Spatially asymmetric cascade nanocatalysts for enhanced chemodynamic therapy

Chemodynamic therapy(CDT)based on cascade catalytic nanomedicine has emerged as a promising cancer treatment strategy.However,most of the reported cascade catalytic systems are designed based on symmetric-or co-assembly of multiple catalytic active sites,in which their functions are difficult to perform independently and may interfere with each other.Especially in cascade catalytic system that involves fragile natural-enzymes,the strong oxidation of free-radicals toward natural-enzymes should be carefully considered,and the spatial distribution of the multiple catalytic active sites should be carefully organized to avoid the degradation of the enzyme catalytic activity.Herein,a spatially-asymmetric cascade nanocatalyst is developed for enhanced CDT,which is composed by a Fe_(3)O_(4)head and a closely connected mesoporous silica nanorod immobilized with glucose oxidase(mSiO_(2)-GOx).The mSiO_(2)-GOx subunit could effectively deplete glucose in tumor cells,and meanwhile produce a considerable amount of H_(2)O_(2)for subsequent Fenton reaction under the catalysis of Fe_(3)O_(4)subunit in the tumor microenvironment.Taking the advantage of the spatial isolation of mSiO_(2)-GOx and Fe_(3)O_(4)subunits,the catalysis of GOx and freeradicals generation occur at different domains of the asymmetric nanocomposite,minimizing the strong oxidation of free-radicals toward the activity of GOx at the other side.In addition,direct exposure of Fe_(3)O_(4)subunit without any shelter could further enhance the strong oxidation of free-radicals toward objectives.So,compared with traditional core@shell structure,the long-term stability and efficiency of the asymmetric cascade catalytic for CDT is greatly increased by 138%,thus realizing improved cancer cell killing and tumor restrain efficiency.

External physical field-driven nanocatalytic cancer therapy

Recently,variable nanocatalysts have provided novel,highly selective,mini-mally invasive strategies driven by external physical fields for cancer therapy.In the catalytic reaction,less toxic or nontoxic substances can be in situ converted into toxic agents for cancer suppression.In this review,we systematically summarize the catalytic cancer therapy based on different types of external physical fields,including light,ultrasound,electricity,temperature,X-ray,magnetic field,and microwave.The properties,mechanisms,and advantages of the corresponding external physical fields in cancer therapy are also intro-duced.Importantly,considering the rapid development of catalytic nano-medicine,the research progress of catalytic cancer therapy driven by external physical fields is discussed.Finally,the remaining challenges and outlooks that catalytic cancer therapy faced are also outlined.We believe that the emerging external physical fields-driven nanocatalytic cancer therapy will provide a new avenue for cancer treatment.

Cerium oxide nanoparticles-mediated cascade catalytic chemo-photo tumor combination therapy

ROS-based tumor therapy based on nanocatalytic medicine has recently been proposed for its tumor-specificity.However,a safe and highly efficient strategy towards getting high enough ROS to kill the hypoxic cancer cells is still a great challenge.Herein,we report a simple pH/H_()20_(2)-activatable,O_(2)-evolving,and ROS regulating doxorubicin(DOX)and indocyanine green(ICG)co-loading PEGylated polyaniline(PANI)coated CeOx@polyacrylic acid(PAA)nanoclusters for highly selective and optimized cancer combination treatment.It can selectively and greatly enhance intracellular O_(2) and ROS levels in tumor region,which depends on two-step catalytic properties of nanoceria(Ce^(4+)/Ce^(3+)=3.46,neutral surface charge,mostly localize into the cytoplasm,pH 7.4-6.5,catalase-like catalytic agents convert to Ce^(4+)/Ce^(3+)=0.58,negative surface charge,mostly localize into the lysosomes,pH 5-4,oxidase-like catalytic agents,triggered by near infrared(NIA)laser irradiation).Furthermore,the protective effect of polyethylene glycol(PEG),PANI,and PAA ensure that the nanoceria can only play the role of catalase under the irradiation of NIR light arrived at the tumor area.Moreover,loading of nanoceria and ICG onto PANI greatly enhanced photo thermal effect of nanoparticles.(NPs),which is useful for killing cancer cells by relieving hypoxia and promoting cross-membrane drug delivery.to further enhance photodynamic therapy and chemotherapy efficiency.The chemo-photo combination therapies fantastically inhibited tumor growth and prevented tumor recurrence in vivo,suggesting a smart nanotheranostic system to achieve more precise and effective therapies in O_(2)-deprived tumor tissue.