVI-NP caused mitochondria dysfunction, intracellular oxidative stress, and lipid peroxidation, leading to ferroptotic death of lung cancer cells. Degradation of NRF2 by GSK3/β-TrCP through AMPK/mTOR activation was enhanced in such cancer-specific ferroptosis. In addition, ZVI-NP attenuated self-renewal ability of cancer and downregulated angiogenesis-related genes. Importantly, ZVI-NP augmented anti-tumor immunity by shifting pro-tumor M2 macrophages to anti-tumor M1, decreasing the population of regulatory T cells, downregulating PD-1 and CTLA4 in CD8+ T cells to potentiate their cytolytic activity against cancer cells, while attenuating PD-L1 expression in cancer cells in vitro and in tumor-bearing immunocompetent mice. In particular, ZVI-NPs preferentially accumulated in tumor and lung tissues, leading to prominent suppression of tumor growth and metastasis. Conclusions: This dual-functional nanomedicine established an effective strategy to synergistically induce ferroptotic cancer cell death and reprogram the immunosuppressive microenvironment, which highlights the potential of ZVI-NP as an advanced integrated anti-cancer strategy.

Lung cancer is considered among the deadliest cancers with a poor prognosis. Au@PG nanoparticles (NPs) are gold (Au)-based NPs featuring a polyaniline-based glyco structure (PG) generated from the polymerization of ortho-nitrophenyl-β-d-galactopyranoside (ONPG) with promising M1 macrophage polarization activity, resulting in tumor remodeling and from a cold to a hot microenvironment, which promotes the cytotoxic T cell response and tumor inhibition. The combination of Au@PG NPs and anti-programmed cell death protein 1 (PD-1) therapy improved tumor inhibition and immunosuppression, accompanied by the secretion of immunogenic cytokines. A one-pot synthetic method was developed to achieve glyco-condensation during the formation of Au@PG NPs, which induced macrophage polarization more efficiently than Au@glucose, Au@mannose, and Au@galactose NPs. The switch from M2 to M1 macrophages was dependent on NP size, with smaller Au@PG NPs performing better than larger ones, with effectiveness ranked as follows: 32.2 nm ≈ 29.8 nm26.4 nm18.3 nm. Cellular uptake by endocytosis induced size-dependent endoplasmic reticulum (ER) stress, which resulted in the activation of spleen tyrosine kinase (SYK), leading to immune modulations and macrophage polarization. Our results suggested the promising potential of Au@PG NPs in lung cancer immunotherapy.

In this study, we demonstrated that zero-valent iron (ZVI), which is widely used to remediate environmental contamination through the production of high-energy reactive oxygen species (ROS), exhibited differential cytotoxicity in cancerous cells and nonmalignant cells. Nanoparticles (NPs) with different shells exhibited distinct potencies against cancerous cells, which depended on their iron-to-oxygen ratios. Silver-coated ZVI NPs (ZVI@Ag) had the highest potency among synthesized ZVI NPs, and they simultaneously exhibited adequate biocompatibility with nonmalignant keratinocytes. The assessment of the intracellular dynamics of iron species revealed that the uptake of ZVI@Ag was similar between cancerous cells and nonmalignant cells during the first 2 h; however, only cancerous cells rapidly converted NPs into iron ions and generated large amounts of intracellular ROS, which was followed by apoptosis and autophagy induction. The aforementioned processes were prevented in the presence of iron ion chelators or by preoxidizing NPs before administration. Neutralization of lysosomal pH effectively reduced ZVI@Ag NP-induced programmed cell death. In the xenograft mouse model, cancer growth was significantly inhibited by a single dose of systematically administered NPs without significant weight loss in animals.

The development of optical organic nanoparticles (NPs) is desirable and widely studied. However, most organic chromophores are water-insoluble, and therefore, the derivatization and modification of these chromophores are difficult. Herein, we demonstrated a simple platform for the fabrication of organic nanoemitters by loading ten different organic dyes (molar masses of 479.1-1081.7 g/mol) into water-soluble polymer nanosponges composed of poly(styrene-alt-maleic acid) (PSMA). This nanolization strategy enables the incorporation of small commercial dyes (3.7–50% loading) and newly synthesized large photosensitive molecules (> 85% loading) into PSMA NPs and prevents the spontaneous aggregation of these hydrophobic chromophores in aqueous solutions. These low-cytotoxicity organic nanoparticles exhibited tunable red to near-infrared fluorescence emission for cellular imaging and biological tracking in vivo. Moreover, PSMA NPs loaded with designed NIR-photosensitive molecules were fabricated, and photodynamic therapy with these dye-loaded PSMA NPs for the photolysis of cancer cells was achieved when coupled with 808 nm laser excitation. Indeed, our work demonstrates a facile approach for increasing the biocompatibility and stability of organic dyes by loading them into water-soluble polymer-based carriers, providing a new perspective of organic optoelectronic materials in biomedical theranostic applications.

Nanotechnology has rapidly promoted the development of a new generation of industrial and commercial products; however, it has also raised some concerns about human health and safety. To evaluate the toxicity of the great diversity of nanomaterials (NMs) in the traditional manner, a tremendous number of safety assessments and a very large number of animals would be required. For this reason, it is necessary to consider the use of alternative testing strategies or methods that reduce, refine, or replace (3Rs) the use of animals for assessing the toxicity of NMs. Autophagy is considered an early indicator of NM interactions with cells and has been recently recognized as an important form of cell death in nanoparticle-induced toxicity. Impairment of autophagy is related to the accelerated pathogenesis of diseases. By using mechanism-based high-throughput screening in vitro, we can predict the NMs that may lead to the generation of disease outcomes in vivo. Thus, a tiered testing strategy is suggested that includes a set of standardized assays in relevant human cell lines followed by critical validation studies carried out in animals or whole organism models such as C. elegans (Caenorhabditis elegans), zebrafish (Danio rerio), and Drosophila (Drosophila melanogaster)for improved screening of NM safety. A thorough understanding of the mechanisms by which NMs perturb biological systems, including autophagy induction, is critical for a more comprehensive elucidation of nanotoxicity. A more profound understanding of toxicity mechanisms will also facilitate the development of prevention and intervention policies against adverse outcomes induced by NMs. The development of a tiered testing strategy for NM hazard assessment not only promotes a more widespread adoption of non-rodent or 3R principles but also makes nanotoxicology testing more ethical, relevant, and cost- and time-efficient.

An iron oxide (Fe3O4)-mediated photothermal treatment has been revealed as the next generation of noninvasive and nontoxic theranostic nanoagents compared with other inorganic nanoparticles. Nevertheless, iron oxide with NIR-mediated activity is limited by its inability to be mass produced and its long-lasting photon-to-thermal conversion. Herein, we develop using a green reagent, tannic acid (TNA), which assisted hydrothermal reaction to generate black Fe3O4 nanoparticles by using commercially available nanoptical γ-Fe2O3 NPs as a starting material. The phase transformation from γ-Fe2O3 to the reduced form of Fe3O4 is assisted by TNA in the solution phase. Based on the formation of the interfacial TNA-Fe chelation and the delicate phase transformation from γ-Fe2O3 to Fe3O4 structures, the colloidal black Fe3O4 nanoparticles exhibit broad absorption that covers the visible and NIR wavelengths. Specific interfacial ligand-to-metal charge transfers between the TNA and iron ions at the surface of iron oxide nanoparticles, improves the absorbance and leads to the highest photon-to-thermal conversion (η = 35.7%) at 808 nm compared with other iron oxide nanomaterials. After modifying d-mannose (MA) onto the surface of the Fe3O4@TNA nanoparticles, the local heat can efficiently transfer from the Fe3O4@TNA nanoparticles to the vicinity of the bacterial FimH adhesion molecule, causing extensive photothermal injury to O157:H7 and ESBL strain bacteria with over 99% cell death at 200 ppm[Fe] with 808 nm light at 2.25 mW/cm2. Based on its robust photostability, Fe3O4@TNA@MA shows photothermal bactericidal recyclability through magnetic collection, adhesion, and photothermal processes.

Infection patterns of parasites, including their prevalence, diversity and host specificity, can be impacted by many biological and environmental factors, but no study has focused on the circadian rhythms of vertebrate hosts, which may affect susceptibilities and encounter rates between hosts and vectors and further shape host-parasite associations. In this study, we focused on avian haemosporidians, a classical model in studies of host-parasite associations, and investigated the infection patterns in rescued raptors brought to the Beijing Raptor Rescue Center during 2007–2020. We first assessed the association between prevalence and host biotic traits, haemosporidian prevalence was higher in the nocturnal raptors than in the diurnal raptors, and the prevalence of Haemoproteus and Leucocytozoon in the nocturnal raptors was significantly higher than that in the diurnal raptors. Furthermore, we analysed the phylogenetic relationship and host-parasite network-level differences of haemosporidian parasites in diurnal and nocturnal raptors, and demonstrated that the lineages infecting the diurnal and nocturnal raptors were not clearly separated, but the nocturnal lifestyle led to a more specialized host-parasite network structure. These variations in host-parasite associations may be driven by different susceptibilities of the hosts and the diversity or abundance of vectors during the day and night. Our study provides new insight into host-parasite associations shaped by circadian rhythm and calls for more studies on the underlying mechanisms of parasite infection.

Although inorganic silver-based nanoparticles (NPs) have been used to replace antibiotics to treat environmental microorganisms, the silver ion diffusion mechanism takes at least hours to poison the bacteria and cannot destruct the bacteria immediately. In this paper, we developed a concise oxidation process of heterostructured Ag@AuAg hollow NPs in a H2O2/PBS solution to generate AgCl nanocrystals and high-oxidation-state (hos) metal species. The hos/AgCl-assembled NPs offered a strong redox reaction to kill bacteria at 1.25 ppm[Ag] which was lower minimal inhibition concentration value than the utility of Ag ions and Ag NPs. A rapid meet-dip-kill process to disintegrate the bacterial membrane was observed within 60 min. The continuous release of Ag ions from AgCl blocks served as a smart bactericide to sustainably inhibit bacterial growth up to 7 days. The hos/AgCl-based bactericide induced enhanced evolution of a distinctive subpopulation with rigid membrane structure against both Ag ions and Ag-based NPs. This Ag-resistant persister behaved the downregulation of energy consumption and the physical insulation for Ag ions by secreting bio-reductants to convert Ag ions to less toxic Ag NPs. Based on our findings, hos/AgCl-assembled NPs endowed multiple antibacterial effects with no prominent findings of toxicity in the liver and kidneys, which opens a new era to understand the antimicrobial mechanism and resistant risk of Ag-related NPs for future clinical and environmental application.

This thesis introduces some disadvantages of traditional Smart power-stealing prevention system and its transmission channel of wireless common grid at present, and proposes a new transmission technology. This new transmission technology is TD-LTE230M wireless power broadband private network technology, it is approved by National Radio Regulatory Commission in China and opened to electric power enterprises only. It has many advantages, for example, good anti-interference, reliability, security, so it is applied in Smart power-stealing prevention system. A new power-stealing prevention system is also proposed, and it is named TD-LTE230M smart power-stealing prevention system. This system is composed of load monitor, TD-LTE230M wireless data receiver, TD-LTE230M collection terminal, ammeter and host station. The thesis also introduces the TD-LTE230M wireless data receiver and its principle.

Clinical management of Clostridium difficile infection is still far from satisfactory as bacterial spores are resistant to many chemical agents and physical treatments. Certain types of nanoparticles have been demonstrated to exhibit anti-microbial efficacy even in multi-drug resistance bacteria. However, most of these studies failed to show biocompatibility to the mammalian host cells and no study has revealed in vivo efficacy in C. difficile infection animal models. The spores treated with 500 µg/mL Fe3-δO4 nanoparticles for 20 minutes, 64% of the spores were inhibited from transforming into vegetative cells, which was close to the results of the sodium hypochlorite-treated positive control. By cryo-electron micro-tomography, we demonstrated that Fe3-δO4 nanoparticles bind on spore surfaces and reduce the dipicolinic acid (DPA) released by the spores. In a C. difficile infection animal model, the inflammatory level triple decreased in mice with colonic C. difficile spores treated with Fe3-δO4 nanoparticles. Histopathological analysis showed a decreased intense neutrophil accumulation in the colon tissue of the Fe3-δO4 nanoparticle-treated mice. Fe3-δO4 nanoparticles, which had no influence on gut microbiota and apparent side effects in vivo, were efficacious inhibitors of C. difficile spore germination by attacking its surface and might become clinically feasible for prophylaxis and therapy.

How to improve the selectivity and efficacy of anticancer agents and to reduce side effects has always been a big challenge in clinical cancer therapy. Chemotherapeutic agents are usually toxic to both cancer and normal tissues, thus rendering compromised overall clinical outcome. Here we developed zero-valent iron nanoparticles (ZVI NPs) that exhibited selectivity toward higher toxicity to most cancerous cells thus opening a new era of anti-cancer therapy or adjuvant therapy through a novel molecular signaling pathway. We used head-and-neck cancer (HNC) cells and ovarian cancer (OVCA) cells to test the anti-cancer properties of ZVI NPs. The ZVI NPs served as a strong reactive oxygen species (ROS) inducer and caused irreversible mitochondria membrane potential lost in sensitive cancer cells that lead to cancer cell autophagy and growth suppression, while not significantly affect normal cell population. Further, the cytotoxicity of the ZVI NPs is highly depended on its redox state as oxidation of the NPs upon aging reduced their cytotoxic potency. In vivo study revealed a dose dependent tumor size reduction in tumor-bearing mice model without significant weight loss and pathological signs. These results suggest that ZVI NPs may serve as a new class of anticancer agent for a wide spectra of neoplastic diseases.

To evaluate the iron ion release profile of zero-valent iron (ZVI)-based nanoparticles (NPs) and their relationship with lysosomes in cancer cells, silica and mesoporous silica-coated ZVI NPs (denoted as ZVI@SiO2 and ZVI@mSiO2) were synthesized and characterized for the following study of cytotoxicity, intracellular iron ion release, and their underlying mechanisms. ZVI@mSiO2 NPs showed higher cytotoxicity than ZVI@SiO2 NPs in the OEC-M1 oral cancer cell line. In addition, internalized ZVI@mSiO2 NPs deformed into hollow and void structures within the cells after a 24-h treatment, but ZVI@SiO2 NPs remained intact after internalization. The intracellular iron ion release profile was also accordant with the structural deformation of ZVI@mSiO2 NPs. Burst iron ion release occurred in ZVI@mSiO2-treated cells within an hour with increased lysosome membrane permeability, which induced massive reactive oxygen species generation followed by necrotic and apoptotic cell death. Furthermore, inhibition of endosome&ndash, lysosome system acidification successfully compromised burst iron ion release, thereby reversing the cell fate. An in vivo test also showed a promising anticancer effect of ZVI@mSiO2 NPs without significant weight loss. In conclusion, we demonstrated the anticancer property of ZVI@mSiO2 NPs as well as the iron ion release profile in time course within cells, which is highly associated with the surface coating of ZVI NPs and lysosomal acidification.

Finding a cancer-selective drug that avoids damaging healthy cells and organs is a holy grail in medical research. In our previous studies, gold-coated iron (Fe@Au) nanoparticles showed cancer selective anti-cancer properties in vitro and in vivo but were found to gradually lose that activity with storage or “ageing„. To determine the reasons for this diminished anti-cancer activity, we examined Fe@Au nanoparticles at different preparation and storage stages by means of transmission electron microscopy combined with and energy-dispersive X-ray spectroscopy, along with X-ray diffraction analysis and cell viability tests. We found that dried and reconstituted Fe@Au nanoparticles, or Fe@Au nanoparticles within cells, decompose into irregular fragments of γ-F2O3 and agglomerated gold clumps. These changes cause the loss of the particles’ anti-cancer effects. However, we identified that the anti-cancer properties of Fe@Au nanoparticles can be well preserved under argon or, better still, liquid nitrogen storage for six months and at least one year, respectively.

Gold nanoparticles have been developed for the photoacoustic imaging, delivery of genes and laser induced photothermal therapy. In this study, we have developed oligonucleotide conjugated gold nanoparticles as the carrier for simultaneous DNA and anti-cancer nucleoside delivery. The polynucleotide-nanoparticle complex presented higher capacity in carrying 5-FU anti-cancer compounds than the original gold particles. The hydrodynamic size of the gold nanoparticles increased from 25 to 35 nm with an increase in the negative surface charge from -9.58 to 21.66 mV after polynucleotide conjugation and drug loading. A positive association between environmental pH and drug release was observed in PBS, which implied their potential use in the controlled localized drug release in the lower GI tract. The MTT assay revealed dose dependent cytotoxicity to colon cancer cell line than free compounds. These results suggest the potential use of this new polynucleotide-gold nanoparticles complex as the environmental controlled anti-cancer nanocapsule, especially suitable for per oral colon cancer chemotherapy.

Chemoresistance is a major challenge in cancer therapy. Cisplatin is commonly used for chemotherapy in patients with head-and-neck cancer (HNC), but it increases control of the disease by only 10-15%. Downregulation of proapoptotic pathways is a key determinant for chemoresistance in which gelsolin (GSN) is critically involved. We analyzed the association between GSN expression and cisplatin resistance in HNC cell lines, animals with HNC and cancer tissue samples from 58 cisplatin-treated patients with HNC. GSN expression levels were positively associated with chemoresistance in vitro and in vivo. Cisplatin-induced GSN downregulation was associated with the cleavage of GSN and the promotion of apoptosis. GSN silencing facilitated cisplatin-induced apoptosis in chemoresistant cells. In contrast, intact gelsolin was prosurvival in the presence of cisplatin by interacting with X-linked inhibitor of apoptosis protein (XIAP). In chemosensitive cells, cisplatin suppressed GSN-XIAP interaction, promoted translocation of XIAP from the perinuclear region to the nucleus and induced apoptosis. In chemoresistant cells, GSN was highly expressed, and cisplatin had no significant effect on GSN-XIAP interaction and apoptosis. We conclude that GSN is important for chemoresistance in HNC and may be an appropriate therapeutic target in chemoresistant cancers.

High temperature air combustion (HTAC) is an attractive technology of saving energy and controlling environment. The mathematical models of turbulent jet flame under the highly preheated air combustion condition are conducted in the paper. The mixture fraction/probability density function model is employed. The results show that the maximum flame temperature is decreased, the temperature in the HTAC furnace is more uniform than that in the conventional furnace, and the NOx emission is low. The numerical results are partially validated by some experimental measurements.

Purpose Altered gene expression is involved not only in the initiation of cancers, but also in tumor progression and treatment response. Cancer gene therapy is an emerging concept for advanced malignant disease management. However, most of current approaches in gene silencing act in the mRNA levels such as siRNA, ribozyme and anti-sense strategies. These approaches only gave partial and temporal gene expression suppression. Besides, delivery system of such approaches is also challenging. This study aimed to develop a Near-Infrared, Artificial, Targeted, Light-Activated Nanoscissor (NIR-ATLANS) to perform gene sequence specific double strand scission to permanently silence target cancer genes. Materials and methods The NIR-ATLANS comprised gold nanorod core with a monolayer of cypate-modified triplex-forming oligonucleotides (TFOs) that targets EGFP as a model system. The NIR-ATLANS activation specific wavelength is around 808 nm. After laser exposure at 808 nm peak wavelength, we used real-time polymerase chain reaction to check the gene cleavage efficiency. Results We discovered that the NIR-ATLANS could selectively target gene through electrophoretic mobility shift assay. When activated the nanoscissor by near-infrared laser, we observed decreased EGFP expression at both mRNA and protein level in the NIR-ATLANS combined lasing group, while not as significant in all other groups. Conclusions Our results showed a permanent gene silencing at the genomic level by combined ATLANS and laser activation. The gold nanorod could act as a quencher to prevent non-specific NIR-ATLANS cutting through free radical attack, thus protects non-target DNA from collateral damage. In our study, NIR-ATLANS successfully down regulate EGFP expression. Both reported gene and functional gene were able to be down regulated in cancer cell through our approach. We anticipate such technology hold a great potential in the future cancer gene therapy.

The aim of this paper is to present a discrete event model-based approach to simulate train movement with the considered energy-saving factor. We conduct extensive case studies to show the dynamic characteristics of the traffic flow and demonstrate the effectiveness of the proposed approach. The simulation results indicate that the proposed discrete event model-based simulation approach is suitable for characterizing the movements of a group of trains on a single railway line with less iterations and CPU time. Additionally, some other qualitative and quantitative characteristics are investigated. In particular, because of the cumulative influence from the previous trains, the following trains should be accelerated or braked frequently to control the headway distance, leading to more energy consumption.