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• PLGA NPs were used as templates to prepare hollow MnO 2 NPs. • The CD47 protein on PLTM protected the NPs from elimination by the immune system. • P-selectin acted as a targeting ligand to achieve active targeting to tumors. • NPs underwent degradation in tumor to realize drug release and obtaining Mn2+. • Mn2+ acted as MRI agent and Fenton-like ions to convert endogenous H 2 O 2 to HO. In this study, platelet membrane (PLTM) biomimetic hollow MnO 2 nanoparticles were prepared and these were investigated for delivery of bufalin. Additionally, these nanoparticles, in response to the tumor microenvironment, showed rapid drug release and generated the hydroxyl radicals (HO) by the Fenton reaction between Mn2+ and endogenous H 2 O 2 for use in MRI-guided anti-tumor activity. Firstly, poly(lactic-co-glycolic acid) (PLGA) nanoparticles were used to reduce KMnO 4 to HMnO 2 nanoparticles followed by acetone etching. After bufalin loading, these NPs were biomimetically cloaked with PLTM to form PLTM-HMnO 2 @Bu NPs. In vitro release profiles showed that the NPs responded to acid pH and glutathione (GSH) to induce decomposition of MnO 2 , resulting in rapid release of bufalin and yielding the MRI contrast agent Mn2+. In vivo MRI studies revealed an obvious T 1 contrast enhancement at the tumor site because of a combination of the EPR and active targeting effects. The PLTM-HMnO 2 NPs led to effective inhibition of tumor growth, attributing to Fenton-like Mn2+ conversion of endogenous H 2 O 2 in the tumor to highly toxic HO and this anti-tumor efficacy was enhanced when combined with chemotherapy. These results indicate that the PLTM biomimetic HMnO 2 nanoparticles are promising drug delivery systems for MRI-monitoring and enhanced targeted treatment of tumors. [ABSTRACT FROM AUTHOR]

Compared with traditional chemotherapeutics, vascular disruption agents (VDAs) have the advantages of rapidly blocking the supply of nutrients and starving tumors to death. Although the VDAs are effective under certain scenarios, this treatment triggers angiogenesis in the later stage of therapy that frequently leads to tumor recurrence and treatment failure. Additionally, the nonspecific tumor targeting and considerable side effects also impede the clinical applications of VDAs. Here we develop a customized strategy that combines a VDA with an anti-angiogenic drug (AAD) using mesoporous silica nanoparticles (MSNs) coated with platelet membrane for the self-assembled tumor targeting accumulation. The tailor-made nanoparticles accumulate in tumor tissues through the targeted adhesion of platelet membrane surface to damaged vessel sites, resulting in significant vascular disruption and efficient anti-angiogenesis in animal models. This study demonstrates the promising potential of combining VDA and AAD in a single nanoplatform for tumor eradication.

Exosomes are membrane-bound nano-vehicles shed by most eukaryotic cells. Exosomes contain specific proteins and RNAs from parent cells, and they play key signaling roles in cellular development, modulation, and tissue regeneration. Attempts to isolate and modify exosomes to increase their targeting efficiency to specific tissue are still in their infancy. Here, we describe generation of exosomes from biopsy, isolation of exosomes by centrifugal ultrafiltration method, and approaches for manipulation of cardiac homing exosomes by chemical engineering for the treatment of myocardial infarction.

Hyperbaric oxygenation (HBO) for correction of platelet haemostasis disorders in coronary heart disease (CHD) is reasonable due to the associated hypocoagulation. However, in practice, the baseline state of platelet activity is not considered when prescribing HBO therapy. Available publications lack information on structural changes in the platelet membrane associated with the of phospholipase A2 (PLA2) activity, and on the HBO effect on the various steps of hemostasis., Objective: To study changes in serum PLA2 concentration and its relation to platelet aggregation activity during HBO in patients with stable CHD., Material and Methods: We examined 42 patients with stable angina FC II-III, 27 received antiplatelet therapy (Cardiomagnyl 75 mg: acetylsalicylic acid + magnesium hydroxide), and 15 patients did not. All patients received a 10-day course of HBO at 1.2 atmosphere mode for 40 min. Platelet hemostasis and serum PLA2 concentration were evaluated. Platelet aggregation was tested using Biola LA-230-2 aggregation analyzer (Biola Scientific, Russia). The platelets count and mean platelet volume (MPV) were determined on a Mindray BS-3200 hematology analyzer (Mindray, China). PLA2 levels were determined by enzyme immunoassay using Model 680 microplate reader (Bio-Rad, USA). Residual platelet reactivity was evaluated by 5.0 ADP-induced aggregation., Results: Assessment of the HBO effect on the functional state of platelets depending on their aggregation activity and the therapy taken showed a significant increase in spontaneous aggregation and ADP-induced aggregation at inducer concentration of 1.0 μM ( p =0.049) in patients with baseline hyperaggregation taking Cardiomagnyl after HBO. No significant changes in PLA2 concentration were observed. At the same time, patients with baseline hyperaggregation who did not take antiplatelet agents had no changes in platelet aggregation activity and a decreased serum PLA2. In patients with baseline normal aggregation receiving an antiplatelet drug, a course of HBO had no effect on platelet aggregation activity and PLA2 level. In patients with baseline normal aggregation who did not take antiplatelet agents, a course of HBO resulted in significant decrease in PLA2 levels and no changes in platelet aggregation activity. In patients with low aggregation activity (hypoaggregation) who took antiplatelet agents, a significant increase in spontaneous aggregation and no change of serum PLA2 after an HBO course was observed., Conclusion: The study showed a divergent response to the hyperbaric oxygen, depending on the antiplatelet therapy and the background aggregation.

The restriction of a tumor's energy supply is proven to be an effective means of treatment. Glucose oxidase (GOx), an enzyme that catalyzes the conversion of glucose to glucolactone, producing oxygen and hydrogen peroxide in the process, has proved useful in this regard. However, hypoxia, which is implicated in tumor growth, has been found to mediate resistance to this type of tumor starvation. Here, we describe the design and testing of a platelet membrane mimetic, PMS, consisting of mesoporous silica nanoparticles (MSNs) loaded with metformin (MET) as an inner layer and platelet membranes (PM) as an outer layer that inhibits oxygen consumption by the tumor cells' respiratory pathways and enhances the effectiveness of GOx. MET directly inhibits the activity of complex I in mitochondrial electron transport and is thus a potent inhibitor of cell respiration. PMS target tumor tissue effectively and, once internalized, MET can inhibit respiration. When oxygen is plentiful, GOx promotes glucose consumption, allowing amplification of its effects on tumor starvation. This combination of respiratory suppression by PMS and starvation therapy by GOx has been found to be effective in both targeting tumors and inhibiting their growth. It is hoped that this strategy will shed light on the development of next-generation tumor starvation treatments., (Copyright © 2020 Huang, Zhu, Chen, Huang, Li, Ding, Xia, Jiang and Li.)

Although cancer immunotherapy has emerged as a tremendously promising cancer therapy method, it remains effective only for several cancers. Photoimmunotherapy (e.g., photodynamic/photothermal therapy) could synergistically enhance the immune response of immunotherapy. However, excessively generated immunogenicity will cause serious inflammatory response syndrome. Herein, biomimetic magnetic nanoparticles, Fe 3 O 4 -SAS @ PLT, are reported as a novel approach to sensitize effective ferroptosis and generate mild immunogenicity, enhancing the response rate of non-inflamed tumors for cancer immunotherapy. Fe 3 O 4 -SAS@PLT are built from sulfasalazine (SAS)-loaded mesoporous magnetic nanoparticles (Fe 3 O 4 ) and platelet (PLT) membrane camouflage and triggered a ferroptotic cell death via inhibiting the glutamate-cystine antiporter system X c - pathway. Fe 3 O 4 -SAS @ PLT-mediated ferroptosis significantly improves the efficacy of programmed cell death 1 immune checkpoint blockade therapy and achieves a continuous tumor elimination in a mouse model of 4T1 metastatic tumors. Proteomics studies reveal that Fe 3 O 4 -SAS @ PLT-mediated ferroptosis could not only induce tumor-specific immune response but also efficiently repolarize macrophages from immunosuppressive M2 phenotype to antitumor M1 phenotype. Therefore, the concomitant of Fe 3 O 4 -SAS @ PLT-mediated ferroptosis with immunotherapy are expected to provide great potential in the clinical treatment of tumor metastasis., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Zirconia nanoparticles (ZrO2 NPs) are widely applied in the field of biomedicine. In this study, we constructed a nanoplatform of ZrO2 NPs coated with a platelet membrane (PLTm), named PLT@ZrO2. PLTm nanovesicles camouflage ZrO2 NPs, prevent nanoparticles from being cleared by macrophage, and target tumor sites. Compared to ZrO2 alone, PLT@ZrO2 is better at inhibiting the invasion and metastasis of Hela cells in vitro and in vivo. In vitro , PLT@ZrO2 inhibited the growth and proliferation of Hela cells. Scratch-wound healing recovery assay demonstrated that PLT@ZrO2 inhibited Hela cells migration. Transwell migration and invasion assays showed that PLT@ZrO2 inhibited Hela cells migration and invasion. In vivo , PLT@ZrO2 inhibited the tumor growth of Xenograft mice and inhibited the lung and liver metastasis of Hela cells. Immunofluorescence and Western blotting results showed that anti-metastasis protein (E-cadherin) was upregulated and pro-metastasis proteins (N-cadherin, Smad4, Vimentin, E-cadherin,β-catenin, Fibronectin, Snail, Slug, MMP2, Smad2) were down-regulated. Our study indicated that PLT@ZrO2 significantly inhibits tumor growth, invasion, and metastasis., (Copyright © 2020 Shang, Wang, Li, Zhao, Huang, Dong, Liu, Gui and Nie.)