Gaseous therapy based on nitric oxide(NO),as a potential anti-tumor treatment strategy,has attracted great attention,but the targeted and controlled gas release in the tumor site still remains a challenge.In addressin...Gaseous therapy based on nitric oxide(NO),as a potential anti-tumor treatment strategy,has attracted great attention,but the targeted and controlled gas release in the tumor site still remains a challenge.In addressing these difficulties,a near-infrared(NIR)light-triggered NO release nanogenerator with a“linkage mechanism”was designed on the basis of sodium nitroprussidedoped mesoporous Prussian blue nanoparticles,in which the outer structure was modified with p H-sensitive gatekeeper chitosan and tumor-targeting agent folic acid.The“linkage mechanism”can achieve precise release of NO under the control of photothermal effect at tumor site,which can couple photothermal therapy and gas therapy to address the premature release of gas during transportation.Meanwhile,the amount of released gas can be controlled by adjusting the irradiation time and laser intensity.Furthermore,as-fabricated nanocomposites hold high photothermal conversion efficiency under NIR laser irradiation,resulting in the on-demand release of NO and chemotherapy drugs.The released NO can inhibit the expression of hypoxiainducible factorα(HIF-1α)and alleviate the hypoxic tumor microenvironment,thereby enhancing the efficacy of chemotherapy.Moreover,in vitro and in vivo experiments exhibited remarkable antitumor efficiency,and the synergistic gas/chemo/photothermal therapy of deep tumors was achieved.These findings indicate an effective strategy to stimulate further the development of deep tumor therapy,which may provide new insights into other NO-related medical applications.展开更多
Liver fibrosis, resulting from chronic liver damage and characterized by the accumulation of extracellular matrix (ECM) proteins, is a characteristic of most types of chronic liver diseases. The activation of hepatic ...Liver fibrosis, resulting from chronic liver damage and characterized by the accumulation of extracellular matrix (ECM) proteins, is a characteristic of most types of chronic liver diseases. The activation of hepatic stellate cells (HSC) is considered an essential pathological hallmark in liver fibrosis. Although nitric oxide (NO) can effectively induce HSC apoptosis, the systemic administration of NO is ineffective and may cause severe complications such as hypotension. To overcome this limitation, nanoparticles were designed to target HSCs and release NO locally under the exposure of near infrared light (NIR). To achieve this, upconversion nanoparticle (UCNP) cores were enveloped in mesoporous silica shells (UCNP@mSiO2), which were modified with hyaluronic acid (HA-UCNP@mSiO2) and Roussin’s black salt (RBS). HA molecules recognize and bind to CD44 proteins, which are overexpressed on activated HSCs. Under exposure to a 980-nm NIR laser, the UCNP cores convert the 980-nm wavelength into ultraviolet (UV) light, which then energizes the RBS (NO donors), resulting in an efficient release of NO inside of the HSCs. Once released, NO triggers HSC apoptosis and reverses the liver fibrosis. This targeted and controlled release method provides the theoretical and experimental basis for novel therapeutic approaches to treat hepatic fibrosis.展开更多
基金supported by the National Natural Science Foundation of China(21908059)the China Postdoctoral Science Foundation(2019M651419)+5 种基金the Shanghai Sailing Program(19YF1410900,21YF1451700)the Natural Science Foundation of Shanghai(22ZR1415400)the Fundamental Research Funds for the Central Universities(22221818014)the Shanghai Post-doctoral Excellence Program(2018011)the Foundation of State Key Laboratory of Biobased Material and Green Papermaking,Qilu University of Technology,Shandong Academy of Sciences(GZKF202031)the Open Funding Project of the State Key Laboratory of Bioreactor Engineering。
文摘Gaseous therapy based on nitric oxide(NO),as a potential anti-tumor treatment strategy,has attracted great attention,but the targeted and controlled gas release in the tumor site still remains a challenge.In addressing these difficulties,a near-infrared(NIR)light-triggered NO release nanogenerator with a“linkage mechanism”was designed on the basis of sodium nitroprussidedoped mesoporous Prussian blue nanoparticles,in which the outer structure was modified with p H-sensitive gatekeeper chitosan and tumor-targeting agent folic acid.The“linkage mechanism”can achieve precise release of NO under the control of photothermal effect at tumor site,which can couple photothermal therapy and gas therapy to address the premature release of gas during transportation.Meanwhile,the amount of released gas can be controlled by adjusting the irradiation time and laser intensity.Furthermore,as-fabricated nanocomposites hold high photothermal conversion efficiency under NIR laser irradiation,resulting in the on-demand release of NO and chemotherapy drugs.The released NO can inhibit the expression of hypoxiainducible factorα(HIF-1α)and alleviate the hypoxic tumor microenvironment,thereby enhancing the efficacy of chemotherapy.Moreover,in vitro and in vivo experiments exhibited remarkable antitumor efficiency,and the synergistic gas/chemo/photothermal therapy of deep tumors was achieved.These findings indicate an effective strategy to stimulate further the development of deep tumor therapy,which may provide new insights into other NO-related medical applications.
基金This work was supported by the American Heart Association(Nos.18TPA34230092 and 19EIA34660286 to K.C.)the National Natural Science Foundation of China(No.U1904149 to H.X.L.)+1 种基金National S&T Major Project of China(No.2018ZX10301201-008 to Z.G.R.)the High Technology Research and Development Program of Henan Province(No.20A320055 to H.X.L.).
文摘Liver fibrosis, resulting from chronic liver damage and characterized by the accumulation of extracellular matrix (ECM) proteins, is a characteristic of most types of chronic liver diseases. The activation of hepatic stellate cells (HSC) is considered an essential pathological hallmark in liver fibrosis. Although nitric oxide (NO) can effectively induce HSC apoptosis, the systemic administration of NO is ineffective and may cause severe complications such as hypotension. To overcome this limitation, nanoparticles were designed to target HSCs and release NO locally under the exposure of near infrared light (NIR). To achieve this, upconversion nanoparticle (UCNP) cores were enveloped in mesoporous silica shells (UCNP@mSiO2), which were modified with hyaluronic acid (HA-UCNP@mSiO2) and Roussin’s black salt (RBS). HA molecules recognize and bind to CD44 proteins, which are overexpressed on activated HSCs. Under exposure to a 980-nm NIR laser, the UCNP cores convert the 980-nm wavelength into ultraviolet (UV) light, which then energizes the RBS (NO donors), resulting in an efficient release of NO inside of the HSCs. Once released, NO triggers HSC apoptosis and reverses the liver fibrosis. This targeted and controlled release method provides the theoretical and experimental basis for novel therapeutic approaches to treat hepatic fibrosis.
