Evoking robust immunogenic cell death by synergistic sonodynamic therapy and glucose depletion using Au clusters/single atoms modified TiO_(2)nanosheets

Facilitated by reactive oxygen species(ROS)-involved therapies,tumor cells undergo immunogenic cell death(ICD)to stimulate long-term immunity response.However,it is hard to trigger abundant and large-scale ICD for satisfactory cancer immunotherapy.Herein,a multifunctional sonosensitizer that consists of Au single atoms and clusters anchored on TiO_(2)nanosheets(named Au_(S/C)-TiO_(2))is reported for augmented sonodynamic therapy(SDT)and glucose depletion,which ultimately induce robust ICD due to the improved ROS generation and strong endoplasmic reticulum(ER)stress.The synergy effect between Au cluster/single atom with TiO_(2)nanosheets intensifies apoptosis and ICD pathways to inhibit 80%of tumor cells through in vivo analyses.Furthermore,immune cells in vivo analyses verify the effectiveness of Au_(S/C)-TiO_(2)sonosensitizer towards the induction of antitumor immunity.This study thus reveals that simultaneous presence of ROS generation and strong ER stress can efficiently evoke a strong ICD-mediated immune response.

Platelet membrane-coated C-TiO_(2) hollow nanospheres for combined sonodynamic and alkyl-radical cancer therapy

The therapeutic efficiency of sonodynamic therapy(SDT)mainly depends on the presence of oxygen(O_(2))to generate harmful reactive oxygen species(ROS);thus,the hypoxic tumor microenvironment significantly limits the efficacy of SDT.Therefore,the development of oxygen-independent free radical generators and associated combination therapy tactics can be a promising field to facilitate the anticancer capability of SDT.In this study,a biomimetic drug delivery system(C-TiO_(2)/AIPH@PM)composed of an alkyl-radical generator(2,2′-azobis[2-(2-imidazolin-2-yl)propane]dihydrochloride,AIPH)-loaded C-TiO_(2) hollow nanoshells(HNSs)as the inner cores,and a platelet membrane(PM)as the outer shells is successfully prepared for synergistic SDT and oxygen-independent alkyl-radical therapy.The PM encapsulation can significantly prolong the blood circulation time of CTiO_(2)/AIPH@PM compared with C-TiO_(2)/AIPH while enabling C-TiO_(2)/AIPH@PM to achieve tumor targeting.C-TiO_(2)/AIPH@PM can efficiently produce ROS and alkyl radicals,which can achieve a more thorough tumor eradication regardless of the normoxic or hypoxic conditions.Furthermore,the generation of these radicals improves the efficiency of SDT.In addition,nitrogen(N_(2))produced due to the decomposition of AIPH enhances the acoustic cavitation effect and lowers the cavitation threshold,thereby enhancing the penetration of CTiO_(2)/AIPH@PM at the tumor sites.Both in vitro and in vivo experiments demonstrate that CTiO_(2)/AIPH@PM possesses good biosafety,ultrasound imaging performance,and excellent anticancer efficacy.This study provides a new strategy to achieve oxygen-independent free radical production and enhance therapeutic efficacy by combining SDT and free radical therapy.

Upconversion nanoparticles@AgBiS_(2) core-shell nanoparticles with cancer-cell-specific cytotoxicity for combined photothermal and photodynamic therapy of cancers

UCNPs@AgBiS_(2) core-shell nanoparticles that AgBiS_(2) coated on the surface of upconversion nanoparticles (UCNPs) was successfully prepared through an ion exchange reaction. The photothermal conversion efficiency of AgBiS_(2) can be improved from 14.7% to 45% due to the cross relaxation between Nd ions and AgBiS_(2). The doping concentration of Nd ions played a critical role in the production of reactive oxygen species (ROS) and enhanced the photothermal conversion efficiency. The NaYF4:Yb/Er/Nd@NaYF4:Nd nanoparticles endows strong upcon-version emissions when the doped concentration of Nd ions is 1% in the inner core, which excites the AgBiS_(2) shell to produce ROS for photodynamic therapy (PDT) of cancer cells. As a result, the as-prepared NaYF4:Yb/Er/ Nd@NaYF4:Nd@AgBiS_(2) core-shell nanoparticles showed combined photothermal/photodynamic therapy (PTT/ PDT) against malignant tumors. This work provides an alternative near-infrared light-active multimodal nano-structures for applications such as fighting against cancers.

Anti-inflammatory catecholic chitosan hydrogel for rapid surgical trauma healing and subsequent prevention of tumor recurrence

Although occupying pillar position in clinical cancer treatments,surgery itself and surgical trauma would elicit series of local/systemic inflammation-related responses that resulted in high rate of tumor recurrence.Herein,chitosan with conjugated gallic acid(CSG)molecules were coordinated with Fe3+to form CSG/Fe3+hydrogel for filling the tumo r-resected cavity with considerable wet-adhesion ability and anti-inflammatory performance.With the assistance of doxorubicin hydrochloride(DOX·HCl),CSG/Fe3+/DOX hydrogel exhibited syne rgistic photothermal-chemo tumo r-inhibited performance under near-infrared(NIR)light irradiation for eradicating residual and/or surgical trauma-recruited cancer cells.Thus,our study attempts to show a paradigm that realizes quick surgical trauma healing,inflammation inhibition and prevention of postsurgical tumor recurrence.

Antibacterial mechanism and transcriptomic analysis of a nearinfrared triggered upconversion nanoparticles@AgBiS2 for synergetic bacteria-infected therapy

Methicillin-resistant Staphylococcus aureus(MRSA)has become a rising clinical problem as its occurrence has increased due to the overuse and misuse of antibiotics.In this work,upconversion nanoparticles@AgBiS2 core–shell were produced with enhanced photothermal transformation efficiency and ability to produce reactive oxygen species for synergistic photodynamic photothermal and photodynamic antibacterial performance.The nanoparticles exhibit good antibacterial effects in vitro and satisfactory therapeutic performance on healing MRSA-infected wounds in vivo experiments.RNA-sequencing technique has been used to investigate and reveal that photothermal–photodynamic therapy using the nanoparticles can interfere with metabolic processes such as galactose metabolism in MRSA bacteria,destroy the transport system on the surface of MRSA,and affect quorum sensing to hinder the formation of biofilms to achieve effective antibacterial efficacy.It was demonstrated that this work presents an alternative near-infrared photoactive multimodal nanostructure for antibacterial applications.

Biomimetic copper single-atom nanozyme system for self-enhanced nanocatalytic tumor therapy

Single-atom nanozymes(SAZs)with peroxidase(POD)-like activity have good nanocatalytic tumor therapy(NCT)capabilities.However,insufficient hydrogen peroxide(H2O2)and hydrogen ions in the cells limit their therapeutic effects.Herein,to overcome these limitations,a biomimetic single-atom nanozyme system was developed for self-enhanced NCT.We used a previously described approach to produce platelet membrane vesicles.Using a high-temperature carbonization approach,copper SAZs with excellent POD-like activity were successfully synthesized.Finally,through physical extrusion,a proton pump inhibitor(PPI;pantoprazole sodium)and the SAZs were combined with platelet membrane vesicles to create PPS.Both in vivo and in vitro,PPS displayed good tumor-targeting and accumulation abilities.PPIs were able to simultaneously regulate the hydrogen ion,glutathione(GSH),and H2O2 content in tumor cells,significantly improve the catalytic ability of SAZs,and achieve self-enhanced NCT.Our in vivo studies showed that PPS had a tumor suppression rate of>90%.PPS also limited the synthesis of GSH in cells at the source;thus,glutamine metabolism therapy and NCT were integrated into an innovative method,which provides a novel strategy for multimodal tumor therapy.