Bacterial Metabolism-Initiated Nanocatalytic Tumor Immunotherapy

The low immunogenicity of tumors remains one of the major limitations of cancer immunotherapy.Herein,we report a bacterial metabolisminitiated and photothermal-enhanced nanocatalytic therapy strategy to completely eradicate primary tumor by triggering highly effective antitumor immune responses.Briefly,a microbiotic nanomedicine,designated as Cu_(2)O@ΔSt,has been constructed by conjugating PEGylated Cu_(2)O nanoparticles on the surface of an engineered Salmonella typhimurium strain(ΔSt).Owing to the natural hypoxia tropism ofΔSt,Cu_(2)O@ΔSt could selectively colonize hypoxic solid tumors,thus minimizing the adverse effects of the bacteria on normal tis-sues.Upon bacterial metabolism within the tumor,Cu_(2)O@ΔSt generates H_(2)S gas and other acidic substances in the tumor microenvironment(TME),which will in situ trigger the sulfidation of Cu_(2)O to form CuS facilitating tumor-specific photothermal therapy(PTT)under local NIR laser irradiation on the one hand.Meanwhile,the dissolved Cu+ions from Cu_(2)O into the acidified TME enables the nanocatalytic tumor therapy by catalyzing the Fenton-like reaction of decom-posing endogenous H_(2)O_(2) into cytotoxic hydroxyl radicals(·OH)on the other hand.Such a bacterial metabolism-triggered PTT-enhanced nanocatalytic treatment could effectively destroy tumor cells and induce a massive release of tumor antigens and damage-associated molecular patterns,thereby sensitizing tumors to checkpoint blockade(ICB)therapy.The combined nanocatalytic and ICB therapy results in the much-inhibited growth of distant and metastatic tumors,and more importantly,induces a powerful immunological memory effect after the primary tumor ablation.

二维MXene相Ti_3C_2高效氧还原电催化剂的制备和性能研究（英文）

二维MXene材料,由于具有良好的导电性和丰富的表面化学性质,在电催化领域具有广泛的应用前景,但在电催化氧还原领域鲜有报道.本文通过HF酸刻蚀和TPAOH插层两步法,用MAX陶瓷制备了具有二维层状结构的MXene相Ti_3C_2材料,并将其用作氧还原电催化剂.制备的二维Ti_3C_2材料厚度为0.5–2.0 nm,表明该材料的层数为1～2层. CV、LSV、RRDE等测试表明,二维Ti_3C_2材料具有良好的ORR性能和稳定性.

Soft-to-hard templating 到经由一个壶碳 / 硅石来源 copolymerization 的分散得好的做 N 的 mesoporous 碳 nanospheres

这里，我们报导一条新途径为很好驱散的做 N 的 mesoporous 碳 nanospheres (MCN ) 的合成经由碳来源(多巴胺) 和硅石来源(tetraethyl orthosilicate ) 的 copolymerization 作为 soft-to-hard templating 策略参考了，它为电气化学的 supercapacitor 展出高效。这个方法分别地克服不受管束的 dispersity 和软模板或难模板的方法的复杂过程的缺点。而且，综合 MCN 特征在一个壶合成期间由高贵金属的 nanoparticles 充实 heteroatom 做 N 和容易的 functionalization。所有上述字符在许多应用程序使同样准备的 MCN 成为一个有希望的平台。表明综合做氮的 MCN 的适用性，这材料为高效的电气化学的 supercapacitor 作为一个电极被采用了，它显示出 223 和 140 的一个电容 ? 在 0.5 和 10 的当前的密度的 F/g ? 在 1 的 A/g ? mol/L KOH 电解质分别地。

Starvation-Sensitized and Oxygenation-Promoted Tumor Sonodynamic Therapy by a Cascade Enzymatic Approach

The therapeutic outcomes of noninvasive sonodynamic therapy(SDT)are always compromised by tumor hypoxia,as well as inherent protective mechanisms of tumor.Herein,we report a simple cascade enzymatic approach of the concurrent glucose depletion and intratumoral oxygenation for starvation-sensitized and oxygenation-amplified sonodynamic therapy using a dual enzyme and sonosensitizer-loaded nanomedicine designated as GOD/CAT@ZPF-Lips.In particular,glucose oxidase-(GOD-)catalyzed glycolysis would cut off glucose supply within the tumor,resulting in the production of tumor hydrogen peroxide(H_(2)O_(2))while causing tumor cells starvation.The generated H_(2)O_(2)could subsequently be decomposed by catalase(CAT)to generate oxygen,which acts as reactants for the abundant singlet oxygen(^(1 O_(2))production by loaded sonosensitizer hematoporphyrin monomethyl ether(HMME)upon the US irradiation,performing largely elevated therapeutic outcomes of SDT.In the meantime,the severe energy deprivation enabled by GOD-catalyzed glucose depletion would prevent tumor cells from executing protective mechanisms to defend themselves and make the tumor cells sensitized and succumbed to the cytotoxicity of^(1 O_(2)).Eventually,GOD/CAT@ZPF-Lips demonstrate the excellent tumoral therapeutic effect of SDT in vivo without significant side effect through the cascade enzymatic starvation and oxygenation,and encouragingly,the tumor xenografts have been found completely eradicated in around 4 days by the intravenous injection of the nanomedicine without reoccurrence for as long as 20 days.

Generic synthesis and versatile applications of molecularly organic-inorganic hybrid mesoporous organosilica nanoparticles with asymmetric Janus topologies and structures

Precise control over the morphology,nanostructure,composition,and particle size of molecularly organic-inorganic hybrid mesoporous organosilica nanoparticles （MONs） still remains a major challenge,which severely restricts their broad applications.In this work an efficient bridged organic group-determined growth strategy has been proposed for the facile synthesis of highly dispersed and uniform MONs with multifarious Janus morphologies,nanostructures,organic-inorganic hybrid compositions,and particle sizes,which can be easily controlled simply by varying the bridged organic groups and the concentration of bis-silylated organosilica precursors used in the synthesis.In addition,the formation mechanism of Janus MONs determined by the bridged organic group has been discussed.Based on the specific structures,compositions,and asymmetric morphologies,all the synthesized Janus MONs with hollow structures （JHMONs） demonstrate excellent performances in nanomedicine as desirable drug carriers with high drug-loading efficiencies/capacities,pH-responsive drug releasing,and enhanced therapeutic efficiencies,as attractive contrastenhanced contrast agents for ultrasound imaging,and as excellent bilirubin adsorbents with noticeably high adsorption capacities and high blood compatibilities.The developed versatile synthetic strategy and the obtained JHMONs are extremely important in the development and applications of MONs,particularly in the areas of nanoscience and nanotechnology.

Nanomedicine-Leveraged Intratumoral Coordination and Redox Reactions of Dopamine for Tumor-Specific Chemotherapy

Great efforts have been made in investigating the neurotoxicity of dopamine(DA)in the presence of manganous ions.In contrast,here,we probe the possibility of DA-based cancer chemotherapy by leveraging intratumoral redox reactions of DA for producing cytotoxic species in situ.For this purpose,we have constructed a Mn-engineered,DA-loaded nanomedicine.Based on the unique size effect of the nanocarrier,this nanomedicine will not enter the central nervous system but can effectively accumulate in the tumor region,after which the nanocarrier can degrade to release Mn^(2+)and DA in response to the mild acidic intracelluar microenvironment of cancer cells.DA can chelate Mn^(2+)to form a binary coordination complex,where the strong metal-ligand interaction significantly promotes electron delocalization and elevates the reducibility of Mn center,favoring two sequential one-electron oxygen reduction reactions forming H_(2)O_(2),which can be further converted into highly oxidizing ·OH under the cocatalysis by Mn^(2+)and intracellular Fe^(2+).Additionally,as a twoelectron oxidation product of DA ligand,DA-oquinone is potent in exhausting cellular sulfhydryl and depleting reduced glutathione,inhibiting the intrinsic antioxidative mechanism of cancer cells,finally triggering severe oxidative damages in a synergistic manner.It is expected that such a strategy of nanotechnology-mediated metal-ligand coordination and subsequent nontoxicity-to-toxicity transition of DA in tumor may provide a promising prospect for future chemotherapy design.