A Novel CaCu-Metal-Organic-Framework Based Multimodal Treatment Platform for Enhanced Synergistic Therapy of Hepatocellular Carcinoma.

Metal ions have attracted a lot of interest in antitumor therapy due to their unique mechanism of action. However, multiple death mechanisms associate with metal ions to synergistic antitumors have few studies mainly due to the serious challenges in designing and building metal-associated multimodal treatment platforms. Hence, a series of glutathione-activatable CaCu-based metal-organic-frameworks loaded with doxorubicin and ovalbumin are successfully designed and synthesized with an "all in one" strategy, which is modified by galactosamine-linked hyaluronic acid to prepare multimodal treatment platform (SCC/DOX@OVA-HG) for targeted delivery and synergistic antitumor therapy. SCC/DOX@OVA-HG can be rapidly degraded by the overexpressed glutathione and then releases the "cargoes" in the tumor microenvironment. The released Cu+ efficiently catalyzes H2O2 to produce highly toxic ROS for CDT, and the up-regulation of calcium ion concentration in tumor cells induced by the released Ca2+ enables calcium overload therapy, which synergically enhances the metal-related death pattern. Meanwhile, OVA combined with Ca2+/Cu2+ further activates macrophages into an M1-like phenotype to accelerate tumor cell death through immunotherapy. Besides, the released DOX can also insert into the DNA double helix for chemotherapy. Consequently, the developed SCC/DOX@OVA-HG reveals significantly improved antitumor efficacy through a multimodal synergistic therapy of chemotherapy, chemodynamic therapy, calcium overload, and immunotherapy.

A Purposefully Designed pH/GSH-Responsive MnFe-Based Metal-Organic Frameworks as Cascade Nanoreactor for Enhanced Chemo-Chemodynamic-Starvation Synergistic Therapy.

Metal-organic frameworks (MOFs) have emerged as promising novel therapeutics for treating malignancies due to their tunable porosity, biocompatibility, and modularity to functionalize with various chemotherapeutics drugs. However, the design and synthesis of dual-stimuli responsive MOFs for controlled drug release in tumor microenvironments are vitally essential but still challenging. Meanwhile, the catalytic effect of metal ions selection and ratio optimization in MOFs for enhanced chemodynamic therapy (CDT) is relatively unexplored. Herein, a series of MnFe-based MOFs with pH/glutathione (GSH)-sensitivity are synthesized and then combined with gold nanoparticles (Au NPs) and cisplatin prodrugs (DSCP) as a cascade nanoreactor (SMnFeCGH) for chemo-chemodynamic-starvation synergistic therapy. H+ and GSH can specifically activate the optimal SMnFeCGH nanoparticles in cancer cells to release Mn2+/4+ /Fe2+/3+ , Au NPs, and DSCP rapidly. The optimal ratio of Mn/Fe shows excellent H2 O2 decomposition efficiency for accelerating CDT. Au NPs can cut off the energy supply to cancer cells for starvation therapy and strengthen CDT by providing large amounts of H2 O2 . Then H2 O2 is catalyzed by Mn2+ /Fe2+ to generate highly toxic •OH with the depletion of GSH. Meanwhile, the reduced DSCP accelerates cancer cell regression for chemotherapy. The ultrasensitivity cascade nanoreactor can enhance the anticancer therapeutic effect by combining chemotherapy, CDT, and starvation therapy.

[Application of Qu single abdominal aorta clamping for bloodless hepatectomy and Pringle hepatectomy in 118 cases of liver tumors].

OBJECTIVE: To compare the results of application of Qu single abdominal aorta clamping for bloodless hepatectomy and Pringle hepatectomy in 118 cases of liver tumors. METHODS: The clinical data of 118 patients, including 59 patients undergoing Qu single abdominal aorta clamping for bloodless hepatectomy (Group QG) and 59 patients undergone Pringle first hepatic portal clamping hepatectomy (Group PG) since March 2009 in the Ningbo Tumor Hospital and Jiangxi Provincial Hospital were retrospectively reviewed. The changes of blood pressure, oxygen saturation, urine volume, intravenous fluid volume, amount of bleeding, time of abdominal aorta (or first hepatic portal) clamping, duration of operation and anesthesia, and other intraoperative indexes of the two groups were compared, and the changes of peritoneal drainage, blood tests, liver functions, etc. before operation and 1, 3, 7, 14 days after the hepatectomy in the two groups were also analyzed. RESULTS: After taking appropriate measures for intraoperative blood pressure control, only small fluctuations of blood pressure, which could be safely adjusted and controlled with stable vital signs, was observed in the group QG. The amount of intraoperative bleeding in the group QG was (96.25 ± 18.45) ml, significantly less than (536.25 ± 35.65) ml in the group PG (P < 0.05). In the group QG, both the duration of operation time [(227.58 ± 28.20) min] and duration of anesthesia [(249.48 ± 31.35) min] were significantly shorter than that [(261.46 ± 32.12) min and (286.58 ± 35.62) min, respectively] in the group PG (both P < 0.05). The postoperative liver dysfunction in the group QG was also milder than that in the group PG (P < 0.05). CONCLUSIONS: For liver tumor patients, Qu single abdominal aorta clamping for bloodless hepatectomy can basically achieve the goal of bloodless hepatectomy. This surgical operation is simple and safe, worthy of recommendation to skillful liver surgeons in hospitals there are some difficulties of blood supply.