In situ assembled titanium carbide-based heterojunctions for the synergistic enhancement of NIR-II photothermal/photodynamic therapy against breast cancer.

The combined use of photothermal therapy (PTT) and photodynamic therapy (PDT) could circumvent the drawbacks of each individual therapeutic strategy, resulting in an enhanced antitumor effect. However, the lack of highly effective photo-agents that are irradiation-safe in the biologically transparent window hinder the advancement of phototherapy clinically. Hence, in this study, a charge separation engineering strategy was adopted to fabricate a nanoplatform with heterojunctions, namely, in situ TiO2-loaded MXene (Ti3C2/TiO2 heterojunctions). This nanoplatform exhibited reduced bandgap (1.68 eV), enhanced NIR-II photothermal conversion efficiency (44.98%), and extended absorption edge compared to pristine TiO2 for enhanced photodynamic effect. More importantly, the proliferation of tumor cells could be efficiently inhibited at a 5 mm chicken breast depth after 1064 nm laser irradiation, and the intracellular ROS production significantly increased under 660 nm or even 1064 nm laser irradiation with heterojunctions (HJs) compared with that of TiO2. Moreover, the in vivo data further confirmed that the as-prepared heterojunctions could efficiently eradicate tumors efficiently via improved photothermal effect with NIR-II laser irradiation and upregulated ROS production. Collectively, the reported HJs strategy provides an opportunity for the success of combinational PTT and PDT therapy in tumor treatment.

A reactive oxygen species-replenishing coordination polymer nanomedicine disrupts redox homeostasis and induces concurrent apoptosis-ferroptosis for combinational cancer therapy.

Reactive oxygen species (ROS) are important signal molecules and imbalanced ROS level could lead to cell death. Elevated ROS levels in tumor tissues offer an opportunity to design ROS-responsive drug delivery systems (DDSs) or ROS-based cancer therapies such as chemodynamic therapy. However, their anticancer efficacies are hampered by the ROS-consuming nature of these DDSs as well as the high concentration of reductive agents like glutathione (GSH). Here we developed a doxorubicin (DOX)-incorporated iron coordination polymer nanoparticle (PCFD) for efficient chemo-chemodynamic cancer therapy by using a cinnamaldehyde (CA)-based ROS-replenishing organic ligand (TCA). TCA can ROS-responsively release CA to supplement intracellular ROS and deplete GSH by a thiol-Michael addition reaction, which together with DOX-triggered ROS upregulation and Fe3+-enabled GSH depletion facilitated efficient DOX release and enhanced Fenton reaction, thereby inducing redox dyshomeostasis and cancer cell death in a concurrent apoptosis-ferroptosis way. Both in vitro and in vivo studies revealed that ROS-replenishing PCFD exhibited much better anticancer effect than ROS-consuming control nanoparticle PAFD. The ingenious ROS-replenishing strategy could be expanded to construct versatile ROS-responsive DDSs and ROS-based nanomedicines with potentiated anticancer activity. STATEMENT OF SIGNIFICANCE: We develop a doxorubicin (DOX)-incorporated iron coordination polymer nanoparticle (PCFD) for efficient chemo-chemodynamic cancer therapy by using a cinnamaldehyde-based reactive oxygen species (ROS)-replenishing organic ligand. This functional ligand can ROS-responsively release cinnamaldehyde to supplement intracellular H2O2 and deplete glutathione (GSH) by a thiol-Michael addition reaction, which together with DOX-triggered ROS upregulation and Fe3+-enabled GSH depletion facilitates efficient DOX release and enhanced Fenton reaction, thereby inducing redox dyshomeostasis and cancer cell death in a concurrent apoptosis-ferroptosis way. Both in vitro and in vivo studies reveal that ROS-replenishing PCFD exhibit much better anticancer effect than ROS consuming counterpart. This study provides a facile and straightforward strategy to design ROS amplifying nanoplatforms for cancer treatment.

Spatiotemporal variability of phytoplankton functional groups in a shallow eutrophic lake from cold, arid regions.

In the shallow eutrophic lakes in cold, arid regions, the phytoplankton functional groups and the factors that drive their spatiotemporal variabilities remain unclear. Samples were collected from Lake Ulansuhai in April, August, and October 2017 (wet season) and January 2018 (dry season). Based on the functional group classification method, 23 phytoplankton functional groups with 5 major ones were identified. During the wet season, high amounts of nutrients, elevated temperatures, and heavy rainfall produced spatiotemporal variabilities in phytoplankton communities, whereas during the dry season, the frozen period was the critical factor that determined the spatiotemporal variabilities in the phytoplankton communities. Through redundancy analyses, total nitrogen and total phosphorus concentrations were observed to directly affect the phytoplankton growth; algal growth affected the chemical oxygen demand, and pH and environmental factors interacted with the phytoplankton growth. These results highlight the complex feedbacks of shallow eutrophic lake ecosystems in arid regions. Group TC (represented by Lyngbya) was correlated with Huangtai algae. In August, a Huangtai algal bloom resulted in a relatively stable water column, which was conducive to group TC growth. Therefore, the presence of certain phytoplankton functional groups can indicate the current lake conditions by identifying the coverage of Huangtai algae, which provides a scientific basis for an early warning of a potential algal bloom.

Bioinspired Artificial Tobacco Mosaic Virus with Combined Oncolytic Properties to Completely Destroy Multidrug-Resistant Cancer.

Although biomimetic virus-like strategies have been widely used in antitumor applications, construction of uniquely shaped virus-like agents and optimization of their specific morphological features to achieve diverse antitumor functions are worthwhile pursuits. Here, a novel strategy to construct an artificial tobacco mosaic virus (ATMV) that closely mimics the structure of the rod-like tobacco mosaic virus (TMV) is developed. The supramolecular array is self-assembled from small, repeated subunits of tailor-made capsid-mimicking dendrons onto RGD-modified single-walled carbon nanotube to construct the ATMVs with high structural stability. The ATMVs are tactfully designed with shielding, targeting, and arming approaches, including shielding the viruses against premature elimination, selectively targeting tumor tissue, and arming the viruses with oncolytic abilities. The elongated particles are concealed in blood until they arrived at a tumor site, then they induce robust composite oncolytic processes including cytomembrane penetration, endoplasmic reticulum disruption to cause Ca2+ release, chemotherapeutic delivery, and photothermal therapy. Excitingly, the ATMVs not only lyse primary infected cells, but permeate adjacent cells for secondary infection, spreading cell-to-cell and continuing to induce lysis even deep in solid tumors. This work inspires a uniquely shaped virus-like agent with tactically optimized oncolytic functions that completely defeated large drug-resistant colon tumor (LoVo/Adr, ≈500 mm3 ).

The change of the state of cell membrane can enhance the synthesis of menaquinone in Escherichia coli.

Menaquinone (MK) was an attractive membrane-bound intracellular chemical. To enhance its production, we tried to find the relationship between its synthesis and the state of cell membrane in producing strain. Due to non-ionic surfactant-polyoxyethylene oleyl ether (POE) and plant oil-cedar wood oil (CWO) can typically increase extracellular secretion and intracellular synthesis of MK respectively, the effect of these two substances on cell morphology, physical properties of cell membrane was investigated. Finally, two engineering strains were constructed to verify whether the state of cell membrane can enhance MK synthesis. The result showed that the edge of cells was broken when POE added in the medium. Other physical properties such as total fatty acid content decreased by 40.7% and the ratio of saturated fatty acids to unsaturated fatty acids decreased from 1.58 ± 0.05 to 1.31 ± 0.04. Meanwhile, cell membrane leakage was enhanced from 7.14 to 64.31%. Different from POE group, cell membrane was intact in CWO group. Moreover, the ratio of saturated fatty acids to unsaturated fatty acids increased from 1.58 ± 0.05 to 1.78 ± 0.04 and the average lipid length decreased from 16.05 ± 0.08 to 15.99 ± 0.10. Two constructed strains, especially Escherichia coli DH5α FatB, exhibited strong MK secretion ability and the extracellular MK reached 10.71 ± 0.19 mg/L. An understanding of these functionary mechanisms could not only provide a new idea for the synthesis of MK, but also provide a reference to increase the yield of intracellular membrane-bound metabolites.