Sorafenib sensitization in tumor therapy by iron overload and AMPK activation

Sorafenib,as a first-line drug for advanced hepatocellular carcinoma(HCC),could trigger ferroptosis by inhibiting cystine/glutamate transporter.However,low-level intracellular iron and insufficient activation of adenosine monophosphate(AMP)-activated protein kinase(AMPK)confer impaired response to sorafenib.In this study,a unique sorafenib nanocomposite dexterously modified with Fe-Material of Institut Lavoisier(sora@Fe-MIL)was synthesized to escalate intracellular iron level and activate AMPK,further potentiating the ferroptotic effect of sorafenib.Remarkably,this strategic deployment of sora@Fe-MIL triggered an extensive demise of cancer cells,while manifesting negligible deleterious impact on normal cells.Two prominent ferroptosis biomarkers,glutathione peroxidase 4(GPX4)and solute carrier family 7 member 11(SLC7A11),underwent pronounced downregulation,underscoring the efficacy of this strategy in inducing ferroptosis.Furthermore,the bioactivity of AMPK was considerably elevated,and its downstream targets were conspicuously inhibited by the treatment with sora@Fe-MIL.Using orthotopic HCC animal models,we observed a substantial suppression of primary in situ tumor growth,and ribonucleic acid(RNA)sequencing elucidated an elevated degree of ferroptosis and AMPK activation with the treatment of sora@Fe-MIL.In conclusion,we proposed that the meticulously designed strategy for secure and efficacious iron release and AMPK activation could significantly potentiate the ferroptotic impact of sorafenib,thus resuscitating its therapeutic response in HCC patients.

Reductive damage induced autophagy inhibition for tumor therapy

Numerous therapeutic anti-tumor strategies have been developed in recent decades.However,their therapeutic efficacy is reduced by the intrinsic protective autophagy of tumors.Autophagy plays a key role in tumorigenesis and tumor treatment,in which the overproduction of reactive oxygen species(ROS)is recognized as the direct cause of protective autophagy.Only a few molecules have been employed as autophagy inhibitors in tumor therapy to reduce protective autophagy.Among them,hydroxychloroquine is the most commonly used autophagy inhibitor in clinics,but it is severely limited by its high therapeutic dose,significant toxicity,poor reversal efficacy,and nonspecific action.Herein,we demonstrate a reductive-damage strategy to enable tumor therapy by the inhibition of protective autophagy via the catalytic scavenging of ROS using porous nanorods of ceria(PN-CeO_(2))nanozymes as autophagy inhibitor.The antineoplastic effects of PN-CeO_(2)were mediated by its high reductive activity for intratumoral ROS degradation,thereby inhibiting protective autophagy and activating apoptosis by suppressing the activities of phosphatidylinositide 3-kinase/protein kinase B and p38 mitogen-activated protein kinase pathways in human cutaneous squamous cell carcinoma.Further investigation highlighted PN-CeO_(2)as a safe and efficient anti-tumor autophagy inhibitor.Overall,this study presents a reductive-damage strategy as a promising anti-tumor approach that catalytically inhibits autophagy and activates the intrinsic antioxidant pathways of tumor cells and also shows its potential for the therapy of other autophagy-related diseases.

Phytic acid-modified CeO_(2) as Ca^(2+) inhibitor for a security reversal of tumor drug resistance

Ca^(2+)plays critical roles in the development of diseases,whereas existing various Ca regulation methods have been greatly restricted in their clinical applications due to their high toxicity and inefficiency.To solve this issue,with the help of Ca overexpressed tumor drug resistance model,the phytic acid(PA)-modified CeO_(2) nano-inhibitors have been rationally designed as an unprecedentedly safe and efficient Ca2+inhibitor to successfully reverse tumor drug resistance through Ca^(2+)negative regulation strategy.Using doxorubicin(Dox)as a model chemotherapeutic drug,the Ca^(2+)nano-inhibitors efficiently deprived intracellular excessive free Ca2+,suppressed P-glycoprotein(P-gp)expression and significantly enhanced intracellular drug accumulation in Dox-resistant tumor cells.This Ca^(2+)negative regulation strategy improved the intratumoral Dox concentration by a factor of 12.4 and nearly eradicated tumors without obvious adverse effects.Besides,nanocerias as pH-regulated nanozyme greatly alleviated the adverse effects of chemotherapeutic drug on normal cells/organs and substantially improved survivals of mice.We anticipate that this safe and effective Ca^(2+)negative regulation strategy has potentials to conquer the pitfalls of traditional Ca inhibitors,improve therapeutic efficacy of common chemotherapeutic drugs and serves as a facile and effective treatment platform of other Ca^(2+) associated diseases.

Unconventional energy： Seeking the ways to innovate energy science and technology

With the energy and environmental problems becoming increasingly serious, pursuing ideal energy or its utilization ways has never been so urgent as it was. So far, tremendous efforts in the research of energy science and technologies have been conducted.

Enhanced photothermal conversion and thermal conductivity of phase change n-octadecane microcapsules shelled with nano-SiC doped crosslinked polystyrene

Microcapsules incorporating phase change material n-octadecane(ODE)shelled with crosslinked polystyrene(CLPS)were prepared via the suspension polymerization.SiC nanoparticles(nano-SiC)were employed to modify the shell to improve the heat transfer and photothermal conversion of the microcapsules.The scanning electron microscopic analysis revealed the microcapsules of a general spherical shape.The surface components and chemical composition of the microcapsule samples were evaluated by the energy-dispersive X-ray and Fourier transform infrared spectroscopy,confirming that the nano-SiC have been embedded in the CLPS shell.Results show that the microcapsule sample with 1.25 wt.%nano-SiC(denoted as MPCM3)exhibits the best heat property among the four kinds of samples prepared with various nano-SiC dosages,and all the nano-SiC doped samples have improved thermal conductivity and photothermal conversion as compared to the microcapsule sample without doping(denoted as MPCM1).Compared to the MPCM1,the thermal conductivity of the MPCM3 is increased by 65.3%,reaching 0.124±0.005 W·m^(−1)·K^(−1).The MPCM3 has excellent thermal stability as well.Differential scan-ning calorimetry examination shows that the MPCM3 has higher melting and crystallization enthalpies than the MPCM1,achieving 106.8±0.3 J·g^(−1) and 104.9±0.2 J·g^(−1),respectively.In the photothermal conversion experi-ments,the MPCM3 exhibited great photothermal conversion capability,with a 54.91%photothermal conversion efficiency,which is 145.68%higher than that of the MPCM1.