Broeritchie1336

With the development of magnetic manipulation technology based on magnetic nanoparticles (MNPs), scaffold-free microtissues can be constructed utilizing the magnetic attraction of MNP-labeled cells. The rapid in vitro construction and in vivo vascularization of microtissues with complex hierarchical architectures are of great importance to the viability and function of stem cell microtissues. Endothelial cells are indispensable for the formation of blood vessels and can be used in the prevascularization of engineered tissue constructs. Herein, safe and rapid magnetic labeling of cells was achieved by incubation with MNPs for 1 h, and ultrathick scaffold-free microtissues with different sophisticated architectures were rapidly assembled, layer by layer, in 5 min intervals. The in vivo transplantation results showed that in a stem cell microtissue with trisection architecture, the two separated human umbilical vein endothelial cell (HUVEC) layers would spontaneously extend to the stem cell layers and connect with each other to form a spatial network of functional blood vessels, which anastomosed with the host vasculature. The "hamburger" architecture of stem cell microtissues with separated HUVEC layers could promote vascularization and stem cell survival. This study will contribute to the construction and application of structural and functional tissues or organs in the future.Chemotherapy, as one of the most commonly used treatment modalities for cancer therapy, provides limited benefits to hepatoma patients, owing to its inefficient delivery as well as the intrinsic chemo-resistance of hepatoma. Bioinformatic analysis identified the therapeutic role of a liver-specific microRNA - miR-122 for enhancing chemo-therapeutic efficacy in hepatoma. Herein, a cyclodextrin-cored star copolymer nanoparticle system (sCDP/DOX/miR-122) is constructed to co-deliver miR-122 with doxorubicin (DOX) for hepatoma therapy. In this nanosystem, miR-122 is condensed by the outer cationic poly (2-(dimethylamino) ethyl methacrylate) chains of sCDP while DOX is accommodated in the inner hydrophobic cyclodextrin cavities, endowing a sequential release manner of miR-122 and DOX. The preferentially released miR-122 not only directly induces cell apoptosis by down regulation of Bcl-w and enhanced p53 activity, but also increases DOX accumulation through inhibiting cytotoxic efflux transporter expression, which realizes synergistic performance on cell inhibition. Moreover, sCDP/DOX/miR-122 displays remarkably increased anti-tumor efficacy in vivo compared to free DOX and sCDP/DOX alone, indicating its great promising in hepatoma therapy.Extracellular vesicles (EV) are lipid-bilayer enclosed vesicles in submicron size that are released from cells. A variety of molecules, including proteins, DNA fragments, RNAs, lipids, and metabolites can be selectively encapsulated into EVs and delivered to nearby and distant recipient cells. In tumors, through such intercellular communication, EVs can regulate initiation, growth, metastasis and invasion of tumors. Recent studies have found that EVs exhibit specific expression patterns which mimic the parental cell, providing a fingerprint for early cancer diagnosis and prognosis as well as monitoring responses to treatment. Accordingly, various EV isolation and detection technologies have been developed for research and diagnostic purposes. Moreover, natural and engineered EVs have also been used as drug delivery nanocarriers, cancer vaccines, cell surface modulators, therapeutic agents and therapeutic targets. Overall, EVs are under intense investigation as they hold promise for pathophysiological and translational discoveries. This comprehensive review examines the latest EV research trends over the last five years, encompassing their roles in cancer pathophysiology, diagnostics and therapeutics. This review aims to examine the full spectrum of tumor-EV studies and provide a comprehensive foundation to enhance the field. The topics which are discussed and scrutinized in this review encompass isolation techniques and how these issues need to be overcome for EV-based diagnostics, EVs and their roles in cancer biology, biomarkers for diagnosis and monitoring, EVs as vaccines, therapeutic targets, and EVs as drug delivery systems. We will also examine the challenges involved in EV research and promote a framework for catalyzing scientific discovery and innovation for tumor-EV-focused research.More and more studies have recognized that the nanosized pores of hydrogels are too small for cells to normally grow and newly formed tissue to infiltrate, which impedes tissue regeneration. Recently, hydrogels with macropores and/or controlled degradation attract more and more attention for solving this problem. Sodium alginate/Bioglass (SA/BG) hydrogel, which has been reported to be an injectable and bioactive hydrogel, is also limited to be used as tissue engineering scaffolds due to its nanosized pores. Therefore, in this study, degradation of SA/BG hydrogel was modulated by grafting deferoxamine (DFO) to SA. The functionalized grafted DFO-SA (G-DFO-SA) was used to form G-DFO-SA/BG injectable hydrogel. In vitro degradation experiments proved that, compared to SA/BG hydrogel, G-DFO-SA/BG hydrogel had a faster mass loss and structural disintegration. When the hydrogels were implanted subcutaneously, G-DFO-SA/BG hydrogel possessed a faster degradation and better tissue infiltration as compared to SA/BG hydrogel. MYF-01-37 ic50 In addition, in a rat full-thickness skin defect model, wound healing studies showed that, G-DFO-SA/BG hydrogel significantly accelerated wound healing process by inducing more blood vessels formation. Therefore, G-DFO-SA/BG hydrogel can promote tissue infiltration and stimulate angiogenesis formation, which suggesting a promising application potential in tissue regeneration.The immunosuppressive tumor microenvironment (TME) of cancer strongly hinders the anti-tumor immune responses, thereby resulting in disappointing responses to immunotherapy. Chemoattractive and promotive traits of chemokines exerted on leukocytes have garnered interest in improving the efficiency of immunotherapy by increasing the infiltration of immune cells in the TME. In this study, a folic acid (FA) -modified gene delivery system based on the self-assembly of DOTAP, MPEG-PCL-MPEG, and FA-PEG-PCL-PEG-FA, namely F-PPPD, was developed to deliver plasmids encoding the immunostimulating chemokine CKb11. The delivery of plasmid CKb11 (pCKb11) by F-PPPD nanoparticles resulted in the high secretion of CKb11 from tumor cells, which successfully activated T cells, suppressed the M2 polarization of macrophages, promoted the maturation of dendritic cells (DCs), facilitated the infiltration of natural killer (NK) cells and inhibited the infiltration of immunosuppressive cells in tumor tissues. Administration of F-PPPD/pCKb11 also significantly suppressed the cancer progression.