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Local recurrence is a common cause of treatment failure for patients with solid tumors. Tumor-specific intraoperative fluorescence imaging may improve staging and debulking efforts in cytoreductive surgery and, thereby improve prognosis. Here, we report in vivo assembly of the second near-infrared window (NIR-II) emitting downconversion nanoparticles (DCNPs) modified with DNA and targeting peptides to improve the image-guided surgery for metastatic ovarian cancer. The NIR-II imaging quality with DCNPs is superior to that of clinically approved ICG with good photostability and deep tissue penetration (8 mm). Stable tumor retention period experienced 6 h by in vivo assembly of nanoprobes can be used for precise tumor resection. Superior tumor-to-normal tissue ratio is successfully achieved to facilitate the abdominal ovarian metastases surgical delineation. Metastases with ≤1 mm can be completely excised under NIR-II bioimaging guidance. This novel technology provides a general new basis for the future design of nanomaterials for medical applications. Real-time fluorescence imaging in the NIR-II region offers non-invasive detection of ovarian metastatic tumors and their image-guided surgery. Here the authors describe NIR-II nanoprobes in vivo assembly for detection of disseminated ovarian cancer.

(+)-JQ1 is an inhibitor of the tumor-driver bromodomain protein BRD4 and produces satisfactory effects because it efficiently increases apoptosis. Ferroptosis is an oxidative cell death program differing from apoptosis. Ferroptosis is characterized by high levels of iron and reactive oxygen species and has been confirmed to suppress tumor growth. In this study, BRD4 expression in cancer and its influence on the prognosis of cancer patients were analyzed using data from public databases. In addition, the effect of the BRD4 inhibitor (+)-JQ1 on ferroptosis was investigated via a series of in vitro assays. A nude mouse model was used to evaluate the function of (+)-JQ1 in ferroptosis in vivo. The potential mechanisms by which (+)-JQ1 regulates ferroptosis were explored. The results showed that BRD4 expression levels were higher in cancer tissues than in normal tissues and were related to poor prognosis in cancer patients. Furthermore, ferroptosis was induced under (+)-JQ1 treatment and BRD4 knockdown, indicating that (+)-JQ1 induces ferroptosis via BRD4 inhibition. Moreover, the anticancer effect of (+)-JQ1 was enhanced by ferroptosis inducers. Further studies confirmed that (+)-JQ1 induced ferroptosis via ferritinophagy, which featured autophagy enhancement by (+)-JQ1 and increased iron levels. Subsequently, the reactive oxygen species levels were increased by iron via the Fenton reaction, leading to ferroptosis. In addition, expression of the ferroptosis-associated genes GPX4 , SLC7A11 , and SLC3A2 was downregulated under (+)-JQ1 treatment and BRD4 knockdown, indicating that (+)-JQ1 may regulate ferroptosis by controlling the expression of ferroptosis-associated genes regulated by BRD4. Finally, (+)-JQ1 regulated ferritinophagy and the expression of ferroptosis-associated genes via epigenetic inhibition of BRD4 by suppressing the expression of the histone methyltransferase G9a or enhancing the expression of the histone deacetylase SIRT1. In summary, the BRD4 inhibitor (+)-JQ1 induces ferroptosis via ferritinophagy or the regulation of ferroptosis-associated genes through epigenetic repression of BRD4.

Satellite laser ranging allows to measure distances to satellites equipped with retroreflectors in orbits up to 36000 km. Utilizing a higher powered laser, space debris laser ranging detects diffuse reflections from defunct satellites or rocket bodies up to a distance of 3000 km. So far space debris laser ranging was only possible within a few hours around twilight while it is dark at the satellite laser ranging station and space debris is illuminated by the sun. Here we present space debris laser ranging results during daylight. Space debris objects are visualized against the blue sky background and biases corrected in real-time. The results are a starting point for all space debris laser ranging stations to drastically increase their output in the near future. A network of a few stations worldwide will be able to improve orbital predictions significantly as necessary for removal missions, conjunction warnings, avoidance maneuvers or attitude determination. Space debris laser ranging is a technique to measure distances to defunct satellites or rocket bodies in orbits around Earth which was only possible within a few hours around twilight. Here, the authors show the first space debris laser ranging results during daylight while correcting inaccurate predictions using a real-time target detection software.

Satellite laser ranging and space debris laser ranging are two closely related range measurement techniques with slightly different setups relying on different lasers. Satellite laser ranging measures light reflections of corner cube retro reflectors at mm-level range precision. Space debris laser ranging gathers diffuse reflections from the whole space debris object and offers a precision down to the sub meter-level. Within this work we show the usage of Megahertz lasers to combine the strengths of both systems within one setup. During the regular tracking schedule to scientific satellite laser ranging targets, specific space debris objects of interest can then be tracked without the need of making adaptions to the system. Megahertz satellite laser ranging measurements to the defunct Jason-2 satellite lead to a measurement precision down to a few μ m when ranging to retro reflectors. Space debris laser ranging data reveals reflections from individual surfaces of the target and allows to draw conclusions on the rotational behavior. Space debris laser ranging, and satellite laser ranging are currently performed with slightly different setups. Here, the authors show a single setup with a Megahertz laser for both high-precision satellite laser ranging and space debris laser ranging.

Hepatocellular carcinoma (HCC) commonly emerges in an immunologically “cold” state, thereafter protects it away from cytolytic attack by tumor‐infiltrating lymphocytes, resulting in poor response to immunotherapy. Herein, an acidic/photo‐sensitive dendritic cell (DCs)‐based neoantigen nano‐vaccine has been explored to convert tumor immune “cold” state into “hot”, and remodel tumor‐associated neutrophils to potentiate anticancer immune response for enhancing immunotherapy efficiency. The nano‐vaccine is constructed by SiPCCl2‐hybridized mesoporous silica with coordination of Fe(III)‐captopril, and coating with exfoliated membrane of matured DCs by H22‐specific neoantigen stimulation. The nano‐vaccines actively target H22 tumors and induce immunological cell death to boost tumor‐associated antigen release by the generation of excess 1O2 through photodynamic therapy, which act as in situ tumor vaccination to strengthen antitumor T‐cell response against primary H22 tumor growth. Interestingly, the nano‐vaccines are also home to lymph nodes to directly induce the activation and proliferation of neoantigen‐specific T cells to suppress the primary/distal tumor growth. Moreover, the acidic‐triggered captopril release in tumor microenvironment can polarize the protumoral N2 phenotype neutrophils to antitumor N1 phenotype for improving the immune effects to achieve complete tumor regression (83%) in H22‐bearing mice and prolong the survival time. This work provides an alternative approach for developing novel HCC immunotherapy strategies. Acidic/photo‐sensitive dendritic cell‐based neoantigen nano‐vaccine is developed to convert tumor immune “cold” into “hot”, and remodel tumor‐associated neutrophils for enhancing HCC immunotherapy. The nano‐vaccines actively targeted tumors to boost tumor‐associated antigen release, and home to lymph nodes to directly activate neoantigen‐specific T cells. The acidic‐triggered captopril release reduced the protumoral N2 neutrophils for synergetic suppression of the primary/distal tumor growth.

Despite the importance of nanoparticle’s multipods topology in multivalent-interactions enhanced nano-bio interactions, the precise manipulation of multipods surface topological structures is still a great challenge. Herein, the surface-kinetics mediated multi-site nucleation strategy is demonstrated for the fabrication of mesoporous multipods with precisely tunable surface topological structures. Tribulus-like tetra-pods Fe 3 O 4 @SiO 2 @RF&PMOs (RF = resorcinol-formaldehyde resin, PMO = periodic mesoporous organosilica) nanocomposites have successfully been fabricated with a centering core@shell Fe 3 O 4 @SiO 2 @RF nanoparticle, and four surrounding PMO nanocubes as pods. By manipulating the number of nucleation sites through mediating surface kinetics, a series of multipods mesoporous nanocomposites with precisely controllable surface topological structures are formed, including Janus with only one pod, nearly plane distributed dual-pods and tri-pods, three-dimensional tetrahedral structured tetra-pods, etc. The multipods topology endows the mesoporous nanocomposites enhanced bacteria adhesion ability. Particularly, the tribulus-like tetra-pods mesoporous nanoparticles show ~100% bacteria segregation and long-term inhibition over 90% after antibiotic loading. Control of composite nanoparticle topology can be difficult. Here the authors control the topological structure of mesoporous multipods by controlling the number of nucleation sites, and they used the resultant nanoparticles for bacterial adhesion, segregation and antibiotic delivery.

Background The biology function of antisense intronic long noncoding RNA (Ai-lncRNA) is still unknown. Meanwhile, cancer patients with paclitaxel resistance have limited therapeutic options in the clinic. However, the potential involvement of Ai-lncRNA in paclitaxel sensitivity remains unclear in human cancer. Methods Whole transcriptome sequencing of 33 breast specimens was performed to identify Ai-lncRNA EGOT . Next, the role of EGOT in regulation of paclitaxel sensitivity was investigated. Moreover, the mechanism of EGOT enhancing autophagy sensitizes paclitaxel cytotoxicity via upregulation of ITPR1 expression by RNA-RNA and RNA-protein interactions was investigated in detail. Furthermore, upstream transcriptional regulation of EGOT expression was also investigated by co-immunoprecipitation and chromatin immunoprecipitation. Finally, clinical breast specimens in our cohort, TCGA and ICGC were applied to validate the role of EGOT in enhancing of paclitaxel sensitivity. Results EGOT enhances autophagosome accumulation via the up-regulation of ITPR1 expression, thereby sensitizing cells to paclitaxel toxicity. Mechanistically, on one hand, EGOT upregulates ITPR1 levels via formation of a pre-ITPR1/EGOT dsRNA that induces pre-ITPR1 accumulation to increase ITPR1 protein expression in cis . On the other hand, EGOT recruits hnRNPH1 to enhance the alternative splicing of pre-ITPR1 in trans via two binding motifs in EGOT segment 2 (324–645 nucleotides) in exon 1. Moreover, EGOT is transcriptionally regulated by stress conditions. Finally, EGOT expression enhances paclitaxel sensitivity via assessment of cancer specimens. Conclusions These findings broaden comprehensive understanding of the biology function of Ai-lncRNAs. Proper regulation of EGOT may be a novel synergistic strategy for enhancing paclitaxel sensitivity in cancer therapy.

Tumor cells can survive when detached from the extracellular matrix (ECM) or lose cell–cell connections, a phenomenon known as anoikis-resistance (AR). AR is closely associated with tumor cell metastasis and recurrence, enabling tumor cells to disseminate, migrate, and invade after detachment. To address this issue, a novel intervention method combining intraoperative hemostasis with multifunctional nanozyme driven-enhanced chemodynamic therapy (ECDT) has been proposed, which holds the potential to weaken the AR capability of tumor cells and suppress tumor recurrence. Here, a nanocomposite containing a dendritic mesoporous nanoframework with Cu 2+ was developed using an anion-assisted approach after surface PEG grafting and glucose oxidase (GOx) anchoring (DMSN-Cu@GOx/PEG). DMSN-Cu@GOx/PEG was further encapsulated in a thermal-sensitive hydrogel (H@DMSN-Cu@GOx/PEG). DMSN-Cu@GOx/PEG utilizes its high peroxidase (POD) activity to elevate intracellular ROS levels, thereby weakening the AR capability of bladder cancer cells. Additionally, through its excellent catalase (CAT) activity, DMSN-Cu@GOx/PEG converts the high level of hydrogen peroxide (H 2 O 2 ) catalyzed by intracellular GOx into oxygen (O 2 ), effectively alleviating tumor hypoxia, downregulating hypoxia-inducible factor-1α (HIF-1α) expression, inhibiting epithelial-mesenchymal transition (EMT) processes, and ultimately suppressing the migration and invasion of bladder cancer cells. Interestingly, in vivo results showed that the thermosensitive hydrogel H@DMSN-Cu@GOx/PEG could rapidly gel at body temperature, forming a gel film on wounds to eliminate residual tumor tissue after tumor resection surgery. Importantly, H@DMSN-Cu@GOx/PEG exhibited excellent hemostatic capabilities, effectively enhancing tissue coagulation during post-tumor resection surgery and mitigating the risk of cancer cell dissemination and recurrence due to surgical bleeding. Such hydrogels undoubtedly possess strong surgical application. Our developed novel nanosystem and hydrogel can inhibit the AR capability of tumor cells and prevent recurrence post-surgery. This study represents the first report of using dendritic mesoporous silica-based nanoreactors for inhibiting the AR capability of bladder cancer cells and suppressing tumor recurrence post-surgery, providing a new avenue for developing strategies to impede tumor recurrence after surgery. Graphical Abstract

Non-invasive optical imaging tools for early detecting anti-tumor immune responses are crucial for precision cancer immunotherapy. However, current probes often suffer from low imaging depth, single imaging channel, and inadequate quantification, hindering their in vivo applications. Here we develop a rare-earth-based NIR-II fluorescence ratiometric nanoprobe (DCGA) for in vivo real-time, precise, and non-invasive visualization of granzyme B (GzmB) activity, a key effector in T cell-mediated antitumor immunity, for early prediction of immunotherapy efficacy. The Nd/Er co-doped DCGA nanoprobe features NIR-II dual-emission ratiometric detection with self-calibrated target response signals, addressing challenges like uneven probe distribution and nonspecific signal interference. In vivo NIR-II ratiometric imaging reveals that GzmB activity well correlates with cytotoxic T cell responses and tumor growth, and can effectively distinguish responders from non-responders in both Hepa 1-6 tumor xenograft models and patient-derived xenograft models. Our DCGA probe shows promise for dynamic, real-time, non-invasive molecular imaging of T cell activation in deep tissues, offering effective support for tumor immunotherapy studies, precision medicine, and personalized diagnostics. Non-invasive optical imaging tools for early detection of anti-tumor immune responses are essential for precision cancer immunotherapy. Here, the authors report a rare-earth-based NIR-II fluorescence ratiometric nanoprobe (DCGA) for in vivo real-time, precise, and non-invasive visualization of granzyme B activity for early prediction of immunotherapy efficacy.

Background As the lethal bone tumor, osteosarcoma often frequently occurs in children and adolescents with locally destructive and high metastasis. Distinctive kinds of nanoplatform with high therapeutical effect and precise diagnosis for osteosarcoma are urgently required. Multimodal optical imaging and programmed treatment, including synergistic photothermal-chemodynamic therapy (PTT-CDT) elicits immunogenetic cell death (ICD) is a promising strategy that possesses high bio-imaging sensitivity for accurate osteosarcoma delineating as well as appreciable therapeutic efficacy with ignorable side-effects. Methods and results In this study, mesoporous Cu and Ce based oxide nanoplatform with Arg-Gly-Asp (RGD) anchoring is designed and successfully constructed. After loading with indocyanine green, this nanoplatform can be utilized for precisely targeting and efficaciously ablating against osteosarcoma via PTT boosted CDT and the closely following ICD stimulation both in vitro and in vivo. Besides, it provides off-peak fluorescence bio-imaging in the second window of near-infrared region (NIR II, 1000-1700 nm) and Magnetic resonance signal, serves as the dual-mode contrast agents for osteosarcoma tissue discrimination. Conclusion Tumor targeted Cu&Ce based mesoporous nanoplatform permits efficient osteosarcoma suppression and dual-mode bio-imaging that opens new possibility for effectively diagnosing and inhibiting the clinical malignant osteosarcoma.