Microwave-responsive gadolinium metal-organic frameworks nanosystem for MRI-guided cancer thermotherapy and synergistic immunotherapy.

The clinical application of cancer immunotherapy is unsatisfied due to low response rates and systemic immune-related adverse events. Microwave hyperthermia can be used as a synergistic immunotherapy to amplify the antitumor effect. Herein, we designed a Gd-based metal-organic framework (Gd-MOF) nanosystem for MRI-guided thermotherapy and synergistic immunotherapy, which featured high performance in drug loading and tumor tissue penetration. The PD-1 inhibitor (aPD-1) was initially loaded in the porous Gd-MOF (Gd/M) nanosystem. Then, the phase change material (PCM) and the cancer cell membrane were further sequentially modified on the surface of Gd/MP to obtain Gd-MOF@aPD-1@CM (Gd/MPC). When entering the tumor microenvironment (TME), Gd/MPC induces immunogenic death of tumor cells through microwave thermal responsiveness, improves tumor suppressive immune microenvironment and further enhances anti-tumor ability of T cells by releasing aPD-1. Meanwhile, Gd/MPC can be used for contrast-enhanced MRI. Transcriptomics data revealed that the downregulation of MSK2 in cancer cells leads to the downregulation of c-fos and c-jun, and ultimately leads to the apoptosis of cancer cells after treatment. In general, Gd/MPC nanosystem not only solves the problem of system side effect, but also achieves the controlled drug release via PCM, providing a promising theranostic nanoplatform for development of cancer combination immunotherapy.

Analysis of Developmental Characteristics and Dominant Factors of Pore-Fracture Systems in Lower Cambrian Marine Shale Reservoirs: A Case Study of the Niutitang Formation, Fenggang Block, Southern China.

Due to breakthroughs in the Lower Silurian Longmaxi Formation in the Sichuan Basin and multiple strata around the basin, the northern part of Guizhou adjacent to the Sichuan Basin has become a key area for shale gas exploration. Compared with the Longmaxi Formation, the Niutitang Formation displays greater TOC (total organic carbon) content, depositional thickness and distribution area, but the details remain undetermined. In the study area, the Lower Cambrian Niutitang Formation typically has high TOC content, maturity and brittle mineral content. The study area has experienced multiple periods of tectonic movement, which have great influence on the fracture and pore characteristics. The fractures are mainly structural fractures and have obvious zoning. The primary types of pores are intraparticle pores, organic matter pores, and interparticle pores. Further, macropores and mesopores less than 50 nm contribute most of the pore volume, while pores less than 2 nm contribute most of the specific surface area. Many factors affect the pore-fracture system, such as tectonism, TOC content, mineral composition, and sedimentary environment. Tectonic movements produce fractures based on the changing stress field, but the degree of fracture development does not agree well with the degree of pore development. The TOC content has good positive correlations with the development of fractures and micropores, especially for nanoporosity, while clay minerals show a negative correlation with the development of fractures but a strong positive correlation with the growth of micropores. Quartz displays a positive correlation with the development of fractures but no good correlation with pore development. Finally, the lithofacies, lithologies and mineral compositions under the control of sedimentary environments are internal factors that can impact the development of pore-fracture systems.

Amplified intracellular Ca2+ for synergistic anti-tumor therapy of microwave ablation and chemotherapy.

BACKGROUND: Developing new strategies to reduce the output power of microwave (MW) ablation while keeping anti-tumor effect are highly desirable for the simultaneous achievement of effective tumor killing and avoidance of complications. We find that mild MW irradiation can significantly increase intracellular Ca2+ concentration in the presence of doxorubicin hydrochloride (DOX) and thus induce massive tumor cell apoptosis. Herein, we designed a synergistic nanoplatform that not only amplifies the intracellular Ca2+ concentration and induce cell death under mild MW irradiation but also avoids the side effect of thermal ablation and chemotherapy. RESULTS: The as-made NaCl-DOX@PLGA nanoplatform selectively elevates the temperature of tumor tissue distributed with nanoparticles under low-output MW, which further prompts the release of DOX from the PLGA nanoparticles and tumor cellular uptake of DOX. More importantly, its synergistic effect not only combines thermal ablation and chemotherapy, but also obviously increases the intracellular Ca2+ concentration. Changes of Ca2+ broke the homeostasis of tumor cells, decreased the mitochondrial inner membrane potential and finally induced the cascade of apoptosis under nonlethal temperature. As such, the NaCl-DOX@PLGA efficiently suppressed the tumor cell progression in vivo and in vitro under mild MW irradiation for the triple synergic effect. CONCLUSIONS: This work provides a biocompatible and biodegradable nanoplatform with triple functions to realize the effective tumor killing in unlethal temperature. Those findings provide reliable solution to solve the bottleneck problem bothering clinics about the balance of thermal efficiency and normal tissue protection.

Ultrasound-guided percutaneous microwave ablation of central intraductal papilloma: a prospective pilot study.

Background: Central intraductal papilloma (IDP) has a low risk of cancer evolution; therefore, surgical treatment of IDP is controversial. We sought to validate ultrasound (US)-guided percutaneous microwave ablation (MWA) for minimally invasive treatment of IDP. Methods: Thirteen women with central IDP, including six with nipple discharge, underwent US-guided core needle biopsy and MWA from December 2016 to November 2017. Lesions histologically diagnosed as benign IDP were included. The hydro-dissection technique was used to protect the nipple during the entire ablation procedure. We evaluated and recorded data of complete ablation, volume reduction, and complications. Results: MWA was successfully performed in all patients, with 100% complete ablation, assessed by magnetic resonance imaging or contrast-enhanced US. Mean tumor size was 13.5 ± 4.1 (7.0-20.0) mm; the mean ablation time was 1.4 (0.7-10.3) min. At the median 13.7-month follow-up, mean lesion sizes at 3, 6, and 12 months after MWA were all significantly smaller than that at baseline. Total volume reduction rates were 52.3 ± 18.2% (range, 24.2-81.8%), 72.6 ± 23.1% (range, 39.4-95.9%), and 92.9 ± 7.5% (range, 75.0-100%) at 3-, 6-, and 12-month follow-up, respectively, with significant differences (p < .01). Three lesions with diameters 7 mm, 9 mm, and 12 mm disappeared completely at 3, 6, and 6 months after MWA, respectively, on US imaging. Nipple discharge disappeared immediately after MWA. Cosmetic effects were reported as excellent by all patients and no complications were observed. Conclusion: US-guided MWA of central IDP proved feasible and effective, with considerable volume reduction and satisfactory cosmetic outcomes.

Laser-Induced Antibacterial Activity of Novel Symmetric Carbazole-Based Ethynylpyridine Photosensitizers.

In this study, two kinds of novel carbazole-based ethynylpyridine salts: 3,6-bis[2-(1-methylpyridinium)ethynyl]-9-pentyl-carbazole diiodide (BMEPC) and 3,6-bis[2-(1-methylpyridinium)ethynyl]-9-methyl-carbazole diiodide (BMEMC) have been employed as photosensitizers owing to their excellent antibacterial activity. These molecules possess symmetric A-π-D-π-A-type structures, which would bring in the unique optical properties. The inhibition zone measurement of a gradient concentration from 0 to 100 µM showed BMEPC and BMEMC photoinduced antibacterial activity against Escherichia coli. Diameters of zone of inhibition were up to 15 and 14 mm under laser irradiations. Under the exposure of the laser of 442 nm with a power density of 20 mW/cm2, the minimum inhibitory concentrations (MICs) of BMEPC on E. coli were between 3.5 and 6.9 µM and that of BMEMC were between 9.4 and 18.8 µM, respectively. In the dark experiments as a control, the MIC value is between 6.9 and 13.8 µM for BMEPC, whereas it is between 187.5 and 225.0 µM for BMEMC. By the comparison of the MIC values of BMEPC and BMEMC with laser irradiation and in dark, the laser-induced toxicity on bacteria is more evident, though both of the derivatives have dark toxicity. With the laser irradiation duration of 30 s and 10 min for BMEPC and BMEMC, respectively, the survival rate of E. coli approximates zero. An antibacterial mechanism has been proposed based on the electron paramagnetic resonance characterization, which indicates that a nitride radical is generated under laser irradiation. The carbazole-based ethynylpyridine photosensitizers would provide high potential for further applications in photodynamic therapy.

Hollow nanospheres based on the self-assembly of alginate-graft-poly(ethylene glycol) and α-cyclodextrin.

This article studies the self-assembly of alginate-graft-poly(ethylene glycol) (Alg-g-PEG) and α-cyclodextrin (α-CD) in aqueous solution. It was found that they could form hollow spheres because of the formation of coil-rod Alg-g-PEG/α-CD inclusion complexes. In these Alg-g-PEG/α-CD complexes, the α-CDs are stacked along the PEG side chains to form a rod block, and alginate main chains act as a coil block. More rod-like blocks in Alg-g-PEG/α-CD favor the formation of small assemblies. The assemblies of Alg-g-PEG/α-CD show a dependence on concentration, temperature, pH, and salt concentration. At low concentration (below 0.125%) or high temperature (above 32 °C), Alg-g-PEG/α-CD particles were unstable and disrupted. Increasing the salt or decreasing the pH resulted in the aggregation of Alg-g-mPEG/α-CD particles, as detected by the increase in the recorded hydrodynamic diameter (D(h)).

Degradable hollow spheres based on self-assembly inclusion.

Degradable hollow nanospheres are prepared by self-assembly of rod-coil Alg-g-PEG/alpha-CD (Alginate-g-Poly(ethylene glycol)/alpha-Cyclodextrin) complexes in water, in which the rod-like segments were formed by inclusion between alpha-CDs and grafted PEG chains and the coil-like segments were protonated alginate backbones.