Bimetallic nanoparticles as cascade sensitizing amplifiers for low-dose and robust cancer radio-immunotherapy

Radiotherapy(RT)is one of the most feasible and routinely used therapeutic modalities for treating malignant tumors.In particular,immune responses triggered by RT,known as radio-immunotherapy,can partially inhibit the growth of distantly spreading tumors and recurrent tumors.How-ever,the safety and efficacy of radio-immunotherapy is impeded by the radio-resistance and poor immu-nogenicity of tumor.Herein,we report oxaliplatin(IV)-iron bimetallic nanoparticles(OXA/Fe NPs)as cascade sensitizing amplifiers for low-dose and robust radio-immunotherapy.The OXA/Fe NPs exhibit tumor-specific accumulation and activation of OXA(I)and Fe^(2+)in response to the reductive and acidic microenvironment within tumor cells.The cascade reactions of the released metallic drugs can sensitize RT by inducing DNA damage,increasing ROS and O_(2) levels,and amplifying the immunogenic cell death(ICD)effect after RT to facilitate potent immune activation.As a result,OXA/Fe NPs-based low-dose RT triggered a robust immune response and inhibited the distant and metastatic tumors effectively by a strong abscopal effect.Moreover,a long-term immunological memory effect to protect mice from tumor rechal-lenging is observed.Overall,the bimetallic NPs-based cascade sensitizing amplifier system offers an effi-cient radio-immunotherapy regimen that addresses the key challenges.

Optical control of neuronal activities with photoswitchable nanovesicles

Precise modulation of neuronal activity by neuroactive molecules is essential for understanding brain circuits and behavior.However,tools for highly controllable molecular release are lacking.Here,we developed a photoswitchable nanovesicle with azobenzene-containing phosphatidylcholine(azo-PC),coined‘azosome’,for neuromodulation.Irradiation with 365 nm light triggers the trans-to-cis isomerization of azo-PC,resulting in a disordered lipid bilayer with decreased thickness and cargo release.Irradiation with 455 nm light induces reverse isomerization and switches the release off.Real-time fluorescence imaging shows controllable and repeatable cargo release within seconds(<3 s).Importantly,we demonstrate that SKF-81297,a dopamine D1-receptor agonist,can be repeatedly released from the azosome to activate cultures of primary striatal neurons.Azosome shows promise for precise optical control over the molecular release and can be a valuable tool for molecular neuroscience studies.

The associated killing of hepatoma cells using multilayer drug-loaded mats combined with fast neutron therapy

Chemotherapeutic and radiation therapy have emerged as two most important treatment strategies to treat cancer in clinical practice;however,to improve anticancer efficacy,combination chemotherapy still remains challenge.Dichloroacetate(DCA)could produce significant cytotoxic effects in certain tumor cells through its distinct mechanism.Radiation therapy with fast neutrons(FNT)has high relative biolgical effectiveness compared to other radiotherapeutics.Herein,we reported the combination chemotherapy with FNT for effective tumor growth inhibition with the assistance of a multilayered nanofiber loading DCA and DCA derivatives.We first synthesized a biodegradable polylysine to condense DCA with negative charge,or to conjugate DCA by condensing synthesis,to obtain Ion-DCA and Co-DCA,respectively.DCA,Ion-DCA or Co-DCA was then loaded into fibers to form multilayer drug-loaded mats.Upon adhesion on the surface of subcutaneous and orthotopic liver tumors,the multilayer drug-loaded mats realized a controllable release of DCA,which reversed the Warburg effect and inhibited cancer cell proliferation.Meantime,irradiation of fast neutrons could seriously damage DNA structure.Combination of the controllable release of DCA and FNT resulted in synergistic cell apoptosis in vitro,and the tumor inhibition in vivo.This study thus provides a new approach to integrate chemotherapy and FNT with the assistance of biocompatible nanofiber for synergistic tumor therapy.