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Abnormal levels of reactive oxygen species (ROS) and the hypoxic microenvironment within bone defects are important factors that impede bone repair processes. Herein, an innovative ultrasound‐modulatable hydrogel platform with selenoprotein‐mediated antioxidant effects to promote bone injury repair is presented. This hydrogel platform encapsulates oxygen‐enriched selene‐incorporated thin‐shell silicon within methacrylate gelatin (O2‐PSSG). The resultant construct orchestrates the modulation of the bone‐defect microenvironment, thereby expediting the course of bone regeneration. Ultrasound (US) is used to regulate the pore size of the hydrogel to release selenium‐containing nanoparticles and promote the in situ synthesis of efficient intracellular selenoproteins and hydrogen peroxide consumption. As expected, O2‐PSSG rapidly releases selenocystine ([Sec]2) under US control to scavenge reactive oxygen species and maintain the homeostasis of bone marrow mesenchymal stem cells (BMSCs). Over time, the action of the system by selenoprotein increases the activation of Wnt/β‐catenin pathways and promotes the differentiation of BMSCs. Consequently, O2‐PSSG potentiates the antioxidant proficiency of BMSCs both in vitro and in vivo, alleviates hypoxic environments, promotes osteogenic differentiation, and expedites cranial bone repair in rat models. In summary, this study suggests that the designed and constructed US‐responsive antioxidant hydrogel is a promising prospective strategy for addressing bone defects and fostering bone regeneration. [ABSTRACT FROM AUTHOR]

Malignant pleural effusion (MPE) poses a significant challenge in local treatment, primarily attributed to its intricate tumor immune microenvironment. The immunosuppression of natural killer (NK) cells within the microenvironment, exacerbated by selenium (Se) deficiency, constitutes a pivotal treatment bottleneck. Building upon prior investigations, this study delves into the impact and mechanisms of functionalized lentinan selenium nanoparticles (LET‐SeNPs) on NK cells in MPE, presenting a novel local treatment strategy for lung adenocarcinoma with malignant pleural effusion (MPE‐LA). The synergistic application of LET‐SeNPs serves to replenish Se levels in MPE, modulate NK cells, augment their quantity, restore and enhance their functionality. Additionally, LET‐SeNPs facilitate NK cells activation through the TrxR1‐IL18RAP‐pSTAT3 pathway, resulting in effective lung cancer cell eradication and reduced pleural effusion production. Furthermore, pre‐stimulation of NK cells by LET‐SeNPs, combined with CAR‐NK cell therapy, harnesses the innate immune system, exhibiting a potent anti‐tumor effect. This research introduces a compelling strategy to advance the clinical implementation of targeted nanomaterials or lead compounds with explicit targets and mechanisms, thereby enhancing NK cell therapy for comprehensive diagnosis and treatment of MPE. [ABSTRACT FROM AUTHOR]

Radiotherapy, as one of the most common strategies for clinical cancer treatment, suffers from failure due to the hypoxia, inflammation, and radiosensitivity difference of malignant tumors, side effects, and radioresistance. Heterojunction‐based radiosensitizers attract great attention to the lower excitation energy and remarkable catalytic activity as compared to typical transition metal radiosensitizers. However, the bio‐application of heterojunction radiosensitizers is in its infancy due to the challenges in structure engineering, rational energy band alignment, and ideal photogenerated carrier migration. Herein, a bimetallic metal‐organic framework (MOF)‐based heterojunction radiosensitizer is reasonably designed to enhance the radiodynamic therapeutic efficiency of Ru complex, and to activate natural killer (NK) cell‐mediated innate immune responses for promoted tumor immunotherapy. This study not only designs a novel bimetallic MOF‐based heterojunction structure but also elucidates the underlying action mechanisms in inhibiting cancer proliferation, which sheds light on the practicable design of radiosensitizers and the tumor combination treatment. [ABSTRACT FROM AUTHOR]

Activation of cuproptosis pathway has been reported to hold great potential in the application of tumor treatment. But the efficacy of cuproptosis seriously limited by the insufficient accumulation in the tumor sites. Therefore, herein based on the strong stabilization effects of the metalloid element selenium (Se) on copper (Cu), a photothermic Cu2‐xSe nanoparticle encapsulated with bioresponsive dimethyl maleic anhydride (DMMA@Cu2‐xSe) as a copper‐carrier to improve the copper accumulation in tumor is constructed, thus achieving cuproptosis‐driven enhancement of thermotherapy. This nanosystem exhibits the enhancement of tumor cellular uptake by a weak acid‐triggered charge‐switching ability. Next step, the exposed Cu2‐xSe is oxidized and releases divalent copper by high‐level oxide. Then, the abundant copper induces more dihydrolipoamide S‐acetyltransferase oligomerization to down‐regulate FDX1 and tricarboxylic acid cycle‐related proteins, which leads to inhibiting aerobic respiration. Cuproptosis‐induced mitochondrial damage further improves thermotherapy by up‐regulating reactive oxygen species (ROS). In addition, the generated ROS also promotes copper release to strengthen cuproptosis, and eventually improves tumor thermotherapy in turn. In general, DMMA@Cu2‐xSe with sequentially triggered copper‐release, efficient cuproptosis, and appropriate photothermal is a self‐enhanced nanoplatform for cuproptosis‐driven enhancement of thermotherapy. [ABSTRACT FROM AUTHOR]

Glucocorticoid (GC)‐induced osteoporosis (GIO) is a concurrent disease commonly appeared in chronic inflammatory and autoimmune disease patients. Stereoselective recognition between chiral drugs and homochiral biological molecules could directly affect their distribution, adhesion and transport. Herein, trace element selenium (Se) with bone formation‐regulating activity, is employed to construct cysteine‐decorated chiral nanoparticles (Cys@SeNPs) to attenuate GIO. Interestingly, comparing with the racemic (DL‐Cys@SeNPs) and D‐Cys@SeNPs, the L‐Cys@SeNPs displays higher uptake in osteoblast cells and could lessen reactive oxygen species overproduction to block dexamethasone (Dex)‐induced osteoblasts cells apoptosis. Intracellular L‐Cys@SeNPs could be predominantly transformed to selenocystine to upregulate the expression levels of antioxidative selenoproteins to effectively scavenge Dex‐induced excessive ROS accumulation in osteoblasts, and thus reduce the undesirable apoptosis through activating Wnt/β‐catenin pathway. Consistently, L‐Cys@SeNPs significantly alleviates the main osteoporosis symptoms of bone trabeculae destruction and decreased bone density in vivo, and also reduces the weight gain and fatty liver formation in Dex‐exposed mice, thus suppressing the overall side effects of Dex. This study not only demonstrates an effective strategy for treatment of GIO by using chiral Se nanomedicine, but also elucidates the important roles of selenoproteins in alleviating osteoporosis, which could help for future Se‐based drug design through chirality control engineering. [ABSTRACT FROM AUTHOR]

Developing radiosensitizers based on the characteristics of the tumor microenvironment can improve the effectiveness and overcome the bottleneck of cervical cancer radiotherapy. Herein, an in situ synthesis strategy is demonstrated by using a highly bioactive zeolitic imidazolate framework to cap Mn3O4 and folic acid as targeting molecules (FA‐Mn3O4@ZIF‐8) to achieve enhanced radiosensitization against cervical cancer. As expected, the ZIF‐8 cap on the surface of Mn3O4 responds more effectively to X‐rays. Meanwhile, by facilitating the presence of oxygen vacancies and valence transition of manganese on the surface of Mn3O4, the ZIF‐8 cap on Mn3O4 can increase the catalytic capacity for hydrogen peroxide (H2O2) and glutathione as well as produce more singlet oxygen under X‐ray, alleviate hypoxia within the tumor microenvironment, and increase reactive oxygen species production. Moreover, FA‐Mn3O4@ZIF‐8 shows excellent radiotherapy‐sensitizing properties in vitro and in vivo by promoting DNA damage and apoptosis. Collectively, this study suggests that designing and construction of X‐ray responsive nanoradiosensitizers could be a good way for future clinical radiotherapy of malignant cervical cancer. [ABSTRACT FROM AUTHOR]

In the article "Selenoprotein-Regulated Hydrogel for Ultrasound-Controlled Microenvironment Remodeling to Promote Bone Defect Repair," Hongmei Liu, Tianfeng Chen, and their colleagues introduce an innovative hydrogel platform that can be controlled by ultrasound to promote the repair of bone injuries. The hydrogel contains a thin-shell silicon incorporated with selene and oxygen, which is released under ultrasound control. This process helps to remodel the microenvironment of bone defects by addressing hypoxia and high levels of reactive oxygen species. The researchers believe that this hydrogel platform shows promising potential for promoting bone regeneration. [Extracted from the article]

O2‐delivering nanosystems have been used to antagonize hypoxia‐induced tumor therapeutic resistance. However, short‐time oxygen storage is still a bottleneck for these O2‐delivering nanosystems, which results in a decrease in blood circulation time and accumulation of oxygen in tumors, thus reducing the tumor therapeutic efficacy. Herein, a long‐term oxygen storage nanosystem (O2‐PIr@Si@PDA) is designed to overcome hypoxia for the treatment of nasopharyngeal carcinoma. This nanosystem is constructed by using perfluorooctyl bromide (PFOB) core as the oxygen carrier, functionalized with an oxygen sensitive probe (Ir(III) complex) and subsequently enclosed with an ultrathin‐walled silica shell. Due to the silica shell, this nanosystem can store oxygen for longer than 7 days. The oxygen in the O2‐PIr@Si@PDA nanosystem can be released quickly with the temperature‐responsive rupture of the silicon shell under near‐infrared (NIR) irradiation. The oxygen storage and release can be self‐monitored using the Ir(III) complex with its luminescence effect. As expected, this multifunctional nanosystem in combination with NIR irradiation not only inhibits tumor growth by alleviating hypoxia, but also enhances the effect of oxygen‐sensitized radiotherapy against nasopharyngeal carcinoma. Taken together, this study offers a novel strategy for designing long‐term oxygen storing nanosystem to relieve tumor hypoxia, thus improving the precise cancer therapeutic efficacy. [ABSTRACT FROM AUTHOR]

Nanorod-based drug delivery systems have attracted great interest because of their enhanced cell internalization capacity and improved drug loading property. Herein, novel mesoporous silica nanorods (MSNRs) with different lengths are synthesized and used as nanocarriers to achieve higher drug loading and anticancer activity. As expected, MSNRs-based drug delivery systems can effectively enhance the loading capacity of drugs and penetrate into tumor cells more rapidly than spherical nanoparticles due to their greater surface area and trans-membrane transporting rates. Interestingly, these tailored MSNRs also enhance the cellular uptake of doxorubicin (DOX) in cancer cells, thus significantly enhancing its anticancer efficacy for hundreds of times by inducing of cell apoptosis. Internalized MSNRs-DOX triggers intracellular reactive oxygen species (ROS) overproduction, which subsequently activates p53 and mitogen-activated protein kinases (MAPKs) pathways to promote cell apoptosis. MSNRs-DOX nanosystem also shows prolonged blood circulation time in vivo. In addition, MSNRs-DOX significantly inhibits in vivo tumor growth in nude mice model and effectively reduced its in vivo toxicity. Therefore, this study provides an effective and safe strategy for designing chemotherapeutic agents for precise cancer therapy. [ABSTRACT FROM AUTHOR]

Tellurium (Te) is an important semiconductor material with low band-gap energy, which has attracted considerable attention in recent years, due to its special chemical and physical properties and wide potential in electrochemistry, optoelectronics, and biological fields. This study demonstrates a facile and high-yield synthesis strategy of Te nanorods (PTW-TeNRs) decorated by polysaccharide-protein complex, which can achieve simultaneous chemo-photothermal combination therapy against cancers. PTW-TeNRs alone possess high stability under physiological conditions, potent anticancer activities through induction of reactive oxygen species overproduction, and high selectivity among tumor and normal cells. More importantly, they exhibit strong near-infrared (NIR) absorbance and good photothermal conversion ability from NIR light to heat energy. Furthermore, in combination with NIR laser irradiation, PTW-TeNRs exhibit excellent chemo-photothermal efficiency and low toxicity as evidenced by highly efficient tumor ablation ability, but show no obvious histological damage to the major organs. Taken together, this study provides a valid tactic for facile synthesis of multifunctional tellurium nanorods for efficient and combinational cancer therapy. [ABSTRACT FROM AUTHOR]

Cervical cancers, radiotherapy sensitizers, X-ray-responses, zeolitic imidazolate frameworks Keywords: cervical cancers; radiotherapy sensitizers; X-ray-responses; zeolitic imidazolate frameworks EN cervical cancers radiotherapy sensitizers X-ray-responses zeolitic imidazolate frameworks 1 1 1 03/27/23 20230323 NES 230323 B Cervical Cancer-Targeting Radiosensitization b In article number 2213364, Xueqiong Zhu, Tianfeng Chen, and co-workers report zeolitic imidazolate framework-capped Mn SB 3 sb O SB 4 sb nanoparticles modified with folic acid with X-ray response properties. This nanoparticle possesses a high oxygen vacancies rate and Mn SP 3+ sp ratio, promoting H SB 2 sb O SB 2 sb and glutathione degradation, producing more singlet oxygen under X-ray, increasing reactive oxygen species level, and alleviating hypoxia within the tumor microenvironment. [Extracted from the article]

The rational design of cancer-targeted and bioresponsive drug delivery vehicles can enhance the anticancer efficacy of conventional chemotherapeutics and reduce their adverse side effects. However, the complexity of precise delivery and the ability to trigger drug release in specific tumor sites remain a challenging puzzle. Here, a sequentially triggered nanosystem composed of HER2 antibody with disulfide linkage as a surface decorator (HER2@NPs) is constructed for precise drug delivery and the simultaneous inhibition of cancer growth, migration, and invasion. The nanosystem actively accumulates in cancer cells, undergoes self-immolative cleavage in response to biological thiols, and is degraded to form small nanoparticles. After internalization by receptor-mediated endocytosis, the nanoparticles further disassemble under acidic conditions in the presence of lysozymes and cell lysates, leading to sequentially triggered drug release. The released payload triggers overproduction of reactive oxygen species and activates p53 and MAPKs pathways to induce cancer cell apoptosis. Moreover, HER2@NPs markedly suppress the migration and invasion of human bladder cancer cells at nontoxic concentrations. HER2@NPs demonstrate potent in vivo anticancer efficacy, but show no obvious histological damage to the major organs. Taken together, this study provides a valid tactic for the rational design of sequentially triggered nanosystems for precise drug delivery and cancer therapy. [ABSTRACT FROM AUTHOR]

Mesoporous silica nanoparticles (MSNs) have been well-demonstrated as excellent carriers for anticancer drug delivery. Presented here is a cancer-targeted MSNs drug delivery system that allows the direct fluorescence monitoring of the cellular uptake and localization of theranostic agents in cancer cells. Specifically, the anticancer action mechanisms of RGD peptide-functionalized MSNs carrying ruthenium polypyridyl complexes (RuPOP@MSNs) are elucidated in detail. RGD peptide surface decoration significantly enhances the cellular uptake of the nanoparticles through receptor-mediated endocytosis, and increases the selectivity between cancer and normal cells. RuPOP@MSNs exhibits unprecedented enhanced cytotoxicity toward cancer cells overexpressing integrin receptor, which is significantly higher than that of free RuPOP, through induction of apoptosis. The important contribution of extrinsic pathway to cell apoptosis is confirmed by increase in expression levels of death receptors, activation of caspase-8 and truncation of Bid. The internalized nanoparticles release free RuPOP into the cytoplasm, where they modulate the phosphorylation of p53, AKT, and MAPKs pathways to promote cell apoptosis. Moreover, the strong autofluorescence of RuPOP permits the direct monitoring of drug delivery, and extends the power of theranostics to subcellular level. Taken together, this study provides an effective strategy for the design and development of cancer-targeted theranostic agents. [ABSTRACT FROM AUTHOR]

Mater. i B 2017 b , 1703313 In the initially published version of this article, the "Heart" image of the DOX group in Figure 7A was incorrect. The correct Figure 7A is as follows: GLO:OKZ/23jul20:adfm202004479-fig-0001.jpg PHOTO (COLOR): 7 Evaluation of MSNRs-DOX caused systemic toxicities in vivo. (B) - (E) Blood biochemistry analysis of the indices of LDH, CK, UA and AST in mice treated with MSNRs-DOX (4 mg kg-1) at 21 days of treatment. [Extracted from the article]

Nanoparticulate chemotherapeutics hold great potential for inducing reactive oxygen species (ROS) overproduction and exerting antihypoxic effects for efficient cancer radiotherapy. However, previous strategies for designing smart radiosensitizers necessitate the multistep incorporation of nanomaterials to achieve valuable radiosensitive outcomes, which causes unpredictable safety issues including poor decomposition and undefined biotransformations. Ultrathin antimonene nanoparticles (AMNPs) are demonstrated as new radiosensitizers that achieve an efficient radiochemotherapeutic effect through the induction of a strong oxidative stress response and their significantly high radiotoxicity in vivo. Analyzing the irradiation process of AMNPs indicates that irradiation accelerates photoelectron generation and the valence transition to toxic Sb2O3, leading to cancer cell apoptosis and S‐phase arrest. The tumor regression activity and concealed biotoxicity of the AMNPs in a melanoma mouse model enhance the applicability of antimonene to overcoming radioresistance by increasing ROS generation and normoxia. This new technology can extend the applications of antimonene as an effective radiosensitizer and can promote its clinical translation for tunable and effective radiosensitization in the future. [ABSTRACT FROM AUTHOR]

Highlights from the article: Cancer Immunotherapy: Designing Bioinspired 2D MoSe2 Nanosheet for Efficient Photothermal-Triggered Cancer Immunotherapy with Reprogramming Tumor-Associated Macrophages (Adv. Funct. Keywords: 2D materials; cancer immunotherapy; photothermal therapy; reprogramming; tumor-associated macrophages 2D materials, cancer immunotherapy, photothermal therapy, reprogramming, tumor-associated macrophages.

Nonspecific absorption and clearance of nanomaterials during circulation is the major cause for treatment failure in nanomedicine‐based cancer therapy. Therefore, herein bioinspired red blood cell (RBC) membrane is employed to camouflage 2D MoSe2 nanosheets with high photothermal conversion efficiency to achieve enhanced hemocompatibility and circulation time by preventing macrophage phagocytosis. RBC–MoSe2‐potentiated photothermal therapy (PTT) demonstrates potent in vivo antitumor efficacy, which triggers the release of tumor‐associated antigens to activate cytotoxic T lymphocytes and inactivate the PD‐1/PD‐L1 pathway to avoid immunologic escape. Furthermore, in the ablated tumor microenvironment, the tumor‐associated macrophages are effectively reprogrammed to tumoricidal M1 phenotype to potentiate the antitumor action. Taken together, this biomimetic functionalization thus provides a substantial advance in personalized PTT‐triggered immunotherapy for clinical translation. [ABSTRACT FROM AUTHOR]

A smart strategy for rational design of a carbon nanotubebased nanosystem Se@CNTs with surface charge flipping and targeted ability for precise chemo‐photothermal synergistic therapy of triple‐negative breast cancers is reported by Tianfeng Chen and co‐workers in article number 1805225. Upon NIR laser irradiation, Se@CNTs exhibits good photothermal conversion ability, and excellent chemo‐photothermal efficiency with high safety potency. [ABSTRACT FROM AUTHOR]

Owing to the highly malignant and invasive innate character of triple‐negative breast cancers (TNBCs), it is easy to relapse after chemotherapy; thus, there are still no effective and specific targeted therapies. In this study, a carbon nanotube (CNT)‐based nanosystem Se@CNTs with surface charge flipping and targeted ability is rationally designed and successfully synthesized for precise chemo‐photothermal synergistic therapy of TNBCs. The acid‐labile β‐carboxylic acid group is used to reversibly functionalize the amine groups, thus forming charge‐reversal nanoparticles to enhance the bioresponsive cellular uptake. The internalized Se@CNTs combined with laser irradiation induces reactive oxygen species (ROS) overproduction, which activates apoptosis‐related proteins to trigger cancer cell apoptosis synergistically. Meanwhile, Se@CNTs also suppresses the invasion and migration of TNBC cells by regulating the related signaling pathways. Importantly, in combination with laser irradiation, Se@CNTs effectively inhibits the tumor growth, as demonstrated by the high tumor ablation activity in vivo through chemo‐phototherapy, but shows no significant histological change in the main organs. Taken together, this study provides a strategy for rational design of next‐generation nanomedicines for precise chemo‐photothermal synergistic therapy of malignant TNBCs. A novel carbon nanotube (CNT)‐based nanosystem is rationally designed to achieve enhanced chemo‐photothermal treatments of triple‐negative breast cancer (TNBC) tumor, which triggers cancer cell apoptosis and suppresses cell invasion and migration by regulating related signaling pathways. This study provides an effective strategy for rational design of next‐generation nanomedicines for precise chemo‐photothermal synergistic therapy of malignant cancers. [ABSTRACT FROM AUTHOR]

A valid tactic for facile synthesis of multifunctional tellurium nanorods to achieve simultaneous chemophotohermal combination cancer therapy is reported by Tianfeng Chen and co‐workers in article number 1701388. In combination with near‐infrared (NIR) laser irradiation, the tellurium nanorods exhibit good photothermal conversion ability from NIR light to heat energy, and show excellent chemo‐photothermal efficiency and low toxicity to normal organs. [ABSTRACT FROM AUTHOR]

A precise drug delivery system for simultaneously inhibiting cancer growth, migration, and invasion is presented by Tianfeng Chen and co‐workers on page 7775. The sequentially triggered nanosystem decorated by HER2 antibody with disulfide linkages provides a valid tactic for the rational design of smart nanosystems for drug delivery and therapy. [ABSTRACT FROM AUTHOR]

In this study, T. Chen and co‐workers present a cancer‐targeted MSN drug‐delivery system carrying ruthenium complexes (RuPOP@MSNs), that allows the direct fluorescence monitoring of the cellular uptake and localization of theranostic agents in cancer cells. On page 2754 the nanoparticles exhibit unprecedented enhanced cytotoxicity toward cancer cells overexpressing integrin receptors through the induction of apoptosis. Moreover, the strong autofluorescence of Ru complex extends the power of theranostics to a subcellular level. [ABSTRACT FROM AUTHOR]