Tumor Microenvironment-Adaptive Nanoplatform Synergistically Enhances Cascaded Chemodynamic Therapy

Chemodynamic therapy(CDT),a noninvasive strategy,has emerged as a promising alternative to conventional chemotherapy for treating tumors.However,its therapeutic effect is limited by the amount of H_(2)O_(2),pH value,the hypoxic environment of tumors,and it has suboptimal tumor-targeting ability.In this study,tumor cell membrane-camouflaged mesoporous Fe_(3)O_(4) nanoparticles loaded with perfluoropentane(PFP)and glucose oxidase(GOx)are used as a tumor microenvironment-adaptive nanoplatform(M-mFeP@O_(2)-G),which synergistically enhances the antitumor effect of CDT.Mesoporous Fe_(3)O_(4) nanoparticles are selected as inducers for photothermal and Fenton reactions and as nanocarriers.GOx depletes glucose within tumor cells for starving the cells,while producing H2O2 for subsequent⋅OH generation.Moreover,PFP,which can carry O_(2),relieves hypoxia in tumor cells and provides O_(2) for the cascade reaction.Finally,the nanoparticles are camouflaged with osteosarcoma cell membranes,endowing the nanoparticles with homologous targeting and immune escape abilities.Both in vivo and in vitro evaluations reveal high synergistic therapeutic efficacy of M-mFeP@O_(2)-G,with a desirable tumor-inhibition rate(90.50%),which indicates the great potential of this platform for clinical treating cancer.

Cancer-specific calcium nanoregulator suppressing the generation and circulation of circulating tumor cell clusters for enhanced anti-metastasis combinational chemotherapy

Tumor metastasis is responsible for chemotherapeutic failure and cancer-related death.Moreover,circulating tumor cell(CTC)clusters play a pivotal role in tumor metastasis.Herein,we develop cancer-specific calcium nanoregulators to suppress the generation and circulation of CTC clusters by cancer membrane-coated digoxin(DIG)and doxorubicin(DOX)co-encapsulated PLGA nanoparticles(CPDDs).CPDDs could precisely target the homologous primary tumor cells and CTC clusters in blood and lymphatic circulation.Intriguingly,CPDDs induce the accumulation of intracellular Ca^(2+) by inhibiting Na^(+)/K^(+)-ATPase,which help restrain cellecell junctions to disaggregate CTC clusters.Meanwhile,CPDDs suppress the epithelialemesenchymal transition(EMT)process,resulting in inhibiting tumor cells escape from the primary site.Moreover,the combination of DOX and DIG at a mass ratio of 5:1 synergistically induces the apoptosis of tumor cells.In vitro and in vivo results demonstrate that CPDDs not only effectively inhibit the generation and circulation of CTC clusters,but also precisely target and eliminate primary tumors.Our findings present a novel approach for anti-metastasis combinational chemotherapy.