Bio-inspired nanoenzyme for metabolic reprogramming and antiinflammatory treatment of hyperuricemia and gout

Gout,a common type of inflammatory arthritis resulting from chronic elevation of uric acid(UA)level,is usually accompanied with hyperuricemia.The current clinical drugs for the treatment of gout and hyperuricemia are greatly restricted by their limited therapeutic efficacy,off-target toxicity and severe side effects.Here,a neutrophil membrane(NM)-coated and cascade catalytic nanoenzyme was devised with excellent inflammation targeting,inflammatory cytokines neutralizing and UA degrading characteristics for the treatment of gout and hyperuricemia with high efficacy and safety.This nanoenzyme was fabricated by encapsulating uricase(UOx)and catalase(CAT)into zeolitic imidazolate framework-8(ZIF-8)and further coating it with NM.The NM-coated nanoenzyme inherits the antigenic exterior and cell membrane functions of neutrophils for inflammation targeting and cytokine neutralization.UOx and CAT encapsulated in ZIF-8 could efficiently degrade UA and eliminate hydrogen peroxide(H_(2)O_(2))via a biocatalytic cascade,thus successfully blocking the inflammation amplification during gout development.Both in vitro and in vivo experiments demonstrated the preferable potentials of the nanoenzyme for gout targeting,inflammation elimination and UA degradation,exhibiting great promise for the treatment of gout and hyperuricemia in an effective and safe manner.

Tumor Cell Membrane-Coated Liquid Metal Nanovaccine for Tumor Prevention

Herein,we report on a tumor nanovaccine LMNP@CM that enhances the process of antigen-presenting by stimulating the immune system to uptake tumor antigens actively.The nanovaccine is comprised of polyethylene glycol modified liquid metal nanoparticles(LMNP)and tumor cell membra nes(CM)as antigens.Under 808 nm irradiation,the photothermal con version effect of injected LMNP can cause mild local inflammation,and subsequently induces antigen-presenting cells active recruitment and facilitates cellular uptake of tumor antigens.Meanwhile,because of the immune adjuvant effect of metal materials,the nanovaccine LMNP@CM promotes the maturation and activation of antigen-presenting cells and induces anti-tumor immune response effectively.By priming the host immune recognition of tumor antigens,this nanovaccine displays prophylactic effects and significantly suppresses tumor growth in a mouse breast tumor model.The nanovaccine LMNP@CM represents a novel strategy of utilizing light-controlled means to actively induce anti-tumor immune processes,showing advanced therapeutic potentials and robust adaptability for treating multiple tumors by changing the loaded antigens.

A Singlet Oxygen Reservoir Based on Poly-Pyridone and Porphyrin Nanoscale Metal-Organic Framework for Cancer Therapy

Here,a methacrylate-modified pyridone derivative(mPYR)was loaded into a porphyrin nanoscale metal-organic framework(porphyrin-nMOF).Then,the loaded mPYR was further polymerized to obtain poly-pyridone(poly-mPYR)to form poly-mPYR loaded porphyrin-nMOF,which is designated as PLP and used as a reservoir of singlet oxygen(^(1)O_(2)).It was found that PLP could quickly capture^(1)O_(2)in vitro and slowly release^(1)O_(2)in vivo to induce cancer cell death.The release of^(1)O_(2)was light and oxygen independent,and the entire process did not cause intracellular oxygen consumption.PLP also displayed good therapeutic effect in the treatment of both solid tumor and lung metastasis cancer.This strategy of oxygenand light-independent^(1)O_(2)treatment presents great potential for treating refractory cancer.Also,the form of^(1)O_(2)capturing polymer-loaded nMOF expands the biomedical applications of MOFs and polymers,which can be used as a platform for biomedical applications.

Antibacterial Sutures Coated with Smooth Chitosan Layer by Gradient Deposition

Owing to the significant importance in clinics,antibacterial activity is thought as one indispensable feature of the next generation of absorbable sutures.It is challenging but imperative to arm the existing absorbable sutures with antibacterial functions.The present study describes a“gradient deposition”technique to coat a continuous and smooth layer of chitosan on the surface of absorbable sutures.Specifically,chitosan solution is arranged to undergo gradient pH decline step by step while during each pH interval,the solution is allowed to stand for a predetermined period of time in order to control gradual chitosan deposition.Chitosan nanoparticles are found to be first generated on suture surface and finally developed into a smooth chitosan layer as the antibacterial surface.In vitro and in vivo results demonstrated that coating chitosan on sutures by our technique could relieve wound inflammation,stimulate collagen deposition,regenerate blood vessels,and assist tissue repairing,consequently leading to a significant enhancement of wound healing effect.This technique is highlighted with low cost,extreme convenience and excellent safety without organic solvents.Furthermore,the“gradient deposition”technique would not affect the fundamental properties of matrix and thus hold promises as a universal way for superficial antibacterial modification towards almost all the surgical implanted materials,including but not limited to absorbable sutures.