A cancer cell membrane coated, doxorubicin and microRNA co-encapsulated nanoplatform for colorectal cancer theranostics.

Endogenous microRNAs (miRNA) in tumors are currently under exhaustive investigation as potential therapeutic agents for cancer treatment. Nevertheless, RNase degradation, inefficient and untargeted delivery, limited biological effect, and currently unclear side effects remain unsettled issues that frustrate clinical application. To address this, a versatile targeted delivery system for multiple therapeutic and diagnostic agents should be adapted for miRNA. In this study, we developed membrane-coated PLGA-b-PEG DC-chol nanoparticles (m-PPDCNPs) co-encapsulating doxorubicin (Dox) and miRNA-190-Cy7. Such a system showed low biotoxicity, high loading efficiency, and superior targeting ability. Systematic delivery of m-PPDCNPs in mouse models showed exceptionally specific tumor accumulation. Sustained release of miR-190 inhibited tumor angiogenesis, tumor growth, and migration by regulating a large group of angiogenic effectors. Moreover, m-PPDCNPs also enhanced the sensitivity of Dox by suppressing TGF-ß signal in colorectal cancer cell lines and mouse models. Together, our results demonstrate a stimulating and promising m-PPDCNPs nanoplatform for colorectal cancer theranostics.

Changes in root chemical diversity along an elevation gradient of Changbai Mountain, China.

Root chemical traits play a critical role in plant resource use strategies and ecosystem nutrient cycling; however, the chemical diversity of multiple elements of fine root and community chemical assembly belowground are poorly understood. Here, we measured 13 elements (C, N, K, Ca, Mg, S, P, Al, Fe, Na, Mn, Zn, and Cu) in the fine roots of 204 plant species along elevational transect from 540 to 2357 m of Changbai Mountain, China to explore the variation, diversity, and community assembly of root chemical traits. At the species level, the concentrations of macronutrients (N, K, Ca, Mg, S, and P) decreased, whereas the trace metals (Fe, Mn, and Zn) increased with elevation. Root chemical traits at the community level systematically shifted along elevational gradients showing a pattern similar to that at the species level, which were mainly influenced by climate and soil rather than species diversity. In general, the interactions of climate and soil were the main drivers of root chemical assembly for woody layers, whereas soil factors played significant role for root chemical assembly for herb layer. The chemical assembly of rock-derived element P was mainly driven by soil factors. Meanwhile, root chemical diversities were mainly regulated by species diversity, the interactions of climate and soil, and soil factors in the tree, shrub, and herb layers, respectively. A better understanding of plant root chemical diversity and community chemical assembly will help to reveal the role of chemical traits in ecosystem functioning.

Network-based protein-protein interaction prediction method maps perturbations of cancer interactome.

The perturbations of protein-protein interactions (PPIs) were found to be the main cause of cancer. Previous PPI prediction methods which were trained with non-disease general PPI data were not compatible to map the PPI network in cancer. Therefore, we established a novel cancer specific PPI prediction method dubbed NECARE, which was based on relational graph convolutional network (R-GCN) with knowledge-based features. It achieved the best performance with a Matthews correlation coefficient (MCC) = 0.84±0.03 and an F1 = 91±2% compared with other methods. With NECARE, we mapped the cancer interactome atlas and revealed that the perturbations of PPIs were enriched on 1362 genes, which were named cancer hub genes. Those genes were found to over-represent with mutations occurring at protein-macromolecules binding interfaces. Furthermore, over 56% of cancer treatment-related genes belonged to hub genes and they were significantly related to the prognosis of 32 types of cancers. Finally, by coimmunoprecipitation, we confirmed that the NECARE prediction method was highly reliable with a 90% accuracy. Overall, we provided the novel network-based cancer protein-protein interaction prediction method and mapped the perturbation of cancer interactome. NECARE is available at: https://github.com/JiajunQiu/NECARE.

Visualization nanozyme based on tumor microenvironment "unlocking" for intensive combination therapy of breast cancer.

Nanozymes as artificial enzymes that mimicked natural enzyme-like activities have received great attention in cancer therapy. However, it remains a great challenge to design nanozymes that precisely exert its activity in tumor without producing off-target toxicity to surrounding normal tissues. Here, we report a synergetic enhancement strategy through the combination between nanozyme and tumor vascular normalization to destruct tumors, which was based on tumor microenvironment (TME) "unlocking." This nanozyme that we developed not only has photothermal properties but also can produce reactive oxygen species efficiently under the stimulation of TME. Moreover, this nanozyme also showed remarkable imaging performance in fluorescence imaging in the second near-infrared region and magnetic resonance imaging for visualization tracing in vivo. The process of combination therapy showed remarkable therapeutic effect for breast cancer. This study provides a therapeutic strategy by the cooperation between multifunctional nanozyme and tumor vascular normalization for intensive combination therapy of breast cancer.

Ultrasensitive and simultaneous determination of RNA modified nucleotides by sheathless interfaced capillary electrophoresis-tandem mass spectrometry.

A label-free ultrasensitive determination of eight RNA modified nucleotides simultaneously was first established based on a sheathless capillary electrophoresis-tandem mass spectrometry system. This system performed well using only 500 pg-5 ng practical RNA samples, and a downward trend of most target nucleotides in HCT 116 cells was observed with the increase of nickel concentration.

Atomic-Thick PtNi Nanowires Assembled on Graphene for High-Sensitivity Extracellular Hydrogen Peroxide Sensors.

H2O2 sensors with high sensitivity and selectivity are essential for monitoring the normal activities of cells. Inorganic catalytic nanomaterials show the obvious advantage in boosting the sensitivity of H2O2 sensors; however, the H2O2 detection limit of reported inorganic catalysts is still limited, which is not suitable for high-sensitivity detection of H2O2 in real cells. Herein, novel atomic-thick PtNi nanowires (NWs) were synthesized and assembled on reduced graphene oxide (rGO) via an ultrasonic self-assembly method to attain PtNi NWs/rGO composite for boosting the electroanalysis of H2O2. In 0.05 M phosphate-buffered saline (pH 7.4) solution, the as-prepared PtNi NWs/rGO shows an extraordinary performance in quantifying H2O2 in a wide range of concentrations from 1 nM to 5.3 mM. Significantly, the detection limit of PtNi NWs/rGO reaches unprecedented 0.3 nM at an applied potential of -0.6 V (vs Ag/AgCl), which enables the detection of traced amounts of H2O2 released from Raw 264.7 cells. The excellent performance of H2O2 detection on PtNi NWs/rGO is ascribed to the high-density active sites of atomic-thick PtNi NWs.

Validation of Bevacizumab Therapy Effect on Colon Cancer Subtypes by Using Whole Body Imaging in Mice.

PURPOSE: Preclinical imaging offers a useful tool for monitoring cancer biological behavior and therapy in vivo without the necessity of animal surgery. The following paper describes our examination of tumor progress and anti-angiogenic therapy with Bevacizumab on colon cancer subtypes (SW480 and SW620) by using different non-invasive real-time in vivo imaging techniques. PROCEDURES: Color Doppler ultrasound imaging (CDUI) was used to observe the formation of new blood vessels; a homemade fluorescence reflectance imaging (FRI) apparatus was mainly used to test the difference in VEGFR2 expression between the tumor subtypes. Briefly, 15 Balb/c nude mice bearing subcutaneous SW480 and SW620 xenografts were randomly divided into Control and Drug groups. Bevacizumab treatment lasted for 3 weeks. All images were captured pre- and post-treatment. At the end of experiment, all mice were euthanized, and tumor tissue was collected and analyzed by immunohistochemical staining. RESULTS: Expression of VEGFR2 was found to be slightly (10 %) but significantly higher for the SW620 cells than for SW480 cells. In addition, SW620 has shown to be more vascularized than SW480 subtype. After 3-week Bevacizumab therapy, no blood vessels were found within 83 % of SW620, while it was 67 % in SW480; the increase of SW620 tumor volume post-treatment was only 3.17-fold compared with the tumor volume pre-treatment, and 4.51-fold higher in SW480. CONCLUSION: Our data suggest that SW480 and SW620 cell lines respond differently to Bevacizumab therapy in vivo. Because of higher vascularization, and subsequently higher reduction by drug of new blood vessels and tumor growth rate, xenografts derived from the metastatic SW620 cell line have a better chance of being successfully treated with Bevacizumab compared with those derived from the primary tumor SW480 cell line.