Latest ArticlesAs a worldwide public health issue, chronic kidney disease still lacks of effective therapeutic approaches due to the challenges in conventional organ transplantation and dialysis. Renal tissue engineering offers an advantageous therapeutic or regenerative option over typical donor organ. However, despite the great progress of decellularized extracellular matrix based scaffold for the renal regeneration, several safety concerns and complex composition still remain to be addressed. Herein, the extracellular matrix-mimicking hydrogel scaffolds were developed through covalent and physical cross-linking between swim bladder-derived natural collagen (COL) and anti-fibrosis chondroitin sulfate (CS) derivatives. The biomimetic hydrogels showed proper mechanical property, excellent thermal stability and high biocompatibility both in vitro and in vivo, by altering the mass ratio of COL and CS. When implanted in partially nephrectomized rat model, the 1COL/2CS scaffold enable it recruit more native kidney cells, reduce the tubular damage, and even induce the regeneration of renal tubular-like tissue and restore renal metabolic function more effectively comparing with the pure 2COL and 2CS scaffold. These results suggest that the biomimetic scaffold is a promising functional platform for treating renal diseases.
Photodynamic therapy (PDT) has emerged as a potential clinical strategy for tumor therapy. It can generate reactive oxygen species (ROS) to cause the chemical damage of tumor cells and promote the immune killing effects of T cells on tumor cells in the presence of enough oxygen and PDT drugs. However, most solid tumors are in a state of oxygen deficiency, which seriously limit the efficacy of PDT in generation enough ROS. Besides, few safe PDT drugs with ideal pharmacokinetic behavior are available in the clinic, which severely limits the clinical transformation and application of PDT. Herein, we utilized manganese chloride to mineralize the hydrophilic indocyanine green/albumin polyplexes (ICG@BSA@MnO2) by using bio-mineralized method to solve these problems of PDT. These ICG@BSA@MnO2 nanoparticles could circulate in the blood for a long period other than quickly removed from body after 30 min like free ICG. When accumulated at the tumor site, ICG was responsively released in the presence of hydrogen peroxide. Apart this, the tumor hypoxia microenvironment was also reversed owing to enhanced O2 generation by the reaction of MnO2 with hydrogen peroxide. Benefits from the rich accumulation of ICG and ameliorated tumor hypoxia in the tumor sites, the enhanced generation of ROS could successfully promote the distribution of CD3+ and CD8+ T cells inside the tumors, which then lead to the amplified efficacy of PDT in both CT26 and B16F10 tumor models without causing any side effects.
Using nanoparticle-based drug delivery systems as enhancers is a robust strategy for transdermal delivery; however, the mechanisms by which these systems promote transdermal penetration are still unclear. Here, we fabricated a dual-labeled nano drug delivery system that allows discrete visualization of both the drug and the nanoparticle carrier. To comprehensively examine its potential mechanism, we investigated its effects on human epidermal keratinocyte HaCaT cells, including changes in cell membrane potential, intracellular Ca2+ concentration, and Ca2+-ATPase activity. P-glycoprotein (P-gp) expression in nanoparticle-treated human dermal microvascular endothelial cells was detected by western blotting and immunofluorescence. Furthermore, the transdermal absorption and biodistribution of the dual-labeled nanoparticles were deeply investigated by skin permeability study in vitro and in vivo using fluorescence microscopy and in vivo imaging, respectively. In addition to reducing membrane potential, increasing the intracellular Ca2+ concentration, and decreasing Ca2+-ATPase activity, our results indicate that the dual-labeled nanoparticles can downregulate P-gp to promote transdermal absorption. Fluorescence and in vivo imaging visually demonstrated that the nanoparticle delivery system penetrated into the dermis through the stratum corneum. All these results indicate that this dual-labeled nano delivery system provides a new method for future in-depth visual explorations of transdermal drug delivery mechanisms.
Oncolytic virus is an emerging anti-cancer strategy. However, extracellular matrix (ECM), as a physical barrier, limits virus spread within the tumor. To overcome the obstacle, we constructed a recombinant Newcastle disease virus (NDV) expressing matrix metalloproteinase (MMP8) (NDV-MMP8) using with reverse genetic technology. In vitro, NDV-MMP8 was identified and verified by WB and ELISA. Cell viability was detected by CCK-8 assay. In vivo, we established two liver cancer xenograft models. NDV-MMP8 was injected into the tumor to observe the tumor volume and survival of mice. The changes in extracellular matrix were observed by Masson's trichrome staining. Virus expression in tumor tissues was detected by immunofluorescence assay. The virus titer in tumor tissues was detected by TCID50. Histopathological changes were detected by hematoxylin and eosin (HE) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. Intratumoral administration of NDV-MMP8 can effectively degrade ECM, promote the spread of the virus within the tumor, and reduce tumor growth rate. Therefore, the method of increasing intratumoral virus accumulation by degradation of the ECM to enhance the oncolytic effect has great potential for clinical application.
Palladium-catalyzed oxidative formal [4 + 1] annulation of pyridine-substituted acrylonitriles toward divergent fused N-heterocycles synthesis is reported. The heterodifunctionalization reaction with Cu(OAc)2 and urea as the nitrogen source accesses to nitrile-substituted pyrazolo[1, 5-a]pyridines in moderate to good yields, while the homodifunctionalization reaction with FeBr3 leads to synthesis of nitrile-substituted indolizines in excellent yields.
Pyridinium 1, 4-zwitterionic thiolates were applied to a formal [3 + 2] annulation reaction with modified activated alkynes, affording various tetrasubstituted thiophenes with aryl, alkenyl, alkyl or silyl group at the special position. The structural modification of alkyne substrates enabled the synthesis of diverse thiophenes to be achieved using the pyridinium 1, 4-zwitterionic thiolates as the sulfur-containing building blocks. This approach is metal-free and catalyst-free.
In situ formation of composite micro-mesoporous dendritic fibrous nano-silica (DFNS) and Al-DFNS was prepared using a cetylpyridinium bromide (CPB) template synthetic system. Dealumination is induced by impregnation of zirconium with flux followed by a sulfuric acid treatment. This procedure results in a series of highly uniform nano-spheres, which exhibit stronger acid property than that of Al-MCM-41. In the selective alkylation of anthracene with tert‑amyl alcohol, SO42− modified Zr-contained dealuminated Al-DFNS (SZ-DeAl-DFNS) shows great catalytic activity and higher conversion (60.8%). The DFNS samples were characterized with XRD, SEM, TEM, NH3-TPD and other techniques. The results reveal that DFNSs consist of center-radial micro-mesopores and that the acid contribution of SZ-DeAl-DFNS is much broader, as compared with amorphous aluminosilicate
Combined theoretical and experimental studies have explained the mechanism of Pd-catalyzed δ-C(sp3)−H arylation of primary amines. Instead of the monomeric Pd mechanism, our research unveils that all steps including C-H activation, oxidative addition, and reductive elimination take place via the heterodimeric Pd-Ag intermediates and transition states. Experimentally, the active heterodimeric Pd-Ag species were detected by mass spectrometry, which further confirms the proposed heterodimeric mechanism. Insight gained through this study reveals the synergistic manner of palladium catalysis and silver(I) additives in native NH2-directed C‒H activation and C-C coupling reactions.
Carbene transfer reactions play an important role in the field of organic synthesis because of their ability to construct a variety of molecules. Herein, we reported on blue light-induced cyclopropenizations of N-tosylhydrazones in water, which avoids the use of expensive metal-based catalysts and toxic organic solvents. This metal-free and operationally simple methodology enable highly efficient cyclopropenizations, X-H insertion reactions, and cyclopropanation under mild reaction conditions.
We report a facile and tailored method to prepare globally twisted chiral molecular cages through tunable coordination of bis-bipyridine-terminated helicene ligands to a series of transition metals including Fe(II), Co(II), Ni(II) and Zn(II). This system shows an efficient remote transfer of stereogenecity from the helicene core to the bipyridine-metal coordination sites and subsequently the entire cages. While the Fe(II), Co(II) and Ni(II)-derived M2L3 (M for metal and L for ligand) cages exhibit quasi-reversible redox features, the Zn(II) analogues reveal prominent yellow circularly polarized luminescence. Interestingly, with the addition of Na2SO4, the Zn2L3 cages reassemble into sextuple-stranded Zn6L6(SO4)4 cages in which three Zn2L2 units are bound together by four sulfates and further coalesced by offset inter-ligand π-π interactions.
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