CaCO_(3)-MnSiO_(x)hybrid particles to enable CO_(2)-mediated combinational tumor therapy

Nanocatalysts mediated reactive oxygen species(ROS)based therapy has been exploited as an alternative therapeutic modality of tumor with high specificity and minimal side effects.However,the treatment outcome is limited by the efficiency of local catalytic reaction.Herein,we report a novel type of core–shell hybrid nanoparticles(CaCO_(3)@MS),consisting of CaCO_(3)and MnSiO_(x),for synergistic tumor inhibition combining enhanced catalytic effect and calcium overload.In this system,MnSiO_(x)serves as catalysts with glutathione(GSH)responsive Mn^(2+)ions release functionality.CaCO_(3)nanoparticles play three important roles,including carbon dioxide(CO_(2))donor,pH modulator,and Ca^(2+)overload agent.It is found that the CaCO_(3)nanoparticles can induce CO_(2)production and pH increase in acidic tumor environment,both of which promote Mn^(2+)mediated ROS generation.And simultaneous release of Ca^(2+)ions from CaCO_(3)triggers calcium overload in tumor,which functions collaboratively with excessive ROS to induce cancer cell apoptosis.The results demonstrate that after treatment with CaCO_(3)@MS,a remarkable tumor inhibition was achieved both in vitro and in vivo,while no clear toxic effect was observed.This study has therefore provided a feasible effective approach to improve catalytic therapeutic efficacy by an“exogenous CO_(2)delivery”strategy for combinational tumor therapy.

ATP-responsive hollow nanocapsules for DOX/GOx delivery to enable tumor inhibition with suppressed P-glycoprotein

Multidrug resistance(MDR)restricts chemotherapy efficacy due to P-glycoprotein(P-gp)mediated drug efflux,whereas current approaches to suppressing P-gp expression suffer from intrinsic challenges,such as low transfection,high toxicity and poor specificity.Here,hollow ferric-tannic acid complex nanocapsules(HFe-TA),which can be effectively degraded by the reaction with adenosine triphosphate(ATP),are synthesized for the delivery of glucose oxidase(GOx)and doxorubicin(DOX)for tumor treatment.The findings indicate that the intracellular ATP is significantly decreased due to the combined effect of HFe-TA degradation and GOx-mediated glucose consumption.Along with this ATP down-regulation,P-gp expression of tumor cells is suppressed remarkably,which in turn promotes the intracellular accumulation and anticancer efficacy of DOX.In addition,the production of•OH by Fe ions released from HFe-TA is promoted by the by-products of the oxidation of glucose process by GOx.In consequence,HFe-TA nanocapsules loaded with DOX and GOx enable significant inhibition effect to tumors both in vitro and in vivo due to the synergistic effect of cascade reactions.This study has therefore provided an alternative therapeutic platform for effective tumor inhibition with the potential in overcoming intrinsic MDR.