查看更多>>摘要：Bacterial outer membrane vesicles(OMVs)are potent immunostimulants of regulating the tumor microenvironment(TME)for immunotherapy,and can be used to deliver drugs.However,the severe systemic inflammatory response triggered by OMVs upon intravenous(i.v.)injection has limited their application.Here,we developed a safe and effective strategy by conjugating doxorubicin-loaded serum albumin(SA-DOX,AD)onto the surface of OMVs using a matrix metalloproteinase(MMP)-cleavable peptide linker(cL).This approach enabled the dynamic shielding of OMVs to reduce the systemic side effects while simultaneously enhancing the anti-tumor effects through chemo-immunotherapy.Specifically,the resulting OMV-cL-AD formulation exhibited significantly enhanced accumulation at the tumor site after i.v.administration,facilitated by the SA decoration on the OMVs surface.Subsequently,the shield on the OMV-cL-AD was cleaved by the over-expressed MMP in the TME,leading to the release of both OMVs and AD.This process provided OMV-induced immunotherapy and DOX-induced chemotherapy,resulting in synergistic tumor inhibition.In conclusion,our work demonstrated the potential of OMV-cL-AD as an effective immunochemotherapy strategy that can prolong the survival time of mice without inducing side effects.
查看更多>>摘要：Pancreatic cancer stands out as a recognized intractable tumor due to its high malignancy and mortality rates,which are largely attributed to the insensitivity of current clinical chemotherapies or multidrug-resistance.Combinatorial chemo and gene therapy that integrates different therapeutic targets,may increase the chemosensitivity of pancreatic cancer and synergistically enhance the antitumor efficacy.However,conventional co-delivery of gene and chemo drugs is intensively dependent on complex nanoparticle delivery systems,thus would be limited by unstable drug packaging,nonspecific biodistribution,and biosafety problem.Herein,we rationally designed an epidermal growth factor-receptor(EGFR)-targeted and gemcitabine-incorporated oligonucleotide(termed as chemogene)with anti-Bcl-2 sequence,which achieves simple and precise integration of gemcitabine into a gene regulative agent,as well as the EGFR-targeted delivery for pancreatic cancer therapy.Through solid-phase synthesis,gemcitabine,as the first-line chemodrug for pancreatic cancer,is introduced to the antisense oligonucleotide to replace all cytosine nucleosides to obtain the gemcitabine-integrated chemogene(Ge-ASOBcl-2).Thereafter,Ge-ASOBcl-2 is covalently coupled with EGFR nanobody to construct the final targeted chemogene without any exogenous carriers.Notably,this nanobody-conjugated chemogene exhibits remarkable tumor targeting capability and antitumor effects both in vitro and in vivo,which initiates a first step toward the application of combinatorial chemo and gene therapy for future pancreatic cancer treatment.
查看更多>>摘要：Parkinson's disease(PD)is a prevalent neurodegenerative disorder accompanied by movement disorders and neuroinflammatory injury.Anti-inflammatory intervention to regulate oxidative stress in the brain is beneficial for managing PD.However,traditional natural antioxidants have failed to meet the clinical treatment demands due to insufficient activity and sustainability.Herein,Cu-doping zeolite imidazolate framework-8(ZIF-8)nanozyme is designed to simulate Cu/Zn superoxide dismutase(SOD)by biomimetic mineralization.The nanozyme composite is then integrated into thermosensitive hydrogel(poly(lactic-co-glycolic acid)-poly(ethylene glycol)-poly(lactic-co-glycolic acid)(PLGA-PEG-PLGA))to form an effective antioxidant system(Cu-ZIF@Hydrogel).The thermosensitive hydrogel incorporating nanozymes demonstrate distinct viscoelastic properties aimed at enhancing local nanozyme adhesion,prolonging nanozyme retention time,and modulating antioxidant activity,thus significantly improving the bioavailability of nanozymes.At the cellular and animal levels of PD,we find that Cu-ZIF@Hydrogel bypass the blood-brain barrier and efficiently accumulate in the nerve cells.Moreover,the Cu-ZIF@Hydrogel significantly alleviate the PD's behavioral and pathological symptoms by reducing the neuroinflammatory levels in the lesion site.Therefore,the hydrogel-incorporating nanozyme system holds great potential as a simple and reliable avenue for managing PD.
查看更多>>摘要：Living photovoltaics are microbial electrochemical devices that use whole cell-electrode interactions to convert solar energy to electricity.The bottleneck in these technologies is the limited electron transfer between the microbe and the electrode surface.This study focuses on enhancing this transfer by engineering a polydopamine(PDA)coating on the outer membrane of the photosynthetic microbe Synechocystis sp.PCC6803.This coating provides a conductive nanoparticle shell to increase electrode adhesion and improve microbial charge extraction.A combination of scanning electron microscopy(SEM),transmission electron microscopy(TEM),UV-Vis absorption,and Raman spectroscopy measurements were used to characterize the nanoparticle shell under various synthesis conditions.The cell viability and activity were further assessed through oxygen evolution,growth curve,and confocal fluorescence microscopy measurements.The results show sustained cell growth and detectable PDA surface coverage under slightly alkaline conditions(pH 7.5)and at low initial dopamine(DA)concentrations(1 mM).The exoelectrogenicity of the cells prepared under these conditions was also characterized through cyclic voltammetry(CV)and chronoamperometry(CA).The measurements show a three-fold enhancement in the photocurrent at an applied bias of 0.3 V(vs.Ag/AgCl[3 M KCl])compared to non-coated cells.This study thus lays the framework for engineering the next generation of living photovoltaics with improved performances using biosynthetic electrodes.
查看更多>>摘要：Recent advances in coupling light-harvesting microorganisms with electronic components have led to a new generation of biohybrid devices based on microbial photocatalysts.These devices are limited by the poorly conductive interface between phototrophs and synthetic materials that inhibit charge transfer.This study focuses on overcoming this bottleneck through the metabolically-driven encapsulation of photosynthetic cells with a bio-inspired conductive polymer.Cells of the purple non sulfur bacterium Rhodobacter sphaeroides were coated with a polydopamine(PDA)nanoparticle layer via the self-polymerization of dopamine under anaerobic conditions.The treated cells show preserved light absorption of the photosynthetic pigments in the presence of dopamine concentrations ranging between 0.05-3.5 mM.The thickness and nanoparticle formation of the membrane-associated PDA matrix were further shown to vary with the dopamine concentrations in this range.Compared to uncoated cells,the encapsulated cells show up to a 20-fold enhancement in transient photocurrent measurements under mediatorless conditions.The biologically synthesized PDA can thus act as a matrix for electronically coupling the light-harvesting metabolisms of cells with conductive surfaces.
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