PDGFRß-Antagonistic Affibody-Mediated Tumor-Targeted Tumor Necrosis Factor-Alpha for Enhanced Radiotherapy in Lung Cancer.

The morbidity and mortality of lung cancer are still the highest among all malignant tumors. Radiotherapy plays an important role in clinical treatment of lung cancer. However, the effect of radiotherapy is not ideal due to the radiation resistance of tumor tissues. Abnormalities in tumor vascular structure and function affect blood perfusion, and oxygen transport is impeded, making tumor microenvironment hypoxic. Tumor hypoxia is the major cause of radiotherapy resistance. By promoting tumor vessel normalization and enhancing vascular transport function, tumor hypoxia can be relieved to reduce radiotherapy resistance and increase tumor radiotherapy sensitivity. In our previous study, a pericytes-targeted tumor necrosis factor alpha (named Z-TNFα) was first constructed and produced by genetically fusing the platelet-derived growth factor receptor ß (PDGFRß)-antagonistic affibody (ZPDGFRß) to the TNFα, and the Z-TNFα induced normalization of tumor vessels and improved the delivery of doxorubicin, enhancing tumor chemotherapy. In this study, the tumor vessel normalization effect of Z-TNFα in lung cancer was further clarified. Moreover, the tumor hypoxia improvement and radiosensitizing effect of Z-TNFα were emphatically explored in vivo. Inspiringly, Z-TNFα specifically accumulated in Lewis lung carcinoma (LLC) tumor graft and relieved tumor hypoxia as well as inhibited HIF-1α expression. As expected, Z-TNFα significantly increased the effect of radiotherapy in mice bearing LLC tumor graft. In conclusion, these results demonstrated that Z-TNFα is also a promising radiosensitizer for lung cancer radiotherapy.

Polydopamine Nanostructure-Enhanced Water Interaction with pH-Responsive Manganese Sulfide Nanoclusters for Tumor Magnetic Resonance Contrast Enhancement and Synergistic Ferroptosis-Photothermal Therapy.

Rational structure design benefits the development of efficient nanoplatforms for tumor theranostic application. In this work, a multifunctional polydopamine (PDA)-coated manganese sulfide (MnS) nanocluster was prepared. The polyhydroxy structure of PDA enhanced the water interaction with pH-responsive MnS nanoclusters via hydrogen bonds. At pH 5.5 conditions, the spin-lattice relaxation rate of MnS nanoclusters dramatically increased from 5.76 to 19.33 mM-1·s-1 after the PDA coating, which can be beneficial for efficient tumor magnetic resonance imaging. In addition, PDA endowed MnS nanoclusters with excellent biocompatibility and good photothermal conversion efficiency, which can be used for efficient tumor photothermal therapy (PTT). Furthermore, MnS nanoclusters possess the ability to release H2S in the acidic tumor microenvironment, effectively inhibiting mitochondrial respiration and adenosine triphosphate production. As a result, the expression of heat shock protein was obviously reduced, which can reduce the resistance of tumor cells to photothermal stimulation and enhance the efficacy of PTT. The released Mn2+ also displayed efficient peroxidase and glutathione oxidase-like activity, effectively inducing tumor cell ferroptosis and apoptosis at the same time. Therefore, this nanoplatform could be a potential nanotheranostic for magnetic resonance contrast enhancement and synergistic ferroptosis-PTT of tumors.

Fabrication of High Thermal Conductivity Nanodiamond/Aramid Nanofiber Composite Films with Superior Multifunctional Properties.

Polymer-based thermally conductive materials are preferred for heat dissipation owing to their low density, flexibility, low cost, and easy processing. Researchers have been trying to develop a polymer-based composite film with excellent thermal conductivity (TC), mechanical strength, thermal stability, and electrical properties. However, synergistically achieving these properties in a single material is still a challenge. To address the above requirements, we prepared poly(diallyldimethylammonium chloride)-functionalized nanodiamond (ND@PDDA)/aramid nanofiber (ANF) composite films using a self-assembly strategy. Owing to a strong interfacial interaction arising from electrostatic attraction, ND particles attract strongly along the ANF axis to form ANF/ND "core-sheath" arrangements. These assemblies self-construct three-dimensional thermally conductive networks through ANF gelation precipitation, which was analyzed as the key parameter for the realization of high thermal performances. The as-prepared ND@PDDA/ANF composite films exhibited high in-plane and through-plane TCs up to 30.99 and 6.34 W/m·K, respectively, at a 50 wt % functionalized ND loading, representing the optimal values among all previously reported polymer-based electrical insulating composite films. Furthermore, the nanocomposites also achieved other properties necessary for realistic applications, such as outstanding mechanical properties, excellent thermal stability, ultra-low thermal expansion coefficient, excellent electrical insulation, low dielectric constant, low dielectric loss, and outstanding flame retardancy. Thus, this excellent comprehensive performance enables the ND@PDDA/ANF composite films to be used as advanced multifunctional nanocomposites in thermal management, flexible electronics, and intelligent wearable equipment.

Postoperative ctDNA detection predicts relapse but has limited effects in guiding adjuvant therapy in resectable stage I NSCLC.

Background: To date, identifying resectable stage I non-small cell lung cancer (NSCLC) patients likely to benefit from adjuvant therapy (ADT) remains a major challenge. Previous studies suggest that circulating tumor DNA (ctDNA) is emerging as a promising biomarker for NSCLC. However, the effectiveness of ctDNA detection in guiding ADT for resectable stage I NSCLC patients remains elusive. This study aimed to elucidate the role of ctDNA detection in estimating prognosis and guiding ADT for resectable stage I NSCLC patients. Methods: Individual patient data and ctDNA results data were collected from 270 patients across four independent cohorts. The detection of ctDNA was conducted at 3 days to 1 month after surgery. The endpoint for this study was relapse-free survival (RFS) and overall survival (OS). Results: Of the 270 resectable stage I NSCLC patients, 9 patients with ctDNA-positive and 261 patients with ctDNA-negative. We found that the risk of recurrence was significantly lower in the ctDNA-negative group compared to the ctDNA-positive group(HR=0.11, p<0.0001). However, there is no difference in the risk of death between the two groups (p =0.39). In the ctDNA-positive group, there were no significant differences in RFS between patients who received ADT and patients who did not receive ADT (p =0.58). In the ctDNA-negative group, those who received ADT had a worse RFS in comparison with those who did not receive ADT (HR=2.36, p =0.029). No difference in OS was seen between patients who received ADT and patients who did not receive ADT in both the ctDNA-positive group and the ctDNA-negative group (All p values>0.05). Furthermore, there was no difference in RFS and OS between patients who received chemotherapy-based or tyrosine kinase inhibitor-based ADT and patients who did not receive ADT in both the ctDNA-positive group and the ctDNA-negative group (All p values>0.05). Conclusions: Postoperative ctDNA detection can be a prognostic marker to predict recurrence but has limited effects in guiding ADT for resectable stage I NSCLC. Future prospective investigations are needed to verify these results.

Non-collinear magnetic configuration mediated exchange coupling at the interface of antiferromagnet and rare-earth nanolayers.

Mn[Formula: see text]Ir/CoFe bilayer is a prototypical exchange-coupled antiferromagnet (AF)-ferromagnet (FM) system. Nevertheless, a strong exchange coupling between FM and rare-earth(RE) interfaces of Fe/Dy and Fe/Tb has been established earlier. Strong coupling at the FM-RE interface originates from the number of irreversible spins owing to the imbalance in the non-collinear configuration in RE. However, exchange coupling between AF-RE could not be established due to the minimal number of irreversible spins in AF and RE. A frustrated inter-domain magnetic interaction leads to the coexistence of spin-freezing-like ordering around the temperature range of helical spin modulation at the exchange-coupled interfaces of RE-based specimens. To overcome the lack of coupling between the AF-RE interface, we use a sandwich structure of AF-FM-RE layers (Mn[Formula: see text]Ir/CoFe/Dy) as we demonstrate establishing considerable exchange bias in the system. Changing the bias direction during field cooling introduces possible differences in non-collinear directions (helicities), which affects the number of irreversible spins and consequent exchange coupling differently for opposite directions. The non-collinear structures in RE are topologically stable; thus, their directions of orientation can be regarded as an additional degree of freedom, which can be manipulated in all-spin-based technology.