Biosynthesis of fungus-based oral selenium microcarriers for radioprotection and immuno-homeostasis shaping against radiation-induced heart disease.

Radiation-induced heart disease (RIHD), characterized by severe oxidative stress and immune dysregulation, is a serious condition affecting cancer patients undergoing thoracic radiation. Unfortunately, clinical interventions for RIHD are lacking. Selenium (Se) is a trace element with excellent antioxidant and immune-modulatory properties. However, its application in heart radioprotection remains challenging. Herein, we developed a novel bioactive Cordyceps militaris-based Se oral delivery system (Se@CM), which demonstrated superior radioprotection effects in vitro against X-ray-induced damage in H9C2 cells through suppressing excessive ROS generation, compared to the radioprotectant Amifostine. Moreover, Se@CM exhibited exceptional cardioprotective effects in vivo against X-ray irradiation, reducing cardiac dysfunction and myocardial fibrosis by balancing the redox equilibrium and modulating the expression of Mn-SOD and MDA. Additionally, Se@CM maintained immuno-homeostasis, as evidenced by the upregulated population of T cells and M2 macrophages through modulation of selenoprotein expression after irradiation. Together, these results highlight the remarkable antioxidant and immunity modulation properties of Se@CM and shed light on its promising application for cardiac protection against IR-induced disease. This research provides valuable insights into developing effective strategies for preventing and managing RIHD.

Selenium promotes immunogenic radiotherapy against cervical cancer metastasis through evoking P53 activation.

Radiotherapy is still the recommended treatment for cervical cancer. However, radioresistance and radiation-induced side effects remain one of the biggest clinical problems. Selenium (Se) has been confirmed to exhibit radiation-enhancing effects for cancer treatment. However, Se species dominate the biological activities and which form of Se possesses better radiosensitizing properties and radiation safety remains elusive. Here, different Se species (the valence state of Se ranged from - 2, 0, +4 to + 6) synergy screen was carried out to identify the potential radiosensitizing effects and radiation safety of Se against cervical cancer. We found that the therapeutic effects varied with the changes in the Se valence state. Sodium selenite (+4) displayed strong cancer-killing effects but also possessed severe cytotoxicity. Sodium selenate (+6) neither enhanced the killing effects of X-ray nor possessed anticancer activity by its alone treatment. Although nano-selenium (0), especially Let-SeNPs, has better radiosensitizing activity, the - 2 organic Se, such as selenadiazole derivative SeD (-2) exhibited more potent anticancer effects and possessed a higher safe index. Overall, the selected Se drugs were able to synergize with X-ray to inhibit cell growth, clone formation, and cell migration by triggering G2/M phase arrest and apoptosis, and SeD (-2) was found to exhibit more potent enhancing capacity. Further mechanism studies showed that SeD mediated p53 pathway activation by inducing DNA damage through promoting ROS production. Additionally, SeD combined with X-ray therapy can induce an anti-tumor immune response in vivo. More importantly, SeD combined with X-ray significantly inhibited the liver metastasis of tumor cells and alleviated the side effects caused by radiation therapy in tumor-bearing mice. Taken together, this study demonstrates the radiosensitization and radiation safety effects of different Se species, which may shed light on the application of such Se-containing drugs serving as side effects-reducing agents for cervical cancer radiation treatment.

Ecological membrane for slope engineering based on red bed soil.

Ecological slope protection projects (such as the reinforcement of low slopes by plants and ecological restorations of the soil of high steep rocky slopes) are essential for restoring the natural environment. In this study, red bed soil and composite polymer adhesive materials were used to develop an ecological membrane for application in slope ecological protection. The basic physical and mechanical properties of the ecological membranes with different material percentages were studied through tensile strength test and viscosity test, the effect of different material percentages on the properties of ecological membranes was studied, and the soil protection performance and ecological restoration performance were studied through anti-erosion and plant growth tests. The results show that the ecological membrane is soft and tough, with high tensile strength. The addition of the red bed soil can enhance the strength of the ecological membrane, and the ecological membrane with 30% red bed soil has the highest tensile strength. The ecological membrane has considerable tensile deformation capability and viscosity, and up to 100% by mass, the more composite polymer adhesive materials added, the greater the tensile deformation capability and viscosity. And the ecological membrane can enhance the anti-erosion performance of the soil. This study clarifies the development and technology of the ecological membrane, reveals the effect of different material percentages on the properties of ecological membrane, and analyzes the slope ecological protection mechanism of the ecological membrane, thereby providing theoretical and data support for its development, improvement, and application.

Protective effect of spore oil-functionalized nano-selenium system on cisplatin-induced nephrotoxicity by regulating oxidative stress-mediated pathways and activating immune response.

In clinical practice, cisplatin is the most commonly used chemotherapy drug to treat a range of malignancies. Severe ROS-regulated nephrotoxicity, however, restricts its applicability. Currently, the main mechanisms leading to cisplatin-induced nephrotoxicity in clinical settings involve hydration or diuresis. However, not all patients can be treated with massive hydration or diuretics. Therefore, it is crucial to develop a treatment modality that can effectively reduce nephrotoxicity through a foodborne route. Selenium has been reported to have strong antioxidant as well as anticancer effects when administered as spore oil. Herein, we established cellular and animal models of cisplatin-induced nephrotoxicity and synthesized spore oil-functionalized nano-selenium (GLSO@SeNPs). We found that GLSO@SeNPs inhibit the mitochondrial apoptotic pathway by maintaining oxidative homeostasis and regulating related signaling pathways (the MAPK, caspase, and AKT signaling pathways). In vivo, GLSO@SeNPs could effectively improve cisplatin-induced renal impairment, effectively maintaining oxidative homeostasis in renal tissues and thus inhibiting the process of renal injury. In addition, GLSO@SeNPs were converted into selenocysteine (SeCys2), which may exert protective effects. Furthermore, GLSO@SeNPs could effectively modulate the ratio of immune cells in kidneys and spleen, reducing the proportions of CD3+CD4+ T cells, CD3+CD8+ T cells, and M1 phenotype macrophages and increasing the proportion of anti-inflammatory regulatory T cells. In summary, in this study, we synthesized food-derived spore oil-functionalized nanomaterials, and we explored the mechanisms by which GLSO@SeNPs inhibit cisplatin-induced nephrotoxicity. Our study provides a basis and rationale for the inhibition of cisplatin-induced nephrotoxicity by food-derived nutrients.

Experimental Study on Ecological Performance Improvement of Sprayed Planting Concrete Based on the Addition of Polymer Composite Material.

Sprayed planting concrete (SPC) can be used for the ecological restoration of rocky steep slopes. It is a kind of outside-soil material with excellent soil and slope stabilization performance, and plants can grow in SPC, thus achieving harmony between engineering stability and ecological restoration and improving the landscape and ecosystem. The addition of cement is the key to allowing SPC to achieve slope stabilization and prevent soil erosion. However, the addition of cement can cause SPC to have high alkalinity, overheating (cement generates hydration heat), and excessive hardening, which are not conducive to the growth of plants and can lead to poor ecological performance of SPC for slope ecological restoration. We studied the improvement of the ecological performance of SPC by using a polymer composite material composed of a polymer adhesive material and a polymer water-retaining material. This paper studied the improvement effects of the polymer composite material on the ecological performance of SPC used in slope ecological restoration through a laboratory erosion resistance test and a plant growth test. The results showed that SPC with the addition of polymer composite material can reduce its cement content by about 50% while still retaining excellent erosion resistance performance when it is used in slope ecological restoration. Additionally, the plant germination rates and plant heights when using the SPC improved by polymer composite material were increased by 190% and 110%, respectively. These results show that polymer composite material can significantly improve the ecological performance of SPC and effectively improve its slope ecological restoration effects. This study provides theoretical and technical support for the application of SPC in ecological restoration on rocky steep slopes.

Mechanical properties and mechanism of soil treated with nano-aqueous adhesive (NAA).

The loose structure and low mechanical strength of the surface soil make it vulnerable to damage under erosion conditions. Slope ecological protection is one of the effective methods to improve the stability of slope soil. Although it has been proved that polymer modified materials can effectively improve the soil properties and the environmental protection effect of slope, so far, the improvement mechanism has not been fully understood, especially the chemical mechanism of the material on the enhancement of soil mechanical properties is not clear. In the present study, the effects of nano-aqueous adhesive (NAA) on unconfined compressive strength, shear strength and aggregate characteristics of soil were studied by a series of laboratory experiments. The results show that NAA can increase the strength, aggregate number and stability of the soil, to effectively improve the stability of surface soil. In addition, through infrared spectroscopy and SEM test, it was found that NAA molecules were mainly distributed in the interlayer position of flaky clay minerals, mainly connected with clay minerals through hydrogen bonds, thereby effectively enhancing the cohesion of soil particles.

Gadolinium(III) Porphyrinoid Phototheranostics.

Molecular phototheranostics as an emerging field of modern precision medicine has recently attracted increasing research attention owing to non-invasiveness, high precision, and controllable nature of light. In this work, we reported promising gadolinium (Gd3+ ) porphyrinoids as phototheranostic agents for magnetic resonance imaging (MRI) and photodynamic therapy (PDT). The synthesized Gd-1-4-Glu featured with meso-glycosylation and ß-lactonization to endow good biocompatibility and improved photophysical properties. In particular, ß-lactonization of glycosylated Gd3+ porphyrinoids substantially red-shifted Q band absorption to near-infrared (NIR) region and boosted generation of reactive oxygen species including 1 O2 , and some radical species that engaged in both type II and type I PDT pathways. In addition, the number and regioisomerism of ß-oxazolone moieties was observed to play an essential role in improving longitude relaxivity (r1 ) of Gd-1-4-Glu of up to 4.3±0.2 mM-1 s-1 by affecting environmental water exchange. Taking Gd-4-Glu as a promising complex, we further achieved real-time T1 -weighted MRI and PDT on HeLa tumour mice in vivo, revealing the appealing potential of Gd3+ porphyrinoids in phototheranostics.

A Universally EDTA-Assisted Synthesis of Polytypic Bismuth Telluride Nanoplates with a Size-Dependent Enhancement of Tumor Radiosensitivity and Metabolism In Vivo.

Bismuth telluride (Bi2Te3) is an available thermoelectric material with the lowest band gap among bismuth chalcogenides, revealing a broad application in photocatalysis. Unfortunately, its size and morphology related to a radio-catalysis property have rarely been explored. Herein, an ethylenediaminetetraacetic acid (EDTA)-assisted hydrothermal strategy was introduced to synthesize polytypic Bi2Te3 nanoplates (BT NPs) that exhibit size-dependent radio-sensitization and metabolism characteristics in vivo. By simply varying the molar ratio of EDTA/Bi3+ during the reaction, BT NPs with different sizes and morphologies were obtained. EDTA acting as chelating agent and "capping" agent contributed to the homogeneous growth of BT NPs by eliminating dangling bonds and reducing the surface energy of different facets. Further analyzing the size-dependent radio-sensitization mechanism, larger-sized BT NPs generated holes that preferentially catalyzed the conversion of OH- to ·OH when irradiated with X-rays, while the smaller-sized BT NPs exhibited faster decay kinetics producing higher 1O2 levels to enhance radiotherapy effects. A metabolomic analysis revealed that larger-sized BT NPs were oxidized into Bi(Ox) in the liver via a citrate cycle pathway, whereas smaller-sized BT NPs accumulated in the kidney and were excreted in urine in the form of ions by regulating the metabolism of glutamate. In a cervical cancer model, BT NPs combined with X-ray irradiation significantly antagonized tumor suppression through the promotion of apoptosis in tumor cells. Consequently, in addition to providing a prospect of BT NPs as an efficient radio-sensitizer to boost the tumor radiosensitivity, we put forth a strategy that can be universally applied in synthesizing metal chalcogenides for catalysis-promoted radiotherapy.

The investigation and bioorthogonal anticancer activity enhancement of a triphenylphosphine-labile prodrug of seleno-combretastatin-4.

Here, a triphenylphosphine (TPP)-labile prodrug of seleno-combretastatin-4 (CSeD) was designed and synthesized. A detailed investigation revealed that CSeD, which was shown to be very safe in circulating blood, could react with TPP to release CA-4 and a selenodiazole derivative, with accompanying powerful anticancer and antiangiogenesis effects, as well as radiosensitization properties.

Biomedical Application of Reactive Oxygen Species-Responsive Nanocarriers in Cancer, Inflammation, and Neurodegenerative Diseases.

Numerous pathological conditions, including cancer, inflammatory diseases, and neurodegenerative diseases, are accompanied by overproduction of reactive oxygen species (ROS). This makes ROS vital flagging molecules in disease pathology. ROS-responsive drug delivery platforms have been developed. Nanotechnology has been broadly applied in the field of biomedicine leading to the progress of ROS-responsive nanoparticles. In this review, we focused on the production and physiological/pathophysiological impact of ROS. Particular emphasis is put on the mechanisms and effects of abnormal ROS levels on oxidative stress diseases, including cancer, inflammatory disease, and neurodegenerative diseases. Finally, we summarized the potential biomedical applications of ROS-responsive nanocarriers in these oxidative stress diseases. We provide insights that will help in the designing of new ROS-responsive nanocarriers for various applications.

TRPM8-regulated calcium mobilization plays a critical role in synergistic chemosensitization of Borneol on Doxorubicin.

Background: Lung cancer has a high mortality rate and is resistant to multiple chemotherapeutics. Natural Borneol (NB) is a monoterpenoid compound that facilitates the bioavailability of drugs. In this study, we investigated the effects of NB on chemosensitivity in the A549 human lung adenocarcinoma cell line and to elucidate therapeutic molecular target of NB. Methods: The chemosensitivity effects of NB in A549 cells were examined by MTT assay. The mechanism of NB action was evaluated using flow cytometry and Western blotting assays. Surface plasmon resonance (SPR) and LC-MS combined analysis (MS-SPRi) was performed to elucidate the candidate molecular target of NB. The chemosensitizing capacity of NB in vivo was assessed in nude mice bearing A549 tumors. Results: NB pretreatment sensitized A549 cells to low doxorubicin (DOX) dosage, leading to a 15.7% to 41.5% increase in apoptosis. This increase was correlated with ERK and AKT inactivation and activation of phospho-p38 MAPK, phospho-JNK, and phosphor-p53. Furthermore, this synergism depends on reactive oxygen species (ROS) generation. MS-SPRi analysis revealed that transient receptor potential melastatin-8 (TRPM8) is the candidate target of NB in potentiating DOX killing potency. Genetically, TRPM8 knock-down significantly suppresses the chemosensitizing effects of NB and inhibits ROS generation through restraining calcium mobilization. Moreover, pretreatment with NB synergistically enhances the anticancer effects of DOX to delay tumor progression in vivo. Conclusions: These results suggest that TRPM8 may be a valid therapeutic target in the potential application of NB, and show that NB is a chemosensitizer for lung cancer treatment.

Boosting Natural Killer Cell-Based Cancer Immunotherapy with Selenocystine/Transforming Growth Factor-Beta Inhibitor-Encapsulated Nanoemulsion.

Natural killer (NK) cell-based immunotherapy represents a promising strategy to overcome the bottlenecks of cancer treatment. However, the therapeutic efficacy is greatly limited by downregulation of recognition ligands on the tumor cell surface, and the immunosuppressive effects can be thwarted by the tumor microenvironment such as secretion of transforming growth factor-beta (TGF-ß), which could stunt the NK cell-mediated immune response. To overcome these limitations, herein we developed a nanoemulsion system (SSB NMs) to co-deliver TGF-ß inhibitor and selenocysteine (SeC) to achieve amplified anticancer efficacy. SSB NMs significantly enhanced the lytic potency of NK92 cells by 2.1-fold. Moreover, a subtoxic dose of SSB NMs effectively sensitized MDA-MB-231 triple-negative breast cancer (TNBC) cells to NK cells derived from seven clinical patients, resulting in an up to 13.8-fold increase in cancer lysis. Mechanistic studies reveal that the sensitizing effects relied on natural killer group 2, member D (NKG2D)/NKG2D ligands (NKG2DLs) signaling with the involvement of DNA damage response. SSB NMs also effectively restrained TGF-ß/TGF-ß RI/Smad2/3 signaling, which thus enhanced NKG2DL expression on tumor cells and stimulated NKG2D surface expression on NK92 cells, ultimately contributing to the enhanced immune response. Furthermore, SSB NMs sustained release of SeC and TGF-ß inhibitor and synergized with NK92 cells to induce significant anticancer effects in vivo. Together, this study not only demonstrates a simple strategy for the design of a nanoemulsion to co-deliver synergistic drugs but also sheds light on the application and action mechanisms in NK cell adaptive therapy against breast cancer, especially TNBCs.

Rational design and action mechanisms of chemically innovative organoselenium in cancer therapy.

Organo-seleno compounds (org-Se) have been widely used in antitumor, antiviral, and antiinflammatory therapy; antioxidation and other biological fields. As such, they have made an important contribution to overcoming various kinds of diseases, and researchers are increasingly attracted to org-Se's synthesis and functional design. This review is mainly focused on the design and synthesis of various kinds of org-Se, followed by their anticancer mechanisms such as the mitochondria mediated pathway induced by ROS, death receptor mediated pathways involving p53 phosphorylation, and the activation of the AMPK pathway to promote apoptosis. Org-Se also serves as a sensitizer in chemotherapy and radiotherapy, and an antagonist against the cytotoxic effects induced by chemotherapeutic agents. Finally, we will summarize the development of cancer-targeted org-Se containing complexes, and nanotechnology-based org-Se for anticancer application. This review could provide information for the future design of chemically innovative org-Se with anticancer potential, and shed light on the discovery of nanomaterial-based pharmaceuticals to improve drug development and formation.

Selenium-containing ruthenium complex synergizes with natural killer cells to enhance immunotherapy against prostate cancer via activating TRAIL/FasL signaling.

Natural killer (NK) cells-based therapy has been used widely for cancer treatment in clinic trails. However, the immunotherapeutic efficacy of this method has been greatly hindered by tumor evasion and diminished activities of NK cells. In the present study, a selenium (Se)-bearing ruthenium (Ru) complex (RuSe) was designed that could synergistically potentiate NK cell-mediated killing against prostate cancer cells. As expected, pretreatment of cancer cells with subtoxic doses of RuSe effectively augmented the lysis potency of NK cells, with up to 2.46-fold enhancement than NK cells alone, against PC3 cells. More importantly, low concentrations of RuSe could augment the tumor destroying potency of NK cells derived from 10 clinical patients, with the enhancement range from 0.78- to 11.9-fold against PC3 cells and 0.67- to 3.8-fold against LNCAP cells. Mechanistic studies revealed that the sensitizing effect of RuSe primarily depended on TRAIL/TRAIL-R and Fas/FasL-mediated signaling. Furthermore, the increased expression level of these ligands highly relied on ROS overproduction-triggered DNA damage and the downstream ATM and ATR pathways. Furthermore, RuSe potently activated and synergized with NK cells to restrain tumor growth in vivo without causing toxic side effects on major organs. Taken together, the current study not only provides a strategy for application of metal complexes in chemo-immunotherapy but also sheds light on the potential roles and mechanisms of action on such Se-containing drugs as efficient immune-sensitizing agents for NK cell-based immunotherapy.

Functionalization and cancer-targeting design of ruthenium complexes for precise cancer therapy.

The successful clinical application of the three generation platinum anticancer drugs, cisplatin, carboplatin and oxaliplatin, has promoted research interest in metallodrugs; however, the problems of drug resistance and adverse effects have hindered their further application and effects. Thus, scientists are searching for new anticancer metallodrugs with lower toxicity and higher efficacy. The ruthenium complexes have emerged as the most promising alternatives to platinum-based anticancer agents because of their unique multifunctional biochemical properties. In this review, we first focus on the anticancer applications of various ruthenium complexes in different signaling pathways, including the mitochondria-mediated pathway, the DNA damage-mediated pathway, and the death receptor-mediated pathway. We then discuss the functionalization and cancer-targeting designs of different ruthenium complexes in conjunction with other therapies such as photodynamic therapy, photothermal therapy, radiosensitization, targeted therapy and nanotechnology for precise cancer therapy. This review will help in designing and accelerating the research progress regarding new anticancer ruthenium complexes.

Iron(II)-Polypyridyl Complexes Inhibit the Growth of Glioblastoma Tumor and Enhance TRAIL-Induced Cell Apoptosis.

A promising cancer-targeting agent for the induction of apoptosis in tumor necrosis factor (TNF) proteins, the TNF-related apoptosis-inducing ligand (TRAIL) ligand, has found limited applications in the treatment of cancer cells, owing to its resistance by cancer cell lines. Therefore, the rational design of anticancer agents that could sensitize cancer cells towards TRAIL is of great significance. Herein, we report that synthetic iron(II)-polypyridyl complexes are capable of inhibiting the proliferation of glioblastoma cancer cells and efficiently enhancing TRAIL-induced cell apoptosis. Mechanistic studies demonstrated that the synthesized complexes induced cancer-cell apoptosis through triggering the activation of p38 and p53 and inhibiting the activation of ERK. Moreover, uPA and MMP-2/MMP-9, among the most important metastatic regulatory proteins, were also found to be significantly alerted after the treatment. Furthermore, we also found that tumor growth in nude mice was significantly inhibited by iron complex Fe2 through the induction of apoptosis without clear systematic toxicity, as indicated by histological analysis. Taken together, this study provides evidence for the further development of metal-based anticancer agents and chemosensitizers of TRAIL for the treatment of human glioblastoma cancer cells.

Selenadiazole Derivatives Inhibit Angiogenesis-Mediated Human Breast Tumor Growth by Suppressing the VEGFR2-Mediated ERK and AKT Signaling Pathways.

Selenadiazole derivatives (SeDs) have been found to show promise in chemo-/radiotherapy applications by activating various downstream signaling pathways. However, the functional role of SeDs on angiogenesis, which is pivotal for tumor progression and metastasis, has not yet been elucidated. In the present study, we have examined the antiangiogenic activities of SeDs and elucidated their underlying mechanisms. The results showed that the as-synthesized SeDs not only enhanced their anticancer activities against several human cancer cells but also showed more potent inhibition on human umbilical vein endothelial cells (HUVECs). The in vitro results suggested that SeDs, especially 1 a, dose-dependently inhibited the vascular endothelial growth factor (VEGF)-induced cell migration, invasion, and capillary-like structure formation of HUVECs. Compound 1 a also significantly suppressed VEGF-induced angiogenesis in a Matrigel plug assay as part of a C57/BL6 mice assay by means of down regulation of VEGF. Furthermore, we found that 1 a significantly inhibited MCF-7 human breast tumor growth in nude mice without severe systematic cytotoxicity. Compound 1 a was more effective in inhibiting cell proliferation and induced a much more pronounced apoptosis effect in endothelial cells than MCF-7 cells, which implies that endothelial cells might be the primary target of 1 a. Further mechanistic studies on tumor growth inhibition effects and neovessel formation suppression demonstrated that 1 a inhibited cell viability of MCF-7 and HUVECs by induction of cell apoptosis, accompanied by poly(adenosine diphosphate ribose)polymerase (PARP) cleavage and caspase activation. Additionally, the 1 a-induced antiangiogenesis effect was achieved by abolishing the VEGF-VEGFR2-ERK/AKT (ERK=extracellular signal-regulated kinases; AKT=protein kinease B) signal axis and enhanced the apoptosis effect by triggering reactive oxygen species (ROS)-mediated DNA damage. Taken together, these results clearly demonstrate the antiangiogenic potency of SeDs and the underlying molecular mechanisms.

Enhancement of Antiangiogenic Efficacy of Iron(II) Complex by Selenium Substitution.

Antiangiogenesis therapy is a proven strategy for the treatment of cancers. Herein, we demonstrate that iron(II) complexes containing 1,10-phenanthroline(phen) derivatives were capable of suppressing angiogenesis in vitro in a dose-dependent manner. Interestingly, the introduction of selenium into an iron(II) complex ((Fe(phenSe)3 (ClO4 )2 (phenSe=2-selenoimidazole[4,5-f]1,10-phenanthroline)) could enhance its antiangiogenic efficacy. Mechanistic studies demonstrated that the complex potently induced endothelial cell apoptosis as evidenced by activation of caspases and PARP cleavage. The iron(II) complex activated p53-mediated mitochondrial dysfunction as can be seen by the upregulation in the expression of p53 and proapoptotic Bcl-2 family proteins, and downregulation in the expression of Bcl-2 family proteins. Additionally, the complex inhibited VEGF expression and gave rise to dephosphorylated AKT, which suppressed the transmission of the mitogenic signaling pathway. Taken together, this study could provide a strategy for the rational design of high-efficacy antivascular agents.

RGD peptide-conjugated selenium nanoparticles: antiangiogenesis by suppressing VEGF-VEGFR2-ERK/AKT pathway.

Angiogenesis is essential for tumorigenesis, progression and metastasis. Herein we described the synthesis of RGD peptide-decorated and doxorubicin-loaded selenium nanoparticles (RGD-NPs) targeting tumor vasculature to enhance the cellular uptake and antiangiogenic activities in vitro and in vivo. After internalization by receptor-mediated endocytosis, this nanosystem disassembled under acidic condition with the presence of lysozymes and cell lysate, leading to bioresponsive triggered drug release. Mechanistic investigation revealed that RGD-NPs inhibited angiogenesis through induction of apoptosis and cell cycle arrest in human umbilical vein endothelial cells (HUVECs) via suppression of VEGF-VEGFR2-ERK/AKT signaling axis by triggering ROS-mediated DNA damage. Additionally, RGD-NPs can inhibit MCF-7 tumor growth and angiogenesis in nude mice via down-regulation of VEGF-VEGFR2, effectively reduce the toxicity and prolong the blood circulation in vivo. Our results suggest that the strategy to use RGD-peptide functionalized SeNPs as carriers of anticancer drugs is an efficient way to achieve cancer-targeted antiangiogenesis synergism.