Dual-driven nanomotors enable tumor penetration and hypoxia alleviation for calcium overload-photo-immunotherapy against colorectal cancer.

The treatment efficacies of conventional medications against colorectal cancer (CRC) are restricted by a low penetrative, hypoxic, and immunosuppressive tumor microenvironment. To address these restrictions, we developed an innovative antitumor platform that employs calcium overload-phototherapy using mitochondrial N770-conjugated mesoporous silica nanoparticles loaded with CaO2 (CaO2-N770@MSNs). A loading level of 14.0 wt% for CaO2-N770@MSNs was measured, constituting an adequate therapeutic dosage. With the combination of oxygen generated from CaO2 and hyperthermia under near-infrared irradiation, CaO2-N770@MSNs penetrated through the dense mucus, accumulated in the colorectal tumor tissues, and inhibited tumor cell growth through endoplasmic reticulum stress and mitochondrial damage. The combination of calcium overload and phototherapy revealed high therapeutic efficacy against orthotopic colorectal tumors, alleviated the immunosuppressive microenvironment, elevated the abundance of beneficial microorganisms (e.g., Lactobacillaceae and Lachnospiraceae), and decreased harmful microorganisms (e.g., Bacteroidaceae and Muribaculaceae). Moreover, together with immune checkpoint blocker (αPD-L1), these nanoparticles showed an ability to eradicate both orthotopic and distant tumors, while potentiating systemic antitumor immunity. This treatment platform (CaO2-N770@MSNs plus αPD-L1) open a new horizon of synergistic treatment against hypoxic CRC with high killing power and safety.

Near-Infrared-Enpowered Nanomotor-Mediated Targeted Chemotherapy and Mitochondrial Phototherapy to Boost Systematic Antitumor Immunity.

Phototherapy is an important strategy to inhibit tumor growth and activate antitumor immunity. However, the effect of photothermal/photodynamic therapy (PTT/PDT) is restricted by limited tumor penetration depth and unsatisfactory potentiation of antitumor immunity. Here, a near-infrared (NIR)-driven nanomotor is constructed with a mesoporous silicon nanoparticle (MSN) as the core, end-capped with Antheraea pernyi silk fibroin (ApSF) comprising arginine-glycine-aspartate (RGD) tripeptides. Upon NIR irradiation, the resulting ApSF-coated MSNs (DIMs) loading with photosensitizers (ICG derivatives, IDs) and chemotherapeutic drugs (doxorubicin, Dox) can efficiently penetrate into the internal tumor tissues and achieve effective phototherapy. Combined with chemotherapy, a triple-modal treatment (PTT, PDT, and chemotherapy) approach is developed to induce the immunogenic cell death of tumor cells and to accelerate the release of damage-associated molecular patterns. In vivo results suggest that DIMs can promote the maturation of dendritic cells and surge the number of infiltrated immune cells. Meanwhile, DIMs can polarize macrophages from M2 to M1 phenotypes and reduce the percentages of immunosuppressive Tregs, which reverse the immunosuppressive tumor microenvironment and activate systemic antitumor immunity. By achieving synergistic effects on the tumor inhibition and the antitumor immunity activation, DIMs show great promise as new nanoplatforms to treat metastatic breast cancer.

The Influence of Soil Erodibility and Saturated Hydraulic Conductivity on Soil Nutrients in the Pingshuo Opencast Coalmine, China.

Soil erodibility (K factor) and saturated hydraulic conductivity (Ks) are essential indicators for the estimation of erosion intensity and can potentially influence soil nutrient losses, making them essential parameters for the evaluation of land reclamation quality. In this study, 132 soil samples from 22 soil profiles were collected to measure soil physicochemical properties (e.g., particle size distribution, bulk density and soil nutrient content) and calculate the K factor and Ks of reclaimed soils across the South Dump of the Pingshuo opencast coalmine in the Loess Plateau, China. Geostatistical analysis and the kriging interpolation were employed to quantify the spatial variations in the K factor and Ks in different layers. The results show that the K factor at 0−10 cm is obviously lower than that of other soil layers due to the external input of organic matter, while the Ks tends to decrease along with soil depth. Horizontally, the K factor at 0−10 cm and 50−60 cm shows a decreasing tendency from west to east, while that of other soil layers seems not to show any spatial distribution pattern along latitude or longitude. Meanwhile, the Ks at 0−10 cm presents a striped distribution pattern, while that of other soil layers shows a patchy pattern. On the other hand, the independent-sample t-test and Spearman's correlation analysis were carried out to determine the effects of soil erodibility on total nitrogen (TN), soil organic matter (SOM), available phosphorus (AP) and potassium (AK). Overall, the K factor is negatively correlated with TN (r = −0.362, p < 0.01) and SOM contents (r = −0.380, p < 0.01), while AP and AK contents are mainly controlled by Ks. This study provides insight on the optimization of reclamation measures and the conservation of soil nutrients in reclaimed land of similar ecosystems.