Enhancing metformin-induced tumor metabolism destruction by glucose oxidase for triple-combination therapy

Despite decades of laboratory and clinical trials,breast cancer remains the main cause of cancer-related disease burden in women.Considering the metabolism destruction effect of metformin(Met)and cancer cell starvation induced by glucose oxidase(GOx),after their efficient delivery to tumor sites,GOx and Met may consume a large amount of glucose and produce sufficient hydrogen peroxide in situ.Herein,a pH-responsive epigallocatechin gallate(EGCG)-conjugated low-molecular-weight chitosan(LC-EGCG,LE)nanoparticle(Met–GOx/Fe@LE NPs)was constructed.The coordination between iron ions(Fe3+)and EGCG in this nanoplatform can enhance the efficacy of chemodynamic therapy via the Fenton reaction.Met–GOx/Fe@LE NPs allow GOx to retain its enzymatic activity while simultaneously improving its stability.Moreover,this pH-responsive nanoplatform presents controllable drug release behavior.An in vivo biodistribution study showed that the intracranial accumulation of GOx delivered by this nanoplatform was 3.6-fold higher than that of the free drug.The in vivo anticancer results indicated that this metabolism destruction/starvation/chemodynamic triple-combination therapy could induce increased apoptosis/death of tumor cells and reduce their proliferation.This triple-combination therapy approach is promising for efficient and targeted cancer treatment.

Boosting ferroptosis and microtubule inhibition for antitumor therapy via a carrier-free supermolecule nanoreactor

Traditional microtubule inhibitors fail to significantly enhance+e effect of colorectal cancer;hence,new and efficient strategies are necessary.In+is study,a supramolecular nanoreactor(DOC@TA-Fe^(3+))based on tannic acid(TA),iron ion(Fe^(3+)),and docetaxel(DOC)wi+microtubule inhibition,reactive oxygen species(ROS)generation,and gluta+ione peroxidase 4(GPX4)inhibition,is prepared for ferroptosis/apoptosis treatment.After internalization by CT26 cells,+e DOC@TA-Fe^(3+)nanoreactor escapes from+e lysosomes to release payloads.+e subsequent Fe^(3+)/Fe^(2+)conversion mediated by TA reducibility can trigger+e Fenton reaction to enhance+e ROS concentration.Additionally,Fe^(3+)can consume gluta+ione to repress+e activity of GPX4 to induce ferroptosis.Meanwhile,+e released DOC controls microtubule dynamics to activate+e apoptosis pa+way.+e superior in vivo antitumor efficacy of DOC@TA-Fe^(3+)nanoreactor in terms of tumor grow+inhibition and improved survival is verified in CT26 tumor-bearing mouse model.+erefore,+e nanoreactor can act as an effective apoptosis and ferroptosis inducer for application in colorectal cancer+erapy.

Polydopamine-coated i-motif DNA/Gold nanoplatforms for synergistic photothermal-chemotherapy

The combination of photothermal therapywith chemotherapy has gradually developed into promising cancer therapy.Here,a synergistic photothermal-chemotherapy nanoplatform based on polydopamine(PDA)-coated gold nanoparticles(AuNPs)were facilely achieved via the in situ polymerization of dopamine(DA)on the surface of AuNPs.This nanoplatform exhibited augmented photothermal conversion efficiency and enhanced colloidal stability in comparison with uncoated PDA shell AuNPs.The i-motif DNA nanostructure was assembled on PDA-coated AuNPs,which could be transformed into a C-quadruplex structure under an acidic environment,showing a characteristic pH response.The PDA shell served as a linker between the AuNPs and the i-motif DNA nanostructure.To enhance the specific cellular uptake,the AS1411 aptamer was introduced to the DNA nanostructure employed as a targeting ligand.In addition,Dox-loaded NPs(DAu@PDA-AS141)showed the pH/photothermal-responsive release of Dox.The photothermal effect of DAu@PDA-AS141 elicited excellent photothermal performance and efficient cancer cell inhibition under 808 nm near-infrared(NIR)irradiation.Overall,these results demonstrate that the DAu@PDA-AS141 nanoplatform shows great potential in synergistic photothermal-chemotherapy.

Facile construction of targeted pH-responsive DNA-conjugated gold nanoparticles for synergistic photothermal-chemotherapy

Recently,stimuii-responsive DNA nano structure-based nanodevices have bee n applied for cancer therapy.In this study,pH-responsive i-motifDNA was modified on gold nanoparticles(AuNPs)via a facile,time-saving freeze-thaw method and utilized to construct stimuii-responsive drug nanocarriers.When the environment pH changes from 7.4 to 5.0,the i-motif DNA would be folded into four-stranded(C-quadruplex)that could be characterized by circular dichroism,and the characteristic of acid stimulate was verified by fluorescence resonanee energy transfer(FRET).To enhance specifical cellular uptake,MUC1 aptamer was employed as the targeting moiety.Doxorubicin(Dox)is an anticancer drug that can be efficiently intercalated into GC base pairs of DNA nanostructure to form drug-loaded nanovehicles(Dox@AuNP-MUCl).Additionally,owing to the excellent photothermal con version efficiency of AuNPs,the synergistic effect between chemotherapy and PTT can be readily achieved by 808 nm near-infrared(NIR)irradiation,which exhibits specifically and efficiently anticancer efficiency.Hence,this multifunctional drug carrier shows the potential for synergistic photothermal-chemotherapy.