Apoptotic efficacy and antiproliferative potential of silver nanoparticles synthesised from aqueous extract of sumac (Rhus coriaria L.)

Currently, nanotechnology and nanoparticles (NPs) are recognised due to their extensive applications in medicine and the treatment of certain diseases, including cancer. Silver NPs (AgNPs) synthesised by environmentally friendly method exhibit a high medical potential. This study was conducted to determine the cytotoxic and apoptotic effects of AgNPs synthesised from sumac (Anacardiaceae family) fruit aqueous extract (AgSu/NPs) on human breast cancer cells (MCF‐7). The anti‐proliferative effect of AgSu/NPs was determined by MTT assay. The apoptotic properties of AgSu/NPs were assessed by morphological analysis and acridine orange/propidium iodide (AO/PI) and DAPI staining. The mechanism of apoptosis induction in treated cells was investigated using molecular analysis. Overall results of morphological examination and cytotoxic assay revealed that AgSu/NPs exert a concentration‐dependent inhibitory effect on the viability of MCF‐7 cells (IC50 of ∼10 µmol/48 h). AO/PI staining confirmed the occurrence of apoptosis in cells treated with AgSu/NPs. In addition, molecular analysis demonstrated that the apoptosis in MCF‐7 cells exposed to AgSu/NPs was induced via up‐regulation of Bax and down‐regulation of Bcl‐2. These findings suggested the potential use of AgSu/NP as cytotoxic and pro‐apoptotic efficacy and its possible application in modern medicine for treating certain disorders, such as cancer.Inspec keywords: nanoparticles, silver, nanomedicine, biomedical materials, toxicology, cancer, molecular biophysics, proteins, biochemistry, cellular biophysics, nanofabricationOther keywords: Ag, Bcl‐2 down‐regulation, Bax up‐regulation, MCF‐7 cell viability, concentration‐dependent inhibitory effect, cytotoxic assay, molecular analysis, DAPI staining, acridine orange‐propidium iodide staining, morphological analysis, MTT assay, human breast cancer cells, sumac fruit aqueous extract, Anacardiaceae family, cytotoxic effects, drug delivery function, diseases, Rhus coriaria L, silver nanoparticles, antiproliferative potential, apoptotic efficacy     

Mechanistic Differences in Cell Death Responses to Metal‐Based Engineered Nanomaterials in Kupffer Cells and Hepatocytes

The mononuclear phagocyte system in the liver is a frequent target for nanoparticles (NPs). A toxicological profiling of metal‐based NPs is performed in Kupffer cell (KC) and hepatocyte cell lines. Sixteen NPs are provided by the Nanomaterial Health Implications Research Consortium of the National Institute of Environmental Health Sciences to study the toxicological effects in KUP5 (KC) and Hepa 1–6 cells. Five NPs (Ag, CuO, ZnO, SiO₂, and V₂O₅) exhibit cytotoxicity in both cell types, while SiO₂ and V₂O₅ induce IL‐1β production in KC. Ag, CuO, and ZnO induced caspase 3 generated apoptosis in both cell types is accompanied by ion shedding and generation of mitochondrial reactive oxygen species (ROS) in both cell types. However, the cell death response to SiO₂ in KC differs by inducing pyroptosis as a result of potassium efflux, caspase 1 activation, NLRP3 inflammasome assembly, IL‐1β release, and cleavage of gasdermin‐D. This releases pore‐performing peptide fragments responsible for pyroptotic cell swelling. Interestingly, although V₂O₅ induces IL‐1β release and delays caspase 1 activation by vanadium ion interference in membrane Na⁺/K⁺ adenosine triphosphate (ATP)ase activity, the major cell death mechanism in KC (and Hepa 1–6) is caspase 3 mediated apoptosis. These findings improve the understanding of the mechanisms of metal‐based engineered nanomaterial (ENM) toxicity in liver cells toward comprehensive safety evaluation.     

Ultrasmall Ag+-rich nanoclusters as highly efficient nanoreservoirs for bacterial killing

Metallic silver （Ag） and its ability to combat infection have been known since ancient history. In the wake of nanotechnology advancement, silver＇s efficacy to fight broad spectrum bacterial infections is further improved in the form of Ag nanoparticles （NPs）. Recent studies have ascribed the broad spectrum antimicrobial properties of Ag NPs to dissociation of Ag＊ ions from the NPs, which may not be entirely applicable when the size of Ag NPs decreases to the sub-2 nm range [denoted Ag nanoclusters （NCs）]. In this paper we report that ultrasmall glutathione （GSH）-protected Ag^＋-rich NCs （Ag^＋-R NCs for short, with a predominance of Ag＋ species in the NCs） have much higher antimicrobial activities towards both gram-negative and gram-positive bacteria than the reference NC, GSH-Ag^＋-R NCs. They have the same size and surface ligand, but with different oxidation states of the core silver. This interesting finding suggests that the undissociated Ag^＋-R NCs armed with abundant Ag^＋ ions on the surface are highly active in bacterial killing, which was not observed in the system of their larger counterpart, Ag NPs.     

Implications of silver nanoparticle induced cell apoptosis for in vitro gene therapy

The impact of manufactured nanomaterials on human health and the environment is a major concern for commercial use of nanotechnology based products. A judicious choice of selective usage, lower nanomaterial concentration and use in combination with conventional therapeutic materials may provide the best solution. For example, silver nanoparticles (Ag NPs) are known to be bactericidal and also cytotoxic to mammalian cells. Herein, we investigate the molecular mechanism of Ag NP mediated cytotoxicity in both cancer and non-cancer cells and find that optimum particle concentration leads to programmed cell death in vitro. Also, the benefit of the cytotoxic effects of Ag NPs was tested for therapeutic use in conjunction with conventional gene therapy. The synergistic effect of Ag NPs on the uracil phosphoribosyltransferase expression system sensitized the cells more towards treatment with the drug 5-fluorouracil. Induction of the apoptotic pathway makes Ag NPs a representative of a new chemosensitization strategy for future application in gene therapy.     

Cytotoxicity of biologically synthesised bismuth nanoparticles against HT‐29 cell line

This study was purposed to examine the cytotoxicity and functions of biologically synthesised bismuth nanoparticles (Bi NPs) produced by Delftia sp. SFG on human colon adenocarcinoma cell line of HT‐29. The structural properties of Bi NPs were investigated using transmission electron microscopy, energy dispersive X‐ray, and X‐ray diffraction techniques. The cytotoxic effects of Bi NPs were analysed using flow cytometry cell apoptosis while western blot analyses were applied to analyse the cleaved caspase‐3 expression. Oxidative stress (OS) damage was determined using the measurement of the glutathione (GSH) and malondialdehyde (MDA) levels and antioxidant activity of superoxide dismutase (SOD) and catalase (CAT) levels. The half maximal inhibitory concentration (IC₅₀) value of Bi NPs was measured to be 28.7 ± 1.4 µg/ml on HT‐29 cell line. The viability of HT‐29 represented a concentration‐dependent pattern (5–80 µg/ml). The mode of Bi NPs induced apoptosis was found to be mainly related to late apoptosis or necrosis at IC₅₀ concentration, without the effect on caspase‐3 activities. Furthermore, Bi NPs reduced the GSH and increased the MDA levels and decreased the SOD and CAT activities. Taken together, biogenic Bi NPs induced cytotoxicity on HT‐29 cell line through the activation of late apoptosis independent of caspase pathway and may enhance the OS biomarkers.Inspec keywords: bismuth, nanoparticles, cellular biophysics, toxicology, nanomedicine, cancer, transmission electron microscopy, X‐ray chemical analysis, X‐ray diffraction, enzymes, biochemistryOther keywords: cytotoxicity, biologically synthesised bismuth nanoparticles, HT‐29 cell line, Delftia sp. SFG, human colon adenocarcinoma cell line, structural properties, transmission electron microscopy, energy dispersive X‐ray techniques, X‐ray diffraction, cytotoxic effects, flow cytometry cell apoptosis, western blot analyses, cleaved caspase‐3 expression, oxidative stress damage, glutathione, malondialdehyde, antioxidant activity, superoxide dismutase, catalase level, half maximal inhibitory concentration, cell viability, concentration‐dependent pattern, apoptosis, MDA levels, caspase pathway, Bi     

Fabrication of chitosan/silver nanocomposites based on electrochemical methods for removing formaldehyde in air

We report here a new pathway to prepare chitosan (Ch)-capped silver nanoparticles (NPs) in aqueous solutions without addition of any stabilizer and reductant. First, 1 g L⁻¹ Ch was added in a 0.05 N AgNO₃ aqueous solution with pH 6.6. Then the solution was heated from room temperature to boiling at a heating rate of 6 °C min⁻¹ to prepare Ch/Ag nanocomposites (NCs). The particle size of prepared Ag NPs with main (1 1 1) face on Ch is ca. 10 nm. Encouragingly, the prepared Ch/Ag NCs are more active catalysts than Ch is for the decomposition of 2 ppm formaldehyde in a dark and sealed chamber. After testing for 24 h, the formaldehyde molecules were decomposed by ca. 96% and 65% via employing Ch/Ag NCs and Ch, respectively.     

The effect of the coupling agents KH550 and KH570 on the nanostructure and interfacial interaction of zinc oxide/chiral poly(amide–imide) nanocomposites containing l-leucine amino acid moieties

In this article, a series of optically active poly(amide–imide)/zinc oxide nanocomposites (PAI/ZnO NCs) with different ZnO contents were prepared by ultrasonic technique. For better dispersion of nanoparticles (NPs) in the PAI matrix, their surface was modified with two different silane coupling agents. Then, the effects of two linkers on dispersity of NPs, thermal stability and UV–Visible spectra of resulting NCs were investigated. The morphological structures, thermal, and UV properties of the prepared NCs with two different coupling agents were studied by X-ray diffraction, transmission electron micrograph, field emission scanning electron microscopy, thermogravimetric analysis, and UV–Visible analysis. These data demonstrated that the surface-modified ZnO NPs were homogeneously dispersed in the PAI matrix. However, in the case of KH570 the better dispersity is more pronounced.     

Hypnea musciformis‐mediated Ag/AgCl‐NPs inhibit pathogenic bacteria,HCT‐116 and MCF‐7 cells’ growth in vitro and Ehrlich ascites carcinoma cells in vivo in mice

In the present study, Ag/AgCl‐NPs were biosynthesised using Hypnea musciformis seaweed extract; NPs synthesis was confirmed by a change of colour and observation of a razor‐sharp peak at 424 nm by UV–visible spectroscopy. Synthesised nanoparticles were characterised by transmission electron microscopy, energy‐dispersive X‐ray spectroscopy, X‐ray powder diffraction and Fourier transform infrared spectroscopy. Bacterial cell growth inhibition proves that the Ag/AgCl‐NPs have strong antibacterial activity and cell morphological alteration was observed in treated bacterial cells using propidium iodide (PI). Ag/AgCl‐NPs inhibited Ehrlich ascites carcinoma (EAC) cells, colorectal cancer (HCT‐116) and breast cancer (MCF‐7) cell line in vitro with the IC₅₀ values of 40.45, 24.08 and 36.95 μg/ml, respectively. Initiation of apoptosis in HCT‐116 and MCF‐7 cells was confirmed using PI, FITC‐annexin V and Hoechst 33342 dye. No reaction oxygen species generation was observed in both treated and untreated cell lines. A significant increase of ATG‐5 gene expression indicates the possibility of autophagy cell death besides apoptosis in MCF‐7 cells. The initiation of apoptosis in EAC cells was confirmed by observing caspase‐3 protein expression. Ag/AgCl‐NPs inhibited 22.83% and 51% of the EAC cell growth in vivo in mice when administered 1.5 and 3.0 mg/kg/day (i.p.), respectively, for 5 consequent days.     

A new route to size and population control of silver clusters on colloidal TiO₂ nanocrystals

Formation of hybrid Ag-TiO(2) nanocrystals (NCs) in which Ag clusters are uniformly deposited on individual TiO(2) NC surface has been achieved by using hydrophobic surfactant-capped TiO(2) NCs in combination with a photodeposition technique. The population of Ag clusters on the individual TiO(2) NC surface can be controlled by the degree of hydrophobicity (e.g., the number of vacant sites) on the TiO(2) NC surface while their size may be altered simply by varying irradiation time. A reversible change in color of the resulting hybrid Ag-TiO(2) NCs is induced by alternating UV light and visible-light illumination; however, the size and population of Ag clusters on TiO(2) NCs are almost unchanged. Furthermore, these materials also exhibit much higher photocatalytic performance as compared to that of Ag supported on commercial TiO(2)-P25.     

Bovine serum albumin driven interfacial growth of selenium-gold/silver hybrid nanomaterials

Selenium (Se) nanorods (NRs) capped with BSA were used as precursor to synthesize Se-Au/Ag hybrid nanocrystals (NCs). Aqueous Au/Ag ions in the presence of fixed amount of purified dried Se NRs were reduced by ascorbic acid at 80 degrees C to generate respective nucleating centres which subsequently grew on the capped BSA hot spots. The hybrid NCs thus obtained were characterized by SEM, TEM, and EDS analysis while their synthesis was monitored simultaneously by UV-visible absorbance due to the surface plasmon resonance of Au and Ag nanoparticles (NPs). In both cases, a gradual decrease in the absorbance of Au/Ag NPs with respect to reaction time was observed which indicated a diminishing number density of such particles in colloidal aqueous phase. SEM and TEM analyses then explained the presence of Au NPs in self assembled ball shaped aggregates and their selective adsorption on Se NRs, whereas no self aggregated balls of Ag NPs were observed and they always grew on the Se NRs. The results were discussed on the basis of different routes followed by the Au and Ag nucleating centres to produced hybrid nanomaterials.     

Carbon Nanotubes Enabling Highly Efficient Cell Apoptosis by Low‐Intensity Nanosecond Electric Pulses via Perturbing Calcium Handling

Effective induction of targeted cancer cells apoptosis with minimum side effects has always been the primary objective for anti‐tumor therapy. In this study, carbon nanotubes (CNTs) are employed for their unique ability to target tumors and amplify the localized electric field due to the high aspect ratio. Highly efficient and cancer cell specific apoptosis is finally achieved by combining carbon nanotubes with low intensity nanosecond electric pulses (nsEPs). The underlying mechanism may be as follows: the electric field produced by nsEPs is amplified by CNTs, causing an enhanced plasma membrane permeabilization and Ca²⁺ influx, simultaneously triggering Ca²⁺ release from intracellular storages to cytoplasm in a direct/indirect manner. All the changes above lead to excessive mitochondrial Ca²⁺ uptake. Substructural damage and obvious mitochondria membrane potential depolarization are caused subsequently with the combined action of numerously reactive oxygen species production, ultimately initiating the apoptotic process through the translocation of cytochrome c to the cytoplasm and activating apoptotic markers including caspase‐9 and ‐3. Thus, the combination of nanosecond electric field with carbon nanotubes can actually promote HCT116 cell death via mitochondrial signaling pathway‐mediated cell apoptosis. These results may provide a new and highly efficient strategy for cancer therapy.     

Emergence of Gold‐Mesoporous Silica Hybrid Nanotheranostics: Dox‐Encoded,Folate Targeted Chemotherapy with Modulation of SERS Fingerprinting for Apoptosis Toward Tumor Eradication

Strategically fabricated theranostic nanocarrier delivery system is an unmet need in personalized medicine. Herein, this study reports a versatile folate receptor (FR) targeted nanoenvelope delivery system (TNEDS) fabricated with gold core silica shell followed by chitosan–folic acid conjugate surface functionalization by for precise loading of doxorubicin (Dox), resembled as Au@SiO₂‐Dox‐CS‐FA. TNEDS possesses up to 90% Dox loading efficiency and internalized through endocytosis pathway leading to pH and redox‐sensitive release kinetics. The superior FR‐targeted cytotoxicity is evaluated by the nanocarrier in comparison with US Food and Drug Administration (FDA)‐approved liposomal Dox conjugate, Lipodox. Moreover, TNEDS exhibits theranostic features through caspase‐mediated apoptosis and envisages high surface plasmon resonance enabling the nanoconstruct as a promising surface enhanced Raman scattering (SERS) nanotag. Minuscule changes in the biochemical components inside cells exerted by the TNEDS along with the Dox release are evaluated explicitly in a time‐dependent fashion using bimodal SERS/fluorescence nanoprobe. Finally, TNEDS displays superior antitumor response in FR‐positive ascites as well as solid tumor syngraft mouse models. Therefore, this futuristic TNEDS is expected to be a potential alternative as a clinically relevant theranostic nanomedicine to effectively combat neoplasia.     

Nonvolatile Memory Characteristics of NMOSFET With Ag Nanocrystals Synthesized via a Thermal Decomposition Process for Uniform Device Distribution

This paper presents nonvolatile memory characteristics using Ag nanocrystals (NCs) formed by a thermal decomposition and size-selective precipitation technique for Flash memory application. In the NC formation process, the size of NCs and the space NC-to-NC were precisely controlled by a size-selective precipitation technique and the length of the self-assembled monolayer surrounding the NCs, respectively. The size and density of the Ag NCs synthesized were typically 3-5 nm and , respectively. Due to the regularly distributed Ag NCs with high density, uniform memory characteristics and high program efficiency were achieved from NMOSFETs embedded with the Ag NCs, which were fabricated by the gate-last process.     

Glycyrrhetinic Acid Functionalized Graphene Oxide for Mitochondria Targeting and Cancer Treatment In Vivo

Mitochondria‐mediated apoptosis (MMA) is a preferential option for cancer therapy due to the presence of cell‐suicide factors in mitochondria, however, low permeability of mitochondria is a bottleneck for targeting drug delivery. In this paper, glycyrrhetinic acid (GA), a natural product from Glycyrrhiza glabra, is found to be a novel mitochondria targeting ligand, which can improve mitochondrial permeability and enhance the drug uptake of mitochondria. GA‐functionalized graphene oxide (GO) is prepared and used as an effective carrier for targeted delivery of doxorubicin into mitochondria. The detailed in vitro and in vivo mechanism study shows that GA‐functionalized GO causes a decrease in mitochondrial membrane potential and activates the MMA pathway. The GA‐functionalized drug delivery system demonstrates highly improved apoptosis induction ability and anticancer efficacy compared to the non‐GA‐functionalized nanocarrier delivery system. The GA‐functionalized nanocarrier also shows low toxicity, suggesting that it can be a useful tool for drug delivery.     

Intracellular delivery of cysteine protease inhibitor cystatin by polymeric nanoparticles

Two polymers chitosan and poly(lactide-co-glycolide) copolymer (PLGA) were investigated to develop nanoparticles (NPs) for delivery of protein drug substance into tumour cells. Cystatin was selected as a model protein drug due to its high potential to inhibit cysteine proteases, known to trigger the invasive process. Ionotropic gelation of chitosan with tripolyposphate and precipitation of PLGA polymer from a double emulsion system by a solvent diffusion process were used to produce 250-300 nm in diameter NPs. The cellular uptake of NPs was tested on a transformed human breast epithelial cell line, MCF-10A neoT, characterized by an increased expression of cysteine proteases and highly invasive cell phenotype. The influence of NPs on cell viability was evaluated by MTT test showing IC50 400 microg/ml for PLGA and 5 mg/ml for chitosan NPs. As determined by fluorescence microscopy chitosan NPs did not enter the cells during 1-hour incubation whereas the same amount of PLGA NPs were in the cells already after 5 min of incubation. Cystatin delivered into MCF-10A neoT cells by PLGA NPs effectively inhibited intracellular proteolytic activity of cathepsin B, as detected by specific fluorogenic substrate Z-Arg2 cresyl violet. On the contrary, free cystatin in solution did not internalise into the cells and inhibit cathepsin B. To conclude, PLGA NPs with cystatin but not chitosan NPs were targeted through endocytosis to the lysosomal compartments that are rich of proteases enzymes. Our results suggest new strategy to inactivate intracellular tumour-associated proteases, and consequently the invasion behaviour of tumour cells, which could contribute to cancer therapy.     

作用于线粒体和细胞核的聚合物纳米材料及其在化疗/光热治疗联合抗癌中的应用

开发本身即具有线粒体靶向能力的亚细胞精准纳米诊疗试剂对于改善癌症治疗效果具有重要意义.本文使用可靶向癌细胞表面过度表达的CD44抗原的透明质酸、胆固醇-聚乙二醇-氨基和可作用于线粒体的花菁类染料IR825-NH2,构建了一种可实现光热治疗的自组装纳米材料(HA-IR825-Chol).相较于游离的IR825-NH2,该结构具有更好的光稳定性、更高的光热转换效率和对癌细胞的识别能力.HA-IR825-Chol可以有效靶向细胞线粒体,并可以在近红外激光照射下诱导线粒体损伤.此外,我们通过疏水作用包裹了化疗试剂10-羟基喜树碱(HCPT)(所形成的药物命名为HAIR825-Chol/HCPT).相关实验结果显示,包裹于纳米材料后HCPT被细胞摄取的效率显著提高,并能够同时分布于线粒体和细胞核中,从而诱导线粒体中细胞色素c的释放和细胞中cleaved caspase-3的上调,最终促进细胞凋亡与死亡.另外,HA-IR825-Chol/HCPT优异的体内肿瘤靶向能力为光化疗联合治疗消除肿瘤提供了必要保证.该工作实现了定位于线粒体的精准亚细胞药物递送,并发展了利用胆固醇提高药物摄取速率和效率的策略,预期将为提高纳米药物抗癌效果提供借鉴.     

Hepatic histopathological and ultrastructural alterations induced by 10 nm silver nanoparticles

Silver nanoparticles (Ag NPs) are invested in various sectors and are becoming more persistent in our ambient environment with potential risk on our health and the ecosystems. The current study aims to investigate the histological, histochemical and ultrastructural hepatic changes that might be induced by 10 nm silver nanomaterials. Male mice (BALB/C) were exposed for 35 injections of daily dose of 10 nm Ag NPs (2 mg/kg). Liver tissues were subjected to examination by light and electron microscopy for histological, histochemical and ultrastructural alterations. Exposure to Ag NPs induced Kupffer cells hyperplasia, sinusoidal dilatation, apoptosis, ground glass hepatocytes appearance, nuclear changes, inflammatory cells infiltration, hepatocytes degeneration and necrosis. In addition, 10 nm Ag NPs induced histochemical alterations mainly glycogen depletion with no hemosiderin precipitation. Moreover, these nanomaterials exhibited ultrastructure alterations including mitochondrial swelling and cristolysis, cytoplasmic vacuolation, apoptosis, multilammellar myelin figures formation and endoplasmic destruction and reduction. The findings revealed that Ag NPs can induce alterations in the hepatic tissues, the chemical components of the hepatocytes and in the ultrastructure of the liver. One may also conclude that small size Ag NPs, which are increasingly used in human products could cause various toxigenic responses to all hepatic tissue components.Inspec keywords: liver, electron microscopy, molecular biophysics, optical microscopy, toxicology, biochemistry, silver, biological tissues, nanofabrication, cellular biophysics, biomedical materials, nanoparticles, nanomedicineOther keywords: hepatic histopathological alterations, ultrastructural alterations, silver nanoparticles, histological changes, histochemical changes, ultrastructural hepatic changes, silver nanomaterials, male mice, liver tissues, electron microscopy, histological alterations, histochemical alterations, Kupffer cells hyperplasia, sinusoidal dilatation, apoptosis, ground glass hepatocytes appearance, inflammatory cells infiltration, hepatocyte degeneration, necrosis, ultrastructure alterations, Ag, size 10.0 nm, hepatic tissue components, cytoplasmic vacuolation     

Efficient delivery of antitumor drug to the nuclei of tumor cells by amphiphilic biodegradable poly(L-aspartic acid-co-lactic acid)/DPPE co-polymer nanoparticles

The use of biodegradable polymeric nanoparticles (NPs) for controlled drug delivery has shown significant therapeutic potential. Polyaspartic acid and polylactic acid are the most intensively studied biodegradable polymers. In the present study, novel amphiphilic biodegradable co-polymer NPs, poly(L-aspartic acid-co-lactic acid) with 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE) (poly(AA-co-LA)/DPPE) is synthesized and subsequently used to encapsulate an antitumor drug doxorubicin (DOX). The formulation parameters of the NPs are optimized to improve encapsulation efficiency. The resulting drug-loaded NPs possess better size homogeneity (polydispersity) and exhibit pH-responsive drug release profiles. Cellular viability assays indicate that the poly(AA-co-LA)/DPPE NPs did not induce cell death, whereas doxorubicin encapsulated NPs were cytotoxic to various types of tumor cells. In addition, the free NPs could not enter the cell nuclei after internalized in tumor cells. The DOX-loaded NPs exhibit efficient intracellular delivery in tumor cells with co-localization in lysosome and delay entering into the nucleus, which suggests a time- and pH-dependent drug release profile within cells. When applied to deliver chemotherapeutics to a mouse xenograft model of human lung adenocarcinoma, DOX-loaded NPs have a comparable antitumor activity with free DOX, and greatly reduce systemic toxicity and mortality. The delivery of cytotoxic drugs directly to the nucleus specifically within tumor cells is of great interest. These results demonstrate the feasibility of the application of the amphiphilic polyaspartic acid derivative, poly(AA-co-LA)/DPPE, as a nanocarrier for cell nuclear delivery of potent antitumor drugs.     

Functionalised gold nanoparticles for selective induction of in vitro apoptosis among human cancer cell lines

The interaction of citrate- and polyethylene imine (PEI)-functionalised gold nanoparticles (GNP) with cancer cell lines with respect to the cellular response was studied. It was found that GNP/citrate nanoparticles were able to induce apoptosis in human carcinoma lung cell lines A549, but GNP/PEI did not show any reduction in the viability of the cells in human breast cancer cell line MCF-7 and A549 cell lines. FACS data confirmed that the number of apoptotic cells increased with increase in the concentration of GNP/citrate nanoparticles. Decline in cellular expansion and changes in the nuclear morphology were noted after the treatment of GNP/citrate nanoparticles on A549 cell lines, which itself is a direct response for stress induction. The induction of cellular apoptosis was further confirmed by DNA fragmentation assay. These data confirm the potential of GNP/citrate nanoparticle to evoke cell-specific death response in the A549 cell lines.     

Analysis of the cytotoxicity of differentially sized titanium dioxide nanoparticles in murine MC3T3-E1 preosteoblasts

There is an increased use of nanophase titanium dioxide (TiO₂) in bone implants and scaffolds. However, nano-debris is generated at the bone-biomaterial interface. Therefore, TiO₂ nanoparticles (NPs) of many sizes were investigated for cytotoxic effects on murine MC3T3-E1 preosteoblasts. These TiO₂ NPs induced a time- and dose-dependent decrease in cell viability. There was a significant increase in lactate dehydrogenase (LDH) release, apoptosis and mitochondrial membrane permeability following short-term exposure of the cells to TiO₂ NPs. These NPs also increased granulocyte-macrophage colony stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) gene expression. Compared with the 32 nm TiO₂ NPs, 5 nm TiO₂ NPs were more toxic, induced more apoptosis, increased mitochondrial membrane permeability and stimulated more GM-CSF expression at a high concentration (≥100 μg/ml). The results implied that the differential toxicity was associated with variations in size, so more attention should be given to the toxicity of small NPs for the design of future materials for implantation.