Tumor-responsive copper-activated disulfiram for synergetic nanocatalytic tumor therapy

Exploring alternative biomedical use of traditional drugs in different disease models is highly important as it can reduce the cost of drug development and overcome several critical issues of traditional chemodrugs such as low chemotherapeutic efficiency,severe side effect,and drug resistance.Disulfiram(DSF),a clinically approved alcohol-aversion drug,was recently demonstrated tofeature tumor-growth suppression effect along with the co-administration of Cu^(2+)species,but direct Cu^(2+)administration mode might cause severe toxicity originating from low Cu^(2+)accumulation into the tumor and nonspecific Cu^(2+)distribution-induced cytotoxicity.Based on the intriguing drug-delivery performance of nanoscale metal-organic frameworks(MOFs),we herein construct HKUST nMOFs as the Cu^(2+)self-supplying nanocarriers for efficient delivery of the D SF drug.The mildly acidic condition of tumor microenvironment initially triggered the release of Cu ions from HKUST nMOFs,which further reacted with the encapsulated DSF toform toxic Cu(DDTC)2(activation)for tumor chemotherapy.Especially,during the Cu(DDTC)2 complexation,Cu^(+)species were formed concomitantly,triggering the intratumoral nanocatalytic therapy for the generation of reactive oxygen species to synergistically destroying the tumor cells/tissue.As a result,synergetic tumor-responsive chemotherapy and nanocatalytic therapy are enabled by DSF@HKU ST nanodrugs,as demonstrated by the dominant anticancer efficacy with satisfied biocompatibility both in vitro and in vivo.The present work offers a sophisticated strategy for tumor-responsive nontoxic-to-toxic therapeutic with high biocompatibility.

Nanocatalytic Medicine of Iron-Based Nanocatalysts

Iron can be found in all mammalian cells and is of critical significance to diverse cellular activities within human bodies.Widespread applications and the underlying chemical and biological fundamental explorations of iron-based nanomaterials,especially on the biomedical frontiers,have attracted growing interests most recently in the community.In this review,we focus on the catalytic performance of iron-based nanomaterials(termed as nanocatalysts,abbreviated as NCs)and their nanocatalytic biomedical applications in Fenton nanocatalytic therapeutics,nanocatalytic oxygenation-enabled therapeutics,and nanocatalytic peroxidation-enabled biodetections.Fabrication methodologies of the iron-based NCs are also summarized along with their applications.Representative therapeutic performance against malignant tumors,Alzheimer’s disease(and other pathological abnormalities),and nanocatalyticbased biodetection are discussed.Finally,future development prospects of the iron-based NCs are surveyed,aiming to deliver a brighter future for iron-based NCs in nanocatalytic medicine.