CD151-enriched migrasomes mediate hepatocellular carcinoma invasion by conditioning cancer cells and promoting angiogenesis.

BACKGROUND: The tetraspanin family plays a pivotal role in the genesis of migrasomes, and Tetraspanin CD151 is also implicated in neovascularization within tumorous contexts. Nevertheless, research pertaining to the involvement of CD151 in hepatocellular carcinoma (HCC) neovascularization and its association with migrasomes remains inadequate. METHODS: To investigate the correlation between CD151 and migrasome marker TSPAN4 in liver cancer, we conducted database analysis using clinical data from HCC patients. Expression levels of CD151 were assessed in HCC tissues and correlated with patient survival outcomes. In vitro experiments were performed using HCC cell lines to evaluate the impact of CD151 expression on migrasome formation and cellular invasiveness. Cell lines with altered CD151 expression levels were utilized to study migrasome generation and in vitro invasion capabilities. Additionally, migrasome function was explored through cellular aggregation assays and phagocytosis studies. Subsequent VEGF level analysis and tissue chip experiments further confirmed the role of CD151 in mediating migrasome involvement in angiogenesis and cellular signal transduction. RESULTS: Our study revealed a significant correlation between CD151 expression and migrasome marker TSPAN4 in liver cancer, based on database analysis of clinical samples. High expression levels of CD151 were closely associated with poor survival outcomes in HCC patients. Experimentally, decreased CD151 expression led to reduced migrasome generation and diminished in vitro invasion capabilities, resulting in attenuated in vivo metastatic potential. Migrasomes were demonstrated to facilitate cellular aggregation and phagocytosis, thereby promoting cellular invasiveness. Furthermore, VEGF-enriched migrasomes were implicated in signaling and angiogenesis, accelerating HCC progression. CONCLUSIONS: In summary, our findings support the notion that elevated CD151 expression promotes migrasome formation, and migrasomes play a pivotal role in the invasiveness and angiogenesis of liver cancer cells, thereby facilitating HCC progression. This finding implies that migrasomes generated by elevated CD151 expression may constitute a promising high-priority target for anti-angiogenic therapy in HCC, offering crucial insights for the in-depth exploration of migrasome function and a renewed comprehension of the mechanism underlying liver cancer metastasis.

Protective function of sclerosing cholangitis on IBD.

OBJECTIVE: There is a strong clinical association between IBD and primary sclerosing cholangitis (PSC), a chronic disease of the liver characterised by biliary inflammation that leads to strictures and fibrosis. Approximately 60%-80% of people with PSC will also develop IBD (PSC-IBD). One hypothesis explaining this association would be that PSC drives IBD. Therefore, our aim was to test this hypothesis and to decipher the underlying mechanism. DESIGN: Colitis severity was analysed in experimental mouse models of colitis and sclerosing cholangitis, and people with IBD and PSC-IBD. Foxp3+ Treg-cell infiltration was assessed by qPCR and flow cytometry. Microbiota profiling was carried out from faecal samples of people with IBD, PSC-IBD and mouse models recapitulating these diseases. Faecal microbiota samples collected from people with IBD and PSC-IBD were transplanted into germ-free mice followed by colitis induction. RESULTS: We show that sclerosing cholangitis attenuated IBD in mouse models. Mechanistically, sclerosing cholangitis causes an altered intestinal microbiota composition, which promotes Foxp3+ Treg-cell expansion, and thereby protects against IBD. Accordingly, sclerosing cholangitis promotes IBD in the absence of Foxp3+ Treg cells. Furthermore, people with PSC-IBD have an increased Foxp3+ expression in the colon and an overall milder IBD severity. Finally, by transplanting faecal microbiota into gnotobiotic mice, we showed that the intestinal microbiota of people with PSC protects against colitis. CONCLUSION: This study shows that PSC attenuates IBD and provides a comprehensive insight into the mechanisms involved in this effect.

Low field controllable continuous spin switching in the thulium-ytterbium single crystal.

We report the spin reorientation transition (SRT) and the low field controllable continuous spin switching (SSW) of the Tm0.75Yb0.25FeO3 (TYFO) single crystal in this study. The SRT, characterized by the transition from Γ2(Fx, Cy, Gz)-Γ4(Gx, Ay, Fz), occurs within the temperature range of 20-27 K. Under an external magnetic field of 50 Oe, the SSW occurs along the c-axis at approximately 98 K due to the reversal of Tm3+ magnetic moment induced by the magnetic coupling change between Tm3+ and Fe3+, transitioning from a parallel to an antiparallel alignment. Notably, a continuous SSW is observed along the a-axis at low temperatures, which has not been previously reported in rare earth orthoferrites. This unique behavior can be easily manipulated by low magnetic fields within the temperature range of 2-20 K. Both the spin reorientation transition and spin switching phenomena in the TYFO single crystal arise from interactions between rare earth ions and iron ions and can be effectively regulated by applied low magnetic fields, making it a promising material for low-field spin devices.

In Situ-Derived N-Doped ZnO from ZIF-8 for Enhanced Ethanol Sensing in ZnO/MEMS Devices.

Microelectromechanical systems (MEMS) gas sensors have numerous advantages such as compact size, low power consumption, ease of integration, etc., while encountering challenges in sensitivity and high resistance because of their low sintering temperature. This work utilizes the in situ growth of Zeolitic Imidazolate Framework-8 (ZIF-8) followed by its conversion to N-doped ZnO. The results obtained from scanning electron microscopy (SEM) and transmission electron microscopy (TEM) indicate that the in situ derivation of ZIF-8 facilitates the adhesion of ZnO particles, forming an island-like structure and significantly reducing the interfaces between these particles. Furthermore, powder X-ray diffraction (XRD) analysis, elemental mapping, and X-ray photoelectron spectroscopy (XPS) analysis confirm the conversion of ZIF-8 to ZnO, the successful incorporation of N atoms into the ZnO lattice, and the creation of more oxygen vacancies. The ZIF-8-derived N-doped ZnO/MEMS sensor (ZIF (3)-ZnO/MEMS) exhibits remarkable gas sensitivity for ethanol detection. At an operating temperature of 290 °C, it delivers a substantial response value of 80 towards 25 ppm ethanol, a 13-fold enhancement compared with pristine ZnO/MEMS sensors. The sensor also exhibits an ultra-low theoretical detection limit of 11.5 ppb to ethanol, showcasing its excellent selectivity. The enhanced performance is attributed to the incorporation of N-doped ZnO, which generates abundant oxygen vacancies on the sensor's surface, leading to enhanced interaction with ethanol molecules. Additionally, a substantial two-order-of-magnitude decrease in the resistance of the gas-sensitive film is observed. Overall, this study provides valuable insights into the design and fabrication strategies applicable to high-performance MEMS gas sensors in a broader range of gas sensing.

SnO2/Au Microelectromechanical Systems Modified by Oxygen Vacancies for Enhanced Sensing of Dioctyl Phthalate.

Dioctyl phthalate (DOP) serves as a characteristic gas utilized in early electrical fire detection, its detection offers promising prospects for the prevention of electrical fires. In this study, we employed a modified photodeposition method to prepare Tin dioxide (SnO2) materials co-modified with Au and oxygen vacancies. Subsequently, microelectromechanical systems (MEMS) gas sensor for DOP detection were fabricated, utilizing 0.5 %Au/SnO2-I as the sensing material. Characterization results reveal the presence of abundant oxygen vacancies in 0.5 %Au/SnO2-I. The synergistic interplay of Au and oxygen vacancies resulted in a remarkable response of 9.98 to 20 ppm of DOP at operational temperature of 250 °C. This represents a significant 96 % enhancement in comparison to the response value of 4.50 exhibited by pure SnO2 at 300 °C. Notably, this gas sensor boasts low power consumption and demonstrates a quick response in the detection of overheating polyvinyl chloride (PVC) cables under simulated conditions.

Photochemical engineering unsaturated Pt islands on supported Pd nanocrystals for a robust pH-universal hydrogen evolution reaction.

The rational design of heterostructured nanocrystals (HNCs) is of great significance for developing highly efficient hydrogen evolution reaction (HER) electrocatalysts. However, a significant challenge still lies in realizing the controllable synthesis of desired HNCs directly onto a support and exploring their structure-activity-dependent HER performance. Herein, we reported various controllable Pd7@Ptx core-shell HNCs with optimal hybrid structures via a photochemical deposition strategy. The growth patterns of a Pt shell can be finely controlled by adjusting the growth kinetics, resulting in a varying deposition rate. In particular, the as-prepared Pd7@Pt3 HNCs with a Pt shell in the Stranski-Krastanov mode showed the best performances over a wide pH range media, delivering low overpotentials of 33, 18 and 49 mV, resulting in a catalytic current density of 10 mA cm-2 at a low effective catalyst loading of 0.021 mg cm-2. The resulting Tafel slopes were 23.1, 52.6 and 42.7 mV dec-1 in 0.5 M H2SO4, 1.0 M phosphate-buffered saline (PBS) and 1.0 M KOH electrolyte, respectively. It was found that the increased fraction of unsaturated coordination of Pt islands in the resultant material is the key to the enhanced and robust HER activity, which has been confirmed through density functional theory (DFT) calculations. This strategy could be extended to the rational design and synthesis of other heterostructured catalysts for energy conversion and storage.

Fabrication of heterogeneous bimetallic nanochains through photochemical welding for promoting the electrocatalytic hydrogen evolution reaction.

Heterogeneous bimetallic nanochains (NCs) have gained significant attention in the field of catalysis due to their abundant active sites, multi-component synergistic catalytic, and exotic electronic structures. Here, we present a novel approach to synthesize one-dimensional heterogeneous bimetallic nanochains using a local surface plasmon resonance (LSPR) based strategy of liquid-phase photochemical welding method containing self-assembly and subsequent welding processes. Initially, we introduce additives that facilitate the self-assembly and alignment of Au nanoparticles (NPs) into orderly lines. Subsequently, the LSPR effect of the Au NPs is stimulated by light, enabling the second metal precursor to overcome the energy barrier and undergo photodeposition in the gap between the arranged Au NPs, thereby connecting the nano-metal particles. This strategy can be extended to the photochemical welding of Au NPs-Ag and Au NRs. Using electrocatalytic hydrogen evolution reaction (HER) as a proof-of-concept application, the obtained one-dimensional structure of Au5Pt1 NCs exhibit promoted HER performances, where the mass activity of the Au5Pt1 nanochains is found to be 4.8 times higher than that of Au5Pt1 NPs and 10.4 times higher than that of commercial 20 wt% Pt/C catalysts. The promoted HER performance is benefited from the electron conduction ability and abundant active sites.

A 3D Cross-Linked Metal-Organic Framework (MOF)-Derived Polymer Electrolyte for Dendrite-Free Solid-State Lithium-Ion Batteries.

Lithium metal batteries (LMBs) with high energy density have received widespread attention; however, there are usually issues with lithium dendrite growth and safety. Therefore, there is a demand for solid electrolytes with high mechanical strength, room-temperature ionic conductivity, and good interface performance. Herein, a 3D cross-linked metal-organic framework (MOF)-derived polymer solid electrolyte exhibits good mechanical and ionic conductive properties simultaneously, in which the MOF with optimized pore size and strong imidazole cation sites can restrict the migration of anions, resulting in a uniform Li+ flux and a high lithium-ion transference number (0.54). Moreover, the MOF-derived polymer solid electrolytes with the 3D cross-linked network can promote the rapid movement of Li+ and inhibit the growth of lithium dendrites. Lithium symmetric batteries assembled with the 3D MOF-derived polymer solid electrolytes are subjected to lithium plating/stripping and cycled over 2000 h at a current density of 0.1 mA cm-2 and over 800 h at a current density of 0.2 mA cm-2 . The Li/P-PETEA-MOF/LiFePO4 batteries exhibit excellent long-cycle stability and cycle reversibility.

CD4+ T cell-derived IL-22 enhances liver metastasis by promoting angiogenesis.

Metastasis is a cancer-related systemic disease and is responsible for the greatest mortality rate among cancer patients. Interestingly, the interaction between the immune system and cancer cells seems to play a key role in metastasis formation in the target organ. However, this complex network is only partially understood. We previously found that IL-22 produced by tissue resident iNKT17 cells promotes cancer cell extravasation, the early step of metastasis. Based on these data, we aimed here to decipher the role of IL-22 in the last step of metastasis formation. We found that IL-22 levels were increased in established metastatic sites in both human and mouse. We also found that Th22 cells were the key source of IL-22 in established metastasis sites, and that deletion of IL-22 in CD4+ T cells was protective in liver metastasis formation. Accordingly, the administration of a murine IL-22 neutralizing antibody in the establishment of metastasis formation significantly reduced the metastatic burden in a mouse model. Mechanistically, IL-22-producing Th22 cells promoted angiogenesis in established metastasis sites. In conclusion, our findings highlight that IL-22 is equally as important in contributing to metastasis formation at late metastatic stages, and thus, identify it as a novel therapeutic target in established metastasis.

A Surfactant-Free and General Strategy for the Synthesis of Bimetallic Core-Shell Nanocrystals on Reduced Graphene Oxide through Targeted Photodeposition.

Tunable physicochemical properties of bimetallic core-shell heterostructured nanocrystals (HNCs) have shown enormous potential in electrocatalytic reactions. In many cases, HNCs are required to load on supports to inhibit catalyst aggregation. However, the introduction of supports during the process of growing core-shell HNCs makes the synthesis much more complicated and difficult to control precisely. Herein, we reported a universal photochemical synthetic strategy for the controlled synthesis of well-defined surfactant-free core-shell metal HNCs on a reduced graphene oxide (rGO) support, which was assisted by the fine control of photogenerated electrons directly transferring to the targeted metal seeds via rGO and the precisely tuned adsorption capacity of the added second metal precursors. The surface photovoltage microscopy (SPVM) platform proved that photogenerated electrons flowed through rGO to Pd particles under illumination. We have successfully synthesized 24 different core-shell metal HNCs, i.,e., MA@MB (MA = Pd, Au, and Pt; MB = Au, Ag, Pt, Pd, Ir, Ru, Rh, Ni and Cu), on the rGO supports. The as-prepared Pd@Cu core-shell HNCs showed outstanding performance in the electrocatalytic reduction of CO2 to CH4. This work could shed light on the controlled synthesis of more functional bimetallic nanostructured materials on diverse supports for various applications.

A comprehensive review of the relationship between autophagy and sorafenib-resistance in hepatocellular carcinoma: ferroptosis is noteworthy.

Patients with hepatocellular carcinoma (HCC) bear a heavy burden of disease and economic burden but have fewer treatment options. Sorafenib, a multi-kinase inhibitor, is the only approved drug that can be used to limit the progression of inoperable or distant metastatic HCC. However, enhanced autophagy and other molecular mechanisms after sorafenib exposure further induce drug resistance in HCC patients. Sorafenib-associated autophagy also generates a series of biomarkers, which may represent that autophagy is a critical section of sorafenib-resistance in HCC. Furthermore, many classic signaling pathways have been found to be involved in sorafenib-associated autophagy, including the HIF/mTOR signaling pathway, endoplasmic reticulum stress, and sphingolipid signaling, among others. In turn, autophagy also provokes autophagic activity in components of the tumor microenvironment, including tumor cells and stem cells, further impacting sorafenib-resistance in HCC through a special autophagic cell death process called ferroptosis. In this review, we summarized the latest research progress and molecular mechanisms of sorafenib-resistance-associated autophagy in detail, providing new insights and ideas for unraveling the dilemma of sorafenib-resistance in HCC.

Highly Selective Catalytic Oxi-upcycling of Polyethylene to Aliphatic Dicarboxylic Acid under a Mild Hydrogen-Free Process.

A low-temperature hydrogen-free process for upcycling polyethylene (PE) plastics into aliphatic dicarboxylic acid is developed using a heterogeneous catalyst Ru/TiO2 . The low-density PE (LDPE) conversion can reach 95 % in 24 h under a pressure of 1.5 MPa air at 160 °C with 85 % of the liquid product yield, which mainly is low molecular weight aliphatic dicarboxylic acid. Excellent performances can be also achieved for different PE feedstocks. This catalytic oxi-upcycling process paving a new way of upcycling polyethylene waste.

Quantitative Structure-Electrochemistry Relationship (QSER) Studies on Metal-Amino-Porphyrins for the Rational Design of CO2 Reduction Catalysts.

The quantitative structure-electrochemistry relationship (QSER) method was applied to a series of transition-metal-coordinated porphyrins to relate their structural properties to their electrochemical CO2 reduction activity. Since the reactions mainly occur within the core of the metalloporphyrin catalysts, the cluster model was used to calculate their structural and electronic properties using density functional theory with the M06L exchange-correlation functional. Three dependent variables were employed in this work: the Gibbs free energies of H*, C*OOH, and O*CHO. QSER, with the genetic algorithm combined with multiple linear regression (GA-MLR), was used to manipulate the mathematical models of all three Gibbs free energies. The obtained statistical values resulted in a good predictive ability (R2 value) greater than 0.945. Based on our QSER models, both the electronic properties (charges of the metal and porphyrin) and the structural properties (bond lengths between the metal center and the nitrogen atoms of the porphyrin) play a significant role in the three Gibbs free energies. This finding was further applied to estimate the CO2 reduction activities of the metal-monoamino-porphyrins, which will prove beneficial in further experimental developments.

Antagonizing EZH2 combined with vitamin D3 exerts a synergistic role in anti-fibrosis through bidirectional effects on hepatocytes and hepatic stellate cells.

BACKGROUND AND AIM: Whether vitamin D3 (VD3) supplementation is associated with improved liver fibrosis is controversial. METHODS: Liver fibrosis models were treated with VD3, active VD (1,25-OH2 Vitamin D3), or collaboration with GSK126 (Ezh2 inhibitor), respectively. Hepatic stellate cells (HSCs) were co-cultured with hepatocytes and then stimulated with TGF-ß. Autophagy of hepatocytes was determined after the intervention of 1,25-OH2 Vitamin D3 and GSK126. Also, the active status of HSCs and the mechanism with 1,25-OH2 Vitamin D3 and GSK126 intervention were detected. RESULTS: 1,25-OH2 Vitamin D3, but not VD3, is involved in anti-fibrosis and partially improves liver function, which might be associated with related enzymes and receptors (especially CYP2R1), leading to decreased of its biotransformation. GSK126 plays a synergistic role in anti-fibrosis. The co-culture system showed increased hepatocyte autophagy after HSCs activation. Supplementation with 1,25-OH2 Vitamin D3 or combined GSK126 reduced these effects. Further studies showed that 1,25-OH2 Vitamin D3 promoted H3K27 methylation of DKK1 promoter through VDR/Ezh2 due to the weakening for HSCs inhibitory signal. CONCLUSIONS: VD3 bioactive form 1,25-OH2 Vitamin D3 is responsible for the anti-fibrosis, which might have bidirectional effects on HSCs by regulating histone modification. The inhibitor of Ezh2 plays a synergistic role in this process.

Protocol on irradiation-dark photochemical deposition and characterization of metal nanoclusters on semiconductor support.

Controlling the size and uniform dispersion of noble metal nanoclusters on the metal oxide based semiconductor are difficult due to the natural tendency for metal atoms to agglomerate. Here, we present the protocol for an "irradiation-dark" photochemical deposition to obtain uniform metal nanoclusters on semiconductor support, and the protocol for measuring the size and size distribution of metal nanoclusters. For complete details on the use and execution of this protocol, please refer to Wu et al. (2022).

Shape-Controlled Photochemical Synthesis of Noble Metal Nanocrystals Based on Reduced Graphene Oxide.

The fabrication of supported noble metal nanocrystals (NCs) with well-controlled morphologies have been attracted considerable interests due to their merits in a wide variety of applications. Photodeposition is a facile and effective method to load metals over semiconductors in a simple slurry reactor under irradiation. By optimizing the photodeposition process, the size, chemical states, and the geometrical distribution of metal NCs have been successfully tuned. However, metal NCs with well-controlled shapes through the photodeposition process have not been reported until now. Here, we report our important advances in the controlled photodeposition process to load regular noble metal NCs. Reduced graphene oxide (rGO) is introduced as a reservoir for the fast transfer of photoelectrons to avoid the fast accumulation of photogenerated electrons on the noble metals which makes the growth process uncontrollable. Meanwhile, rGO also provides stable surface for the controlled nucleation and oriented growth. Noble metal NCs with regular morphologies are then evenly deposited on rGO. This strategy has been demonstrated feasible for different precious metals (Pd, Au, and Pt) and semiconductors (TiO2, ZnO, ZrO2, CeO2, and g-C3N4). In the prototype application of electrochemical hydrogen evolution reaction, regular Pd NCs with enclosed {111} facets showed much better performance compared with that of irregular Pd NCs.

Localized surface plasmon resonance induced assembly of bimetal nanochains.

Bimetal nanochains (NCs) are attracting increasing attention in the fields of catalysis and electrocatalysis due to the synergistic effects in electronic and optical properties, but the fabrication of bimetal NCs remains challenging. Here, we report a general strategy named "nucleation in the irradiation then growth in the dark" for the preparation of Au/M (second metal) NCs. In the irradiation stage, the localized surface plasmon resonance (LSPR) effect of Au NPs is excited to overcome the nucleation energy barrier for the deposition of second metals (Pt, Ag and Pd). In the followed dark process, the preferential growth of second metals on the existed nucleus leads to the formation of nanochain rather than the core/shell nanostructure. In the model reaction of electrocatalytic hydrogen evolution, the optimized Au/Pt NCs showed much better performance compared with the commercial Pt/C.

Shielding Ferritin with a Biomineralized Shell Enables Efficient Modulation of Tumor Microenvironment and Targeted Delivery of Diverse Therapeutic Agents.

Ferritin (Fn) is considered a promising carrier for targeted delivery to tumors, but the successful application in vivo has not been fully achieved yet. Herein, strong evidence is provided that the Fn receptor is expressed in liver tissues, resulting in an intercept effect in regards to tumor delivery. Building on these observations, a biomineralization technology is rationally designed to shield Fn using a calcium phosphate (CaP) shell, which can improve the delivery performance by reducing Fn interception in the liver while re-exposing it in acidic tumors. Moreover, the selective dissolution of the CaP shell not only neutralizes the acidic microenvironment but also induces the intratumoral immunomodulation and calcification. Upon multiple cell line and patient-derived xenografts, it is demonstrated that the elaboration of the highly flexible Fn@CaP chassis by loading a chemotherapeutic drug into the Fn cavity confers potent antitumor effects, and additionally encapsulating a photosensitizer into the outer shell enables a combined chemo-photothermal therapy for complete suppression of advanced tumors. Altogether, these results support Fn@CaP as a new nanoplatform for efficient modulation of the tumor microenvironment and targeted delivery of diverse therapeutic agents.

MOFs-based nanoagent enables dual mitochondrial damage in synergistic antitumor therapy via oxidative stress and calcium overload.

Targeting subcellular organelle with multilevel damage has shown great promise for antitumor therapy. Here, we report a core-shell type of nanoagent with iron (III) carboxylate metal-organic frameworks (MOFs) as shell while upconversion nanoparticles (UCNPs) as core, which enables near-infrared (NIR) light-triggered synergistically reinforced oxidative stress and calcium overload to mitochondria. The folate decoration on MOFs shells enables efficient cellular uptake of nanoagents. Based on the upconversion ability of UCNPs, NIR light mediates Fe3+-to-Fe2+ reduction and simultaneously activates the photoacid generator (pHP) encapsulated in MOFs cavities, which enables release of free Fe2+ and acidification of intracellular microenvironment, respectively. The overexpressed H2O2 in mitochondria, highly reactive Fe2+ and acidic milieu synergistically reinforce Fenton reactions for producing lethal hydroxyl radicals (•OH) while plasma photoacidification inducing calcium influx, leading to mitochondria calcium overload. The dual-mitochondria-damage-based therapeutic potency of the nanoagent has been unequivocally confirmed in cell- and patient-derived tumor xenograft models in vivo.

Macrophage-tumor chimeric exosomes accumulate in lymph node and tumor to activate the immune response and the tumor microenvironment.

Despite multiple immunotherapeutic technologies that achieve potent T cell activation, effector T cells still lack efficiency because of the highly immunosuppressive conditions in the tumor microenvironment. Inspired by recent advances in nano-sized secreted vesicles known as exosomes as therapeutic agents and research revealing that circulating cancer cells have a "homing" capacity to return to the main tumor sites, we generated macrophage-tumor hybrid cells. We introduced nuclei isolated from tumor cells into activated M1-like macrophages to produce chimeric exosomes (aMT-exos). The aMT-exos were able to accumulate in both lymph nodes and diverse tumors of xenograft mice. They entered lymph nodes and primed T cell activation in both the classical antigen-presenting cell­induced immunostimulatory manner and a unique "direct exosome interaction" manner. aMT-exos also had strong "homing behavior" to tumor sites, where they ameliorated immunosuppression. They were effective in inducing tumor regression and extending survival in primary mouse models of lymphoma and breast and melanoma cancers. In addition, when combined with anti­programmed death 1 (a-PD1) treatment, aMT-exos were able to extend survival of metastatic and postsurgical tumor recurrence mouse models. Such a coactivation of the immune response and the tumor microenvironment enabled aMT-exos to confer efficient inhibition of primary tumors, tumor metastases, and postoperative tumor recurrence for personalized immunotherapy, which warrants further exploration in the clinical setting.