Magnetic resonance tracking of endothelial progenitor cells labeled with alkyl-polyethylenimine 2 kDa/superparamagnetic iron oxide in a mouse lung carcinoma xenograft model.

The potential of using endothelial progenitor cells (EPCs) in novel anticancer therapy and the repair of vascular injury has been increasingly recognized. In the present study, EPCs were labeled with N-alkyl-polyethylenimine 2 kDa (PEI2k)-stabilized superparamagnetic iron oxide (SPIO) to facilitate magnetic resonance imaging (MRI) of EPCs in a mouse lung carcinoma xenograft model. EPCs derived from human peripheral blood were labeled with alkyl-PEI2k/SPIO. The viability and activity of labeled cells were evaluated using proliferation, migration, and tubulogenesis assays. Alkyl-PEI2k/SPIO-labeled EPCs were injected intravenously (group 1) or mixed and injected together with A549 cells subcutaneously (group 2) into groups of six mice with severe combined immunodeficiency. The labeling efficiency with alkyl-PEI2k/SPIO at 7 µg Fe/mL concentration was approximately 100%. Quantitative analysis of cellular iron was 6.062 ± 0.050 pg/cell. No significant effects on EPC proliferation, migration, or tubulogenesis were seen after labeling. Seven-tesla micro-MRI showed the presence of schistic or linear hypointense regions at the tumor margins starting from days 7 to 8 after EPC administration. This gradually extended into the inner tumor layers in group 1. In group 2, tumor growth was accompanied by dispersion of low-signal intensity regions inside the tumor. Iron-positive cells identified by Prussian blue dye were seen at the sites identified using MRI. Human CD31-positive cells and mouse CD31-positive cells were present in both groups. Labeling EPCs with alkyl-PEI2k/SPIO allows noninvasive magnetic resonance investigation of EPC involvement in tumor neovasculature and is associated with excellent biocompatibility and MRI sensitivity.

Pressure-relief joints of initial support structural system used in tunnels with high-stress surrounding rock.

To address the problem of large deformations in weak surrounding rock tunnels under high ground stress, which cause damage to initial support structures, this study proposes a novel type of circumferential pressure-relief joint based on the concept of relieving deformation pressure of the surrounding rock. Key parameters of the pressure-relief joint, such as initial bearing capacity peak, constant bearing capacity, and allowable pressure-relief displacement, were obtained through numerical simulations and laboratory experiments. A comparison was made between the mechanical characteristics of rigid joints and the new type of pressure-relief joint. The applicability of the pressure-relief joint was verified through field tests, monitoring the surrounding rock pressure, internal forces in the steel frames, and the convergence displacement of the support structure. The results show that: (1) In the elastic stage, the stiffness of the new pressure-relief joint is similar to that of rigid joints. In the plastic stage, rigid joints fail directly, whereas the pressure-relief joint can control deformation and effectively release the deformation pressure of the surrounding rock while providing a constant bearing capacity. (2) The right arch foot in the experiment had poor rock quality, leading to high stress in the steel frame and significant horizontal displacement. After the deformation of the pressure-relief joint, the stress in the surrounding rock and steel frame significantly reduced, and the rate of horizontal deformation of the support structure slowed down. (3) The vertical and horizontal final displacements of the pressure-relief joint in the experiment were 61mm and 15mm, respectively, which did not exceed the allowable deformation values. The components of the support structure remained intact, ensuring safety. However, this study has limitations: the design of the new pressure-relief joint only allows for a vertical deformation of 150mm and a horizontal deformation of 50mm, limiting the range of pressure-relief deformation.

A cancer-specific activatable theranostic nanodrug for enhanced therapeutic efficacy via amplification of oxidative stress.

Rationale: Despite considerable advances, the reactive oxygen species (ROS)-mediated cancer treatment suffers from the problems of up-regulation of adaptive antioxidants in cancer cells as well as side effects to normal cells. Therefore, development of a new generation of cancer-specific nanomedicine capable of amplifying oxidative stress would be of great interest for accurate and effective cancer treatment. Methods: Herein, transferrin (Tf)-decorated, dihydroartemisinin (DHA), L-buthionine-sulfoximine (BSO), and CellROX-loaded liposomal nanoparticles (Tf-DBC NPs) were developed for precise cancer theranositcs. Tf-DBC NPs could specifically recognize cancer cells via Tf-Tf receptor binding and be uptaken into the lysosomes of cancer cells, where Tf-DBC NPs were activated to release Fe(II), DHA, and BSO. ROS was generated by DHA in the presence of Fe(II), and GSH was depleted by BSO to disrupt the redox balance in cancer cells. Furthermore, CellROX, as a fluorescent probe for imaging of intracellular oxidative stress, was used to monitor the therapeutic efficacy. Results: The integration of Tf, DHA, and BSO into the acidic pH-responsive liposomes selectively and effectively killed cancer cells and prevented the oxidative injury to normal cells. The high oxidative state was visualized at the tumor site and the amplification of oxidative stress enabled tumor eradication by Tf-DBC NPs, demonstrating the successful implementation of this novel strategy in vivo. Conclusion: Our study provides a new paradigm for the design of ROS-mediated therapeutics and offers a promising perspective for precise cancer treatment.