Functionalized Selenium Nanoparticles Research Articles

Plant Extracts for Production of Functionalized Selenium Nanoparticles.

In recent years, selenium nanoparticles (SeNPs) have attracted expanding consideration, particularly in the nanotechnology field. This element participates in important biological processes, such as antioxidant defense, immune function, and thyroid hormone regulation, protecting cells from oxidative damage. Selenium in the form of nanoscale particles has drawn attention for its biocompatibility, bioavailability, and low toxicity; thus, it has found several biomedical applications in diagnosis, treatment, and monitoring. Green methods for SeNP synthesis using plant extracts are considered to be single-step, inexpensive, and eco-friendly processes. Besides acting as natural reductants, compounds from plant extracts can also serve as natural capping agents, stabilizing the size of nanoparticles and contributing to the enhanced biological properties of SeNPs. This brief overview presents the recent developments in this area, focusing on the synthesis conditions and the characteristics of the obtained SeNPs.

Intracellular Fate of Sub-Toxic Concentration of Functionalized Selenium Nanoparticles in Aggressive Prostate Cancer Cells

Selenium 0 (Se0) is a powerful anti-proliferative agent in cancer research. We investigated the impact of sub-toxic concentrations of Se0 functionalized nanoparticles (SeNPs) on prostate cancer PC-3 cells and determined their intracellular localization and fate. An in-depth characterization of functionalized selenium nanoparticles composition is proposed to certify that no chemical bias relative to synthesis issues might have impacted the study. Selenium is an extremely diluted element in the biological environment and therefore requires high-performance techniques with a very low detection limit and high spatial resolution for intracellular imaging. This was explored with state-of-the-art techniques, but also with cryopreparation to preserve the chemical and structural integrity of the cells for spatially resolved and speciation techniques. Monodisperse solutions of SeNPs capped with bovine serum albumin (BSA) were shown to slow down the migration capacity of aggressive prostate cancer cells compared to polydisperse solutions of SeNPs capped with chitosan. BSA coating could prevent interactions between the reactive surface of the nanoparticles and the plasma membrane, mitigating the generation of reactive oxygen species. The intracellular localization showed interaction with mitochondria and also a localization in the lysosome-related organelle. The SeNPs-BSA localization in mitochondria constitute a possible explanation for our result showing a very significant dampening of the PC-3 cell proliferation capabilities. The purpose of the use of sublethal compound concentrations was to limit adverse effects resulting from high cell death to best evaluate some cellular changes and the fate of these SeNPs on PC-3. Our findings provide new insight to further study the various mechanisms of cytotoxicity of SeNPs.

Functionalized selenium nanoparticles ameliorated acetaminophen-induced hepatotoxicity through synergistically triggering PKCδ/Nrf2 signaling pathway and inhibiting CYP 2E1

Selenium nanoparticles (SeNPs) have been demonstrated potential for use in diseases associated with oxidative stress. Functionalized SeNPs with lower toxicity and higher biocompatibility could bring better therapeutic activity and clinical application value. Herein, this work was conducted to investigate the protective effect of Pleurotus tuber-regium polysaccharide-protein complex funtionnalized SeNPs (PTR-SeNPs) against acetaminophen (APAP)-induced oxidative injure in HepG2 cells and C57BL/6J mouse liver. Further elucidation of the underlying molecular mechanism, in particular their modulation of Nrf2 signaling pathway was also performed. The results showed that PTR-SeNPs could significantly ameliorate APAP-induced oxidative injury as evidenced by a range of biochemical analysis, histopathological examination and immunoblotting study. PTR-SeNPs could hosphorylate and activate PKCδ, depress Keap1, and increase nuclear accumulation of Nrf2, resulting in upregulation of GCLC, GCLM, HO-1 and NQO-1 expression. Besides, PTR-SeNPs suppressed the biotransformation of APAP to generate intracellular ROS through CYP 2E1 inhibition, restoring the mitochondrial morphology. Furthermore, the protective effect of PTR-SeNPs against APAP induced hepatotoxicity was weakened as Nrf2 was depleted in vivo, indicating the pivotal role of Nrf2 signaling pathway in PTR-SeNPs mediated hepatoprotective efficacy. Being a potential hepatic protectant, PTR-SeNPs could serve as a new source of selenium supplement for health-promoting and biomedical applications.

Inhibition of H2O2-induced apoptosis of GC2-spg cells by functionalized selenium nanoparticles with lentinan through ROS-mediated ERK/p53 signaling pathways

A H2O2-induced oxidative stress injury cell model was established to investigate the antioxidant effect of nano-selenium on mouse spermatocyte lines and the regulation mechanism of the expression level and activity of selenium-containing antioxidant enzymes induced by oxidative stress. A safe and effective nano-drug system of functionalized selenium-containing nanoparticles (SeNPs) was developed with lentinan (LNT) (SeNPs@LNT). Mice spermatocyte line GC2-spg cells were treated with SeNPs@LNT (1, 2, 4, 8, 16, 32 μM) for 24–72 h to evaluate the cytotoxicity of selenium. GC2-spg cells were randomly divided into the following groups: control, hydrogen peroxide (H2O2), SeNPs@LNT, and H2O2+SeNPs@LNT groups. H2O2+SeNPs@LNT group was pretreated with SeNPs@LNT 4 μM for 12 h, followed by H2O2 600 μM for 8 h. The cell viability decreased in the H2O2 group and increased significantly in the SeNPs@LNT group. Compared with the H2O2 group, the SeNPs@LNT+H2O2 group exhibited obvious red fluorescence, indicating a higher level of mitochondrial membrane potential. The content of intracellular reactive oxygen species (ROS) in the SeNPs@LNT group reduced significantly, and the intensity of green fluorescence in the SeNPs@LNT+H2O2 group decreased significantly compared with the H2O2 group, indicating the inhibitory effect of SeNPs@LNT on the generation of ROS-induced oxidative stress. The activity of GPx and SOD increased significantly in the SeNPs@LNT group. The expression of p53 decreased significantly under the intervention of nano-selenium, and GPx1 expression increased. In the oxidative stress group, the expressions of DNA damage-related proteins and apoptosis-related proteins were higher than those in other groups. Thus, SeNPs@LNT can promote GC2-spg cell proliferation, improve GPx and SOD activities, remove intracellular ROS, and reduce mitochondrial damage and functional abnormalities caused by oxidative stress by regulating the ERK and p53 protein levels. SeNPs@LNT has good biological activity and antioxidant effect, which can be used to protect the male reproductive system from oxidative stress.

Inhibition of H2O2-induced TM3 cell apoptosis by oxidative stress by lentinan functionalized selenium nanoparticles through JAK2/STAT-3 and P53 pathways

Inhibition of H2O2-induced TM3 cell apoptosis by oxidative stress by lentinan functionalized selenium nanoparticles through JAK2/STAT-3 and P53 pathways

Synthesis, characterization, and anticancer activity of protamine sulfate stabilized selenium nanoparticles

Selenium nanoparticles (SeNPs) have attracted much recent interest as nutraceuticals, while they face great challenges, such as poor stability and low cellular uptake efficiency. This study introduced a facile approach to synthesizing protamine sulfate (PS) functionalized selenium nanoparticles (PS-SeNPs) by using PS as a surface decorator. The monodisperse spherical PS-SeNPs with a particle size of 130 nm and a ζ-potential of +31 mV were ligated with PS through Se-N, Se-O bonds, and physical adsorption, which exhibits excellent physical stability against pH, temperature, and storage time. The positive surface charge of PS-SeNPs contributed to the enhancement of cellular uptake efficiency by endocytosis, which was 3-times higher than bare SeNPs. Compared to SeNPs (IC50 = 17.675 μg/mL), PS-SeNPs could dramatically inhibit the proliferation of HepG2 cells with an IC50 value of 5.507 μg/mL, as reflected by the induction of apoptosis, S phase arresting, overproduction of intracellular ROS, and depolarization of mitochondria membrane. Overall, these results demonstrated the great potential of PS-SeNPs that can be applied as a functional ingredient in foods and nutraceuticals.

Use of agricultural production waste in relation to bio nano technology for the synthesis of functionalized selenium nanoparticles

The application of nanotechnological innovations to increase the effectiveness of the bioflavonoid quercetin is considered. The ability to functionalize with specific ligands that target specific organs or cells is very important because it is possible to increase the concentration of quercetin at the desired target level while reducing side effects. Quercetin, as a flavonoid antioxidant, is widely used to reduce oxidative stress and activate important signalling pathways in cells. However, poor solubility in water, intensive first-pass metabolism limits its use. A strategy for the development of nanocomposites is presented, which involves combining quercetin obtained from agricultural waste with selenium nanoparticles. In vitro results demonstrated that quercetin-nanoselenium has high water solubility compared to individual flavonoids. It has been proven that quercetin-nano-selenium nanoparticles are capable of reducing 1,1-dipheny l-2-picrylhydrazyl (DPPH) radicals and are characterized by high antioxidant activity. The ability to functionalize nanoparticles with specific ligands that target the modulation of specific signaling pathways (Keap1/ Nrf2/ARE, Nf-kB, mTOR) in individual cells is very important, as it allows increasing the concentration of quercetin to the desired level while reducing side effects. Considering the beneficial effects of quercetin, a strategy has been developed that involves the use of selenium nanoparticles to deliver quercetin in a specific and controlled manner. Research in this direction is promising, as it will contribute to clarifying the expediency of using such nanosystems, which have not yet been widely used. The use of onion waste and its extracts in biotechnology, biomedicine, pharmaceuticals and the agro-industrial sector can be an optimal solution for reducing environmental damage. In addition, it will provide an economically determined alternative for the production of feed additives for animals and poultry. Compounds of quercetin with nanoselenium should take a worthy place in clinical medical practice, biology and agriculture. The beneficial effects of quercetin can be further enhanced with the help of nanotechnology, which will contribute to the effective use of this compound with such great biological potential. Key words: nanobiotechnologies, waste, onion peel, 1,1-dipheny l- 2-picrylhydrazyl, antiradical activity.

Construction of Polygonatum sibiricum Polysaccharide Functionalized Selenium Nanoparticles for the Enhancement of Stability and Antioxidant Activity.

Although selenium nanoparticles (SeNPs) have attracted great attention due to their potential antioxidant activity and low toxicity, the application of SeNPs is still restricted by their poor stability. A combination of polysaccharides and SeNPs is an effective strategy to overcome the limitations. In this study, Polygonatum sibiricum polysaccharide (PSP) was used as a stabilizer to fabricate SeNPs under a simple redox system. Dynamic light scattering, transmission electron microscopy, energy dispersive X-ray, ultraviolet-visible spectroscopy, Fourier transform infrared, and X-ray photoelectron spectrometer were applied to characterize the synthesized PSP-SeNPs. The stability and the antioxidant activity of PSP-SeNPs were also investigated. The results revealed that the zero-valent and well-dispersed spherical PSP-SeNPs with an average size of 105 nm and a negative ζ-potential of −34.9 mV were successfully synthesized using 0.1 mg/mL PSP as a stabilizer. The prepared PSP-SeNPs were stable for 30 days at 4 °C. The decoration of the nanoparticle surface with PSP significantly improved the free radical scavenging ability of SeNPs. Compared to the H2O2-induced oxidative stress model group, the viability of PC-12 cells pretreated with 20 μg/mL PSP-SeNPs increased from 56% to 98%. Moreover, PSP-SeNPs exhibited a higher protective effect on the H2O2-induced oxidative damage on PC-12 cells and lower cytotoxicity than sodium selenite and SeNPs. In summary, these results suggest the great potential of PSP-SeNPs as a novel antioxidant agent in the food or nutraceuticals area.

Functionalized Selenium Nanoparticles Synergizes With Metformin to Treat Breast Cancer Cells Through Regulation of Selenoproteins.

Owing to high blood sugar level and chronic inflammation, diabetes tend to cause the overproduction of free radicals in body, which will damage tissue and cells, reduce autoimmunity, and greatly increase the incidence of tumors. Selenium nanoparticles (SeNPs) exhibit high antioxidant activity with anti-tumor ability. In addition, metformin is considered as a clinical drug commonly for the treatment of stage II diabetes. Therefore, in this study, different functionalized SeNPs combined with metformin were performed to detect the feasibility for cancer therapy. The combination of Tween 80 (TW80)-SeNPs and metformin was found to have a synergistic effect on MCF-7 cells. The mechanism of this synergistic effect involved in the induction of DNA damage by affecting the generation of reactive oxygen species through selenoproteins; the upregulation of DNA-damage-related proteins including p-ATM, p-ATR, and p38; the promotion of p21 expression; and the downregulation of cyclin-dependent kinases and cyclin-related proteins causing cell cycle arrest. Furthermore, the expression of AMPK was affected, which in turn to regulate the mitochondrial membrane potential to achieve the synergistic treatment effect.

Hepatocellular-Targeted mRNA Delivery Using Functionalized Selenium Nanoparticles In Vitro.

Selenium’s (Se) chemopreventative and therapeutic properties have attracted attention in nanomedicine. Se nanoparticles (SeNPs) retain these properties of Se while possessing lower toxicity and higher bioavailability, potentiating their use in gene delivery. This study aimed to formulate SeNPs for efficient binding and targeted delivery of FLuc-mRNA to hepatocellular carcinoma cells (HepG2) in vitro. The colorectal adenocarcinoma (Caco-2) and normal human embryonic kidney (HEK293) cells that do not have the asialoorosomucoid receptor (ASGPR) were utilized for comparison. SeNPs were functionalized with chitosan (CS), polyethylene glycol (PEG), and lactobionic acid (LA) for ASGPR targeting on HepG2 cells. Nanoparticles (NPs) and their mRNA-nanocomplexes were characterized by Fourier transform infra-red (FTIR) and UV-vis spectroscopy, transmission electron microscopy (TEM), and nanoparticle tracking analysis (NTA). Gel and fluorescence-based assays assessed the NP’s ability to bind and protect FLuc-mRNA. Cytotoxicity was determined using the -(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, while transgene expression was evaluated using the luciferase reporter gene assay. All NPs appeared spherical with sizes ranging 57.2–130.0 nm and zeta potentials 14.9–31.4 mV. NPs bound, compacted, and protected the mRNA from nuclease digestion and showed negligible cytotoxicity in vitro. Targeted gene expression was highest in the HepG2 cells using the LA targeted NPs. These NPs portend to be efficient nanocarriers of nucleic acids and warrant further investigation.

Tumor-targeted delivery of siRNA to silence Sox2 gene expression enhances therapeutic response in hepatocellular carcinoma

RNA interference (RNAi) is one of the most promising methods for the treatment of malignant tumors. However, developing an efficient biocompatible delivery vector for small interfering RNA (siRNA) remains a challenging issue. This study aimed to prepare a non-viral tumor-targeted carrier, named RGDfC-modified functionalized selenium nanoparticles (RGDfC-SeNPs). RGDfC-SeNPs were used to selectively deliver siSox2 to HepG2 liver cancer cells and tissues for the treatment of hepatocellular carcinoma (HCC). In the current study, RGDfC-SeNPs were successfully synthesized and characterized. It was shown that RGDfC-SeNPs could effectively load siSox2 to prepare an antitumor prodrug RGDfC-Se@siSox2. RGDfC-Se@siSox2 exhibited selective uptake in HepG2 liver cancer cells and LO2 normal liver cells, indicating RGDfC-SeNPs could effectively deliver siSox2 to HepG2 liver cancer cells. RGDfC-Se@siSox2 entered HepG2 cells via clathrin-mediated endocytosis by firstly encircling the cytoplasm and then releasing siSox2 in the lysosomes. RGDfC-Se@siSox2 could effectively silence Sox2 and inhibit the proliferation, migration and invasion of HepG2 cells. RGDfC-Se@siSox2 induced HepG2 cells apoptosis most likely via overproduction of reactive oxygen species and disruption of the mitochondrial membrane potentials. Most importantly, RGDfC-Se@siSox2 significantly inhibited the tumor growth in HepG2 tumor-bearing mice without obvious toxic side effects. These studies indicated that RGDfC-SeNPs may be an ideal gene carrier for delivering siSox2 to HepG2 cells and that RGDfC-Se@siSox2 may be a novel and highly specific gene-targeted prodrug therapy for HCC.

Folate-Targeted Transgenic Activity of Dendrimer Functionalized Selenium Nanoparticles In Vitro.

Current chemotherapeutic drugs, although effective, lack cell-specific targeting, instigate adverse side effects in healthy tissue, exhibit unfavourable bio-circulation and can generate drug-resistant cancers. The synergistic use of nanotechnology and gene therapy, using nanoparticles (NPs) for therapeutic gene delivery to cancer cells is hereby proposed. This includes the benefit of cell-specific targeting and exploitation of receptors overexpressed in specific cancer types. The aim of this study was to formulate dendrimer-functionalized selenium nanoparticles (PAMAM-SeNPs) containing the targeting moiety, folic acid (FA), for delivery of pCMV-Luc-DNA (pDNA) in vitro. These NPs and their gene-loaded nanocomplexes were physicochemically and morphologically characterized. Nucleic acid-binding, compaction and pDNA protection were assessed, followed by cell-based in vitro cytotoxicity, transgene expression and apoptotic assays. Nanocomplexes possessed favourable sizes (<150 nm) and ζ-potentials (>25 mV), crucial for cellular interaction, and protected the pDNA from degradation in an in vivo simulation. PAMAM-SeNP nanocomplexes exhibited higher cell viability (>85%) compared to selenium-free nanocomplexes (approximately 75%), confirming the important role of selenium in these nanocomplexes. FA-conjugated PAMAM-SeNPs displayed higher overall transgene expression (HeLa cells) compared to their non-targeting counterparts, suggesting enhanced receptor-mediated cellular uptake. Overall, our results bode well for the use of these nano-delivery vehicles in future in vivo studies.

Lentinan-functionalized Selenium Nanoparticles target Tumor Cell Mitochondria via TLR4/TRAF3/MFN1 pathway.

Rationale: Malignant ascites caused by cancer cells results in poor prognosis and short average survival time. No effective treatment is currently available for malignant ascites. In this study, the effects of lentinan (LNT)-functionalized selenium nanoparticles (Selene) on malignant ascites were evaluated. Furthermore, the mechanism of Selene targeting mitochondria of tumor cells were also investigated.Methods: Selene were synthesized and characterized by TEM, AFM and particle size analysis. The OVCAR-3 and EAC cells induced ascites models were used to evaluate the effects of Selene on malignant ascites. Proteomic analysis, immunofluorescence, TEM and ICP-MS were used to determine the location of Selene in tumor cells. Mitochondrial membrane potential, ROS, ATP content, and caspase-1/3 activity were detected to evaluate the effect of Selene on mitochondrial function and cell apoptosis. Immunofluorescence, Co-IP, pull-down, duolink, Western blot, and FPLC were used to investigate the pathway of Selene targeting mitochondria.Results: Selene could effectively inhibit ascites induced by OVCAR-3 and EAC cells. Selene was mainly located in the mitochondria of tumor cells and induced apoptosis of tumor cells. The LNT in Selene was involved in caveolae-mediated endocytosis through the interaction between toll-like receptor-4 (TLR4) and caveolin 1 (CAV1). Furthermore, the Selene in the endocytic vesicles could enter the mitochondria via the mitochondrial membrane fusion pathway, which was mediated by TLR4/TNF receptor associated factor 3 (TRAF3)/mitofusin-1 (MFN1) protein complex.Conclusion: Selene is a candidate anticancer drug for the treatment of malignant ascites. And TLR4/TRAF3/MFN1 may be a specific nano-drug delivery pathway that could target the mitochondria.

Functionalized selenium nanoparticles for targeted siRNA delivery silence Derlin1 and promote antitumor efficacy against cervical cancer

Small interfering RNA (siRNA) exhibits great potential as a novel therapeutic option due to its highly sequence-specific ability to silence genes. However, efficient and safe delivery carriers are required for developing novel therapeutic paradigms. Thus, the successful development of efficient delivery platforms for siRNA is a crucial issue for the development of siRNA-based drugs in cancer treatments. In this study, biocompatible selenium nanoparticles (SeNPs) were loaded with RGDfC peptide to fabricate tumor-targeting gene delivery vehicle RGDfC-SeNPs. Subsequently, RGDfC-SeNPs were loaded with Derlin1-siRNA to fabricate RGDfC-Se@siRNA, which are functionalized selenium nanoparticles. RGDfC-Se@siRNA showed greater uptake in HeLa cervical cancer cells in comparison with that in human umbilical vein endothelial cells (HUVECs), verifying the RGDfC-mediated specific uptake of RGDfC-Se@siRNA. RGDfC-Se@siRNA was capable of entering HeLa cells via clathrin-associated endocytosis, and showed faster siRNA release in a cancer cell microenvironment in comparison with a normal physiological environment. qPCR and western blotting assays both indicated that RGDfC-Se@siRNA exhibited an obvious gene silencing efficacy in HeLa cells. RGDfC-Se@siRNA suppressed the invasion, migration and the proliferation of HeLa cells, and triggered HeLa cell apoptosis. Moreover, RGDfC-Se@siRNA induced the disruption of mitochondrial membrane potentials. Meanwhile, RGDfC-Se@siRNA enhanced the generation of reactive oxygen species (ROS) in HeLa cell, suggesting that mitochondrial dysfunction mediated by ROS might play a significant role in RGDfC-Se@siRNA-induced apoptosis. Interestingly, RGDfC-SeNPs@siRNA exhibited significant antitumor activity in a HeLa tumor-bearing mouse model. Additionally, RGDfC-SeNPs@siRNA is nontoxic to main organ of mouse. The above results indicate that RGDfC-Se@siRNA provides a promising potential for cervical cancer therapy.

Utilizing corona on functionalized selenium nanoparticles for loading and release of doxorubicin payload

Incorporation of nanoparticles in serum containing-media leads to spontaneous adsorption of proteins on the nanoparticle surface thus forming “protein corona”. The current study focuses on the variation in corona formation across differently functionalized (CTAB, SDS and Brij-58) SeNPs surfaces and the application of these coronated-SeNPs as reservoirs for holding positively charged doxorubicin (dox). Protein quantification and densitometry study reveal that cationic SeNPs (CTAB-SeNPs) promotes maximum corona formation, and also has a higher affinity towards predominantly negatively charged serum albumin. Further, protein coronation had a significant impact on the mean hydrodynamic diameter of the functionalized SeNPs. Parameters such as surface functionalization, total adsorbed protein and bound albumin content determine the loading capacity and release of dox payload. Protein densitometry reveals, that CTAB-SeNPs has the highest amount of bound albumin which in turn aided in enhanced loading of dox on the cationic NPs. The coronated-nanocarriers were further subjected to different pH-trigger, wherein all the coronated SeNPs had an enhanced dox release at pH- 4.6. The study also highlights that protein corona helps in impeding the burst release of dox from the conjugated system. Additionally, payload leakage study suggests, that bound corona proteins help in retaining dox and prevents significant desorption of the therapeutic molecule over time. However, the presence of positively charged dox disrupts the stability of the bound corona proteins making them prone to leakage. Finally, the cellular toxicity of the functionalized NPs were assessed, wherein dox-loaded protein coronated SeNPs induced significant cell death. The feasibility of employing protein-coronated-SeNPs as a new mode of drug delivery has been highlighted in this study.

Hyaluronic acid-modified selenium nanoparticles for enhancing the therapeutic efficacy of paclitaxel in lung cancer therapy

Targeted delivery of chemotherapeutics by functionalized nanoparticles exhibits a wonderful prospect for cancer treatment. In this paper, selenium nanoparticles (SeNPs) was linked with hyaluronic acid (HA) to prepare tumor-targeted delivery vehicle HA-SeNPs, and HA-SeNPs was loaded with paclitaxel (PTX) to fabricate functionalized selenium nanoparticles HA-Se@PTX. HA-Se@PTX showed greater uptake in A549 cells in comparison with that in HUVEC, verifying HA-mediated specific uptake of HA-Se@PTX. HA-Se@PTX was capable of entering A549 cells via clathrin-associated endocytosis and showed faster drug release in cancer cell microenvironment in comparison with normal physiological environment. HA-Se@PTX could obviously inhibit the proliferation, migration and invasion of A549 cells and trigger A549 cells apoptosis. Moreover, active targeting functionalized selenium nanoparticles HA-Se@PTX showed greater in vivo antitumor activity compared with free PTX or passive targeting delivery system Se@PTX. In addition, HA-Se@PTX exhibited negligible toxicity on the major organs of mice. In a word, HA-Se@PTX may develop into a valuable nanoscale antitumor drug agent for lung cancer treatment.

Doxorubicin-loaded functionalized selenium nanoparticles for enhanced antitumor efficacy in cervical carcinoma therapy.

Development of novel tumor-targeted drug vehicles for cancer therapy is very important and has become one of major topics for designing nanoscale chemotherapeutics delivery systems. In the present study, selenium nanoparticles (SeNPs) was decorated with hyaluronic acid (HA) to prepare HA-SeNPs nanoparticles which were used to load doxorubicin (DOX) to fabricate tumor-targeted functionalized selenium nanoparticles HA-Se@DOX. In vitro and in vivo antitumor activities of HA-Se@DOX in human cervical carcinoma treatment were investigated. HA-Se@DOX showed selective cellular uptakes between cervical cancer HeLa cells and human umbilical vein endothelial cells (HUVEC). In vitro release result indicated that DOX was released from HA-SeNPs faster in acidic environment in comparison with normal physiological environment and 76.9% DOX was released in pH 5.4 during initial 30 h. HA-Se@DOX showed high activity to inhibit HeLa cell proliferation and triggered HeLa cell apoptosis via activating Bcl-2 signaling pathway. In vivo antitumor study showed that HA-Se@DOX inhibited tumor growth through suppressing cancer cells proliferation and inducing cancer cells apoptosis. Interestingly, HA-Se@DOX exhibited stronger anticancer activity than free DOX and Se@DOX in vitro and in vivo. Additionally, HA-Se@DOX did not cause damage to major organs at the used dose. HA-Se@DOX is a promising antitumor agent for human cervical carcinoma treatment and this research provides a novel therapeutic strategy for cancer therapy.

Designing multifunctionalized selenium nanoparticles to reverse oxidative stress-induced spinal cord injury by attenuating ROS overproduction and mitochondria dysfunction.

Spinal cord injury (SCI) remains a challenging clinical problem worldwide, due to the lack of effective drugs for precise treatment. Among the complex pathophysiological events following SCI, reactive oxygen species (ROS) overproduction plays a particularly significant role. As therapeutic agents for neurological diseases, tetramethylpyrazine (TMP) and monosialotetrahexosylganglioside (GM1) have been widely used in the clinical treatment of SCI. Our previous studies have reported that functionalized selenium nanoparticles (SeNPs) exhibit excellent antioxidant activity against oxidative stress-related diseases. Therefore, in this study, novel multifunctionalized SeNPs decorated with polysaccharide-protein complex (PTW)/PG-6 peptide and loaded with TMP/GM1 were rationally designed and synthesized, which exhibited a satisfactory size distribution and superior stability. Furthermore, the protective effects of SeNPs@GM1/TMP on PC12 cells against tert-butyl hydroperoxide (t-BOOH)-induced cytotoxicity and the underlying mechanisms were also explored. Flow cytometric analysis indicated that SeNPs@GM1/TMP showed strongly protective effects against t-BOOH-induced G2/M phase arrest and apoptosis. Moreover, we found that SeNPs@GM1/TMP could attenuate ROS overproduction to prevent mitochondria dysfunction via inhibiting the activation of p53 and MAPK pathways. Effects of SeNPs@GM1/TMP on functional recovery after SCI were evaluated by the Basso-Beattie-Bresnahan (BBB) locomotion scale, inclined plane test, and footprint analysis. The results of hematoxylin-eosin staining and Nissl staining also showed that SeNPs@GM1/TMP provided a neuroprotective effect in SCI rats. This finding suggests that SeNPs@GM1/TMP could be further developed as a promising nanomedicine for efficient SCI treatment.

Multifunctional selenium nanoparticles with Galangin-induced HepG2 cell apoptosis through p38 and AKT signalling pathway.

The morbidity and mortality of hepatocellular carcinoma, the most common cancer, are increasing continuously worldwide. Galangin (Ga) has been demonstrated to possess anti-cancer effect, but the efficacy of Ga was limited by its low permeability and poor solubility. To develop aqueous formulation and improve the anti-cancer activity of Ga, surface decoration of functionalized selenium nanoparticles with Ga (Se@Ga) was synthesized in the present study. The aim of this study was to evaluate the anti-cancer effect of Se@Ga and the mechanism on HepG2 cells. Se@Ga-induced HepG2 cell apoptosis was confirmed by depletion of mitochondrial membrane potential, translocation of phosphatidylserine and caspase-3 activation. Furthermore, Se@Ga enhanced the anti-cancer activity of HepG2 cells through ROS-mediated AKT and p38 signalling pathways. In summary, these results suggest that Se@Ga might be potential candidate chemotherapy for cancer.

Functionalized selenium nanoparticles for targeted delivery of doxorubicin to improve non-small-cell lung cancer therapy.

BackgroundSelenium nanoparticles (SeNPs) loaded with chemotherapeutic drugs provided a novel perspective for cancer therapy.Materials and methodsHere, SeNPs were modified with cyclic peptide (Arg–Gly–Asp–d-Phe–Cys [RGDfC]) to fabricate tumor-targeting delivery carrier RGDfC-SeNPs and, then, doxorubicin (DOX) was loaded to the surface of RGDfC-SeNPs for improving the antitumor efficacy of DOX in non-small-cell lung carcinoma therapy.ResultsThe chemical structure characterization of RGDfC-Se@DOX showed that DOX was successfully loaded to the surface of RGDfC-SeNPs to prepare functionalized antitumor drug delivery system RGDfC-Se@DOX. RGDfC-Se@DOX exhibited effective cellular uptake in A549 cells and entered A549 cells mainly by clathrin-mediated endocytosis pathway. Compared to free DOX or Se@DOX at the equivalent dose of DOX, RGDfC-Se@DOX showed greater activity to inhibit A549 cells’ proliferation and migration/invasion and induce A549 cells’ apoptosis. More importantly, compared with passive targeting delivery system Se@DOX, active targeting delivery system RGDfC-Se@DOX exhibited more significant antitumor efficacy in vivo.ConclusionTaken together, RGDfC-Se@DOX may be a novel promising drug candidate for the lung carcinoma therapy.