The Novel PH-responsive Metalcontaining Nanoplatform For Tumor Safety Therapy

Cancer,also denoted as malignant tumor,mainly results from the aberrant changes of genes and uncommitted growths of abnormal cells.Due to the complicated operation mechanism of tumor cells,cancer has become the dominating cause of death worldwide.Thus,the diagnosis and treatment of canser obtain the extensive attention in life science and clinical research.Over the past few decades,although significative progress in cancer therapy has been made,there are still remain severe challenge for satisfactory therapy efficiency in many cases.In this regard,various ingenious nanoplatform,serving as the novel approaches of tumor treatment,has been widely explored.In particular,the activatable biocompatible nanosystem responded to internal or external stimulation,such as pH and light,has been utilized for intelligent tumor ablation.In this article,we constructured three novel pH-responsive metal-based nanoplatform for on-demand cancer safety therapy.The main content of the article is divided as below:1.The reasonable administration of chemotherapy and hydroxyl radical(·OH)-mediated chemodynamic therapy(CDT)keeps great potential for cancer therapy.Herein,a simple approach was employed to prepare biocompatible porous core-shell Cu₂O nanocrystals(Cu₂O-PEG NCs),which were used to catalyze hydrogen peroxide(H₂O₂)into toxic·OH via the Fenton-like reaction and simultaneously load doxorubicin(DOX)for chemo/chemodynamic synergistic therapy.Interestingly,the in-situ formed high-density hydrophilic PEG outside Cu₂O significantly improved the stability and compatibility of NCs.The porosity of Cu₂O-PEG NCs endowed the capacity of efficient DOX loading(DOX@Cu₂O-PEG NCs)and delivery.Particularly,the obtained DOX@Cu₂O-PEG NCs acted as the excellent nanocatalyst,which could release Fenton-like Cu⁺by an acid-triggered manner to catalyze the generation of·OH for reactive oxygen species(ROS)-involved CDT.The rapidly released DOX due to pH-induced decomposition of Cu₂O-PEG NCs simultaneously obtained chemotherapy and elevated the amount of H₂O₂ for enhanced CDT.After intravenous injection,Cu₂O-PEG NCs effectively accumulated in tumor region improved by external high density of PEG shell.In vitro and in vivo experiments demonstrated the admirable treatment capacity and high biocompatibility.2.Based on the last work,we further reported an activatable autocatalytic nanoreactor(HT@GOx-DMONs)for self-boosted Fenton-like CDT via ingeniously decorating Cu²⁺-based metal-organic frameworks(MOFs)on glucose oxidase(GOx)-loaded dendritic mesoporous organosilica nanoparticles(DMONs).The as-prepared nanoreactor could prevent the premature leakage of Cu²⁺and GOx in neutral physiological conditions conducted by the growing carboxylate MOFs(HKUST-1),but the fast release of agents could be observed in acidic environment of endo/lysosomes,which thereby endowed the nanoreactor with the performance of pH-activated·OH generation driven by Cu⁺-mediated autocatalytic Fenton-like reaction.Excitingly,Cu²⁺-induced glutathione(GSH)depletion and GOx-catalyzed H₂O₂ self-sufficiency unlocked by acidity dramatically magnified·OH generation.As expected,the self-enhanced·OH-mediated CDT exhibited wonderful in vitro toxicity and in vivo antitumor ability via ROS-involved oxidative damage without causing the significant systemic toxicity.3.In the previous works,we realized the efficive suppression of tumor growth by constructing smart nanoplatform,but the active targeting of nanoagents could not be achieved.Thus,Fe³⁺-based MOFs were in-site decorated on polyvinylpyrrolidone(PVP)-stable polydopamine nanoparticles(PDANPs),which then encapsulated GOx via hyaluronic acid(HA)coating to structure an intelligent CD44-targeted core-shell nanoedicine(HG-MIL@PDANPs)for tumor-specific photothermal-chemodynamic synergistic therapy.The resulting nanomedicine with inner core of PDANPs displayed prominent near-infrared(NIR)-induced photothermal performance,which could effectively ablate tumor via high heat.Excitingly,the pH-triggered and NIR-enhanced degradation of outer shell could obtain the rapid release of Fe³⁺and GOx.Additionally,Fe³⁺-involved GSH depletion and GOx-catalyzed acidity recovery and H₂O₂ self-sufficiency could exactly boosted·OH generation for CDT via improving Fe²⁺-driven Fenton reaction.Unexpectedly,the introduction of HA ligand could not only accelerate the cellular uptake of nanomedicine for CD44-overexpressed tumor cells,but also prolong the circulating half-life time of nanomedicine in bloodstream.As a result,the obtained nanomedicine presented an admirable accumulation in tumor region.Except for the efficient growth inhibition of tumor cells,HG-MIL@PDANPs showed satisfactory in vivo tumor ablation without evident side-effects by the site-specific synergy of controllable PTT and enhanced CDT.