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In the following research, we specifically assessed the feasibility of a novel AS-1411-chitosan (CS)-gold nanoparticle (AuNPs) delivery system to carry methotrexate (MTX) into the cancer cells. The designed system had a spherical shape with average size of 62 ± 2.4 nm, the zeta potential of −32.1 ± 1.4 mV, and released MTX in a controlled pH- and time-dependent manner. CS-AuNPs could successfully penetrate the breast cancer cells and release the therapeutic drug, and ultimately, be accumulated by the nucleolin-AS1411 targeting mechanism within the in vivo environment. The anticancer activity of MTX was attributed to the induction of mitochondria membrane potential loss and nuclear fragmentation, which leads to apoptotic death. Moreover, the cellular internalization confirmed the high potential in the elimination of cancer cells without notable cytotoxicity on non-target cells. Therefore, it was concluded that the AS1411-CS-AuNPs with considerable in vitro and in vivo results could be utilized as a favorable system for breast cancer treatment.

To date, the use of nanocarriers has been developed in various fields, especially in cancer treatment. Graphene oxide (GO) is a novel drug delivery system that eagerly attracts the attention of many researchers due to its unique features. For the first time, a biocompatible AS1411 APT-GO-COOH was synthesized for the co-delivery of chemotherapeutics and herbal drugs. Here, a human gastric adenocarcinoma cell line (AGS) was targeted with aptamer-carboxylated graphene oxide (APT-CGO) containing anticancer drugs (curcumin (CUR) and doxorubicin (DOX)). The current study aimed to assess the anti-cancer effect of combination therapy, as well as target genes and proteins interfering in the development of gastric cancer. After attachment of APT to CGO, the drugs (CUR and DOX) were loaded on the carrier, establishing a co-delivery system. Then, physical characteristics, release profile, cytotoxicity assay, cellular uptake, expression rates of the genes (RB1, CDK2, AKT, and NF-KB) and proteins (RB1, CDK2), and the apoptosis rate were determined. The designed co-delivery system for the drugs (CUR and DOX) and APT showed a thermo- and pH-sensitive drug release behavior that successfully reduced the expression of CDK2, AKT, and NF-KB while it enhanced RB1 expression at the gene and protein levels. Also, APT-CGO-drugs were successfully targeted to the AGS cell line, leading to a highly inhibitory property against this cell line compared to CGO-drugs. It seems that the co-delivery of CUR and DOX along with APT as a targeting agent was more effective than CGO-drugs, suggesting a promising candidate for the treatment of gastric cancer. The results showed that this biofunctionalized nanocarrier could reduce the cytotoxicity of the drugs in normal cells and could increase efficiency.

Enhancing the therapeutic profile of hydrophobic drugs using the development of biocompatible drug delivery systems is an urgent need. Many types of research have been conducted on graphene derivatives owing to their unique characteristics.In this survey, quercetin (QUER), a natural medicine, was loaded on carboxylated graphene oxide (GO), and cytotoxicity assay and the uptake of QUER into prostate cancer cells (PC3) were evaluated.The release behavior of QUER was temperature- and pH-sensitive. Although QUER was loaded with high efficiency, the released rate was low (23.25% at pH 5.5 and 42 °C). The toxicity and intensity of fluorescence in the FREE QUER were higher than the loaded form.High-capacity loading and controlled release of GO QUER can be recognized as a proper candidate in treating cancer.

Bladder cancer is one of the concerning urological malignant diseases in the world, which has a clinical need for effective targeted therapy. The development of nanotechnology-based gene delivery to bladder tumor sites is an effective strategy for targeted cancer therapy with low/no toxicity. With this view, in the present work, the mesoporous silica nanoparticles (MSNs) modified with c(RGDfK)-PLGA-PEG [c(RGDfK)-MSN NPs] were constructed for co-delivery of miR-34a and siPD-L1 within bladder cancer cells and tissues. Our findings showed that miR-34a is downregulated while PD-L1 is up-regulated in cell lines and animal studies. This nano-carrier is biocompatible in the serum environment and effectively protects miR-34a and siPD-L1 against serum degradation. However, we showed that c(RGDfK)-MSN NPs could simultaneously downregulate PD-L1 expression and up-regulate miR-34a in the T24 cells and T24 mice model and enhance anti-tumor effects both in vivo and in vitro. In conclusion, these findings presented new suggestions for improving targeted therapeutic strategies with specified molecular objectives for bladder cancer treatment.

Introduction : Despite the applications and advantages of ionizing radiation; there are many radiation risks to biological systems that are necessary to be reduced as much as possible. The present study aimed to assess the radioprotective effect of nanoniosomes loaded by Mentha Pulegium essential oil (MPEO-N) as a natural antioxidant on human peripheral blood mononuclear cells (PBMCs). Materials and methods MPEO-N nanoparticles were prepared by the lipid thin-film hydration method, and its physicochemical characteristics were analyzed. PBMCs were then irradiated with X-ray using a 6 MV linear accelerator at radiation doses of 25 and 200 cGy in the presence of non-toxic concentrations of MPEO-N nanoparticles (IC10). After 48 and 72 h of incubation, the radioprotective effect was investigated by measuring survival, apoptosis, and necrosis of PBMCs, using MTT assay and flow cytometry analysis. Results The hydrodynamic diameter and zeta potential of nanoniosomes were 106.0 nm and − 15.2 mV, respectively. The mean survival percentage of PBMCs showed a significant increase only at a radiation dose of 200 cGy compared with the control group. The percentages of apoptosis and necrosis of cells in the presence of MPEO-N nanoparticles at both radiation doses and incubation periods (48 and 72 hours) demonstrated a significant reduction compared with the control. Conclusion MPEO-N nanoparticles as a natural antioxidant, exhibited a favorable radioprotective effect by a significant reduction in the percentage of apoptosis and necrosis of irradiated PBMCs.

Tumor suppressor miRNAs, miR-15a and miR-16–1, with high-specificity and oncogenic targeting of Bcl-2, can target tumor tissues. Disadvantages of the clinical application of free miRNAs include poor cellular uptake and instability in plasma, which can be partially improved by using nanocarriers to deliver anti-cancer agents to the tumor cell. In this study, cationic niosomes were designed and optimized with the specific formulation. Then, the physical characteristics, the cytotoxicity, the impact of transfected miRNAs on the expression of the Bcl-2 gene, and the apoptosis rate of the different formulation into prostate cancer cell were determined. The optimum formulation containing tween-60: cholesterol: DOTAP: DSPE-PEG2000 at 70:30:25:5 demonstrated that the vesicle size and zeta potentials were 69.7 nm and + 14.83 mV, respectively. Additionally, noisome-loaded miRNAs had higher toxicity against cancer cells comparing with free forms. The transfection of PC3 cells with the combination therapy of nanocarriers loaded of two miRNAs led to a significant decrease in the expression of the Bcl-2 gene and increased the degree of cell death in PC3 cells compared with other treatment groups, and the synergistic effects of co-delivery of miR-15a and miR-16–1 on prostate cancer cells were shown. According to the results, it seems the designed niosomes containing miR-15a and miR-16–1 can target the Bcl-2 gene and provide a cheap, applicable, cost-effective, and safe drug delivery system against prostate cancer.

This study aims to optimize niosomes for carrying and delivering the anticancer agents and genes, simultaneously. We synthesized new cationic niosomal formulations containing Tween 80, Tween 60, cholesterol, and dioleoyl-3-trimethylammonium propane (DOTAP) as a platform to enhance transfection efficacy and stability. Curcumin as an anticancer drug was entrapped with high efficacy inside stable spherical niosomes with sufficient positive charges of about + 27 mV. Loading niosomal curcumins with microRNA-34a (miR-34a) decreased the surface charge to + 15 mV and enhanced the diameter to near 68 nm. The in vitro studies were performed to investigate the cytotoxicity, cellular uptake, and gene expression profiling of normal and cancer cells treated by free curcumin, free miR-34a, niosomal curcumin (NCur), niosomal miR-34a (NmiR), niosomal curcumin + miR-34a (NCur-miR) which is termed as co-delivery, and niosomal curcumin + niosomal miR-34a which is termed as co-administration. Results showed that co-delivery caused more cytotoxicity, uptake, and anticancer activity in cancer cells than in other groups. Most importantly, niosomal and free forms of curcumin and miR-34a showed less toxicity to normal human cells. Besides, the effect of these anticancer agents was studied on the 4 T1 xenografted Balb/C mouse tumor model. Co-delivery of curcumin and miR-34a to cancer models caused a higher tumor inhibition rate than other groups. Thus, a combined therapy of curcumin and miR-34a using the new cationic niosomal delivery can be recognized as a prominent strategy for more effective cancer treatments.

Cisplatin is one of the conventional drugs used in chemotherapy which has a potent antitumor function. However, due to the dangerous side effects, including the damage to DNA of the normal cells, its clinical use is limited. The aim of this study was to prepare and characterize nanoliposome containing cisplatin. We optimized liposome formulations through the modification of the proportion of SPC80 (soybeanphospholipids with 75% phosphatidylcholine) and cholesterol content. Then, novel PEGylated liposomal formulations containing SPC80: cholesterol: DSPE-mPEG (at ratios of 85:10:5) were designed and developed to serve as a therapy to achieve more improved pharmaceutical efficiency. Zeta Sizer showed that PEGylated nanoliposomes had a mean diameter of 119.7 ± 2.1 nm, a zeta potential of -26.03 ± 1.34 mV, and entrapment efficiency of 96.65 ± 3%. The optimum formulations represented sustained, thermo-sensitive release, and augmented cellular uptake. The cytotoxic effect of the liposomal drug was higher than the free medication drug that confirmed the efficiency of cellular uptake. This study suggests that nanoliposome-loaded cisplatin plays a vital role in improving drug efficacy and the reduction of dosage.

Doxorubicin (DOX) is a common chemotherapy agent that is used in clinics for the treatment of a wide spectrum of cancers. Herein, a novel approach for improving doxorubicin loading on nanoparticles and also controlled release is suggested using crosslinking doxorubicin molecules with glutaraldehyde. We investigated the loading efficiency of doxorubicin on CoFe

The Mentha-Pulegium essential oil (MP-EO) contains different antioxidant compounds and reduces the indirect effects of dispersed ionizing radiation on biological systems.The current study aimed to assess a possible radio-protective effect of MP-EO on peripheral blood mononuclear cells (PBMCs).In this experimental study, MP-EO was firstly prepared and PBMCs were then irradiated in various groups with doses of 25 and 200 cGy of X-rays in the presence ofIn the presence of 80 µg/ml (MP-EO as a natural, non-toxic, and cost-effective compound can exhibit a favorable

Background: The reactive surface of nanoparticles makes it possible to simply modify with a biocompatible coating and load with therapeutic agents such as siRNA, miRNA, an anti-cancer drug, and antibody. MicroRNAs, like the noncoding RNAs, contribute critical to the regulation of numerous cellular functions via transcriptional silencing. MicroRNAs (miRNAs) have enormous potential in cancer treatment, however, it is difficult to deliver them effectively to most solid tumors. The encapsulation of miRNA-34a in niosome nanoparticles is an attractive strategy for biopharmaceutical resources against cancer. The present study investigated the effectiveness of anticancer activity against MCF-7 and T47D human breast adenocarcinoma cells of a new noiosome system composed of nonionic surfactants. Methods: We used the optimum formulations to transfer miRNA-34a to breast cancer cells, providing potential benefits, such as exceptionally high entrapment efficiency (almost 100%), spherical shape, suitable positive charge (zeta potential~ + 24 mV) and small diameter (~100 nm). Results: The miRNA-34a-niosomes represented improved cytotoxic activity against the cancer cells compared to readily dispersed miRNA-34a. The resulting data indicate that delivery of miRNA-34a via niosome can affect tumor suppression, highlighting its promising anticancer effects in breast cancer cells. Conclusion: In conclusion, the developed a new carrier to improve the delivery of miRNA-34a into the tumor cells. The formulation provided in the present work is stable with a sustained release, high efficiency of miRNA-34a loading having a diameter of 115 nm. miRNA loading is performed without potentially harmful chemical reactions. Niosomes loaded with miRNA-34a in this study represented significant cytotoxic effects against the human breast cancer MCF-7 and T47D cells, which highlights their potential effect on this type of cancer cells.

MXenes are a new class of conductive two-dimensional material which have received growing attention in biosensing for their significant surface area and unique surface chemistry. Here, gold electrodes were modified with MXene nanosheets of about 2 nm thickness and 1.5 μm lateral size for the electrochemical detection of tumor cells. An HB5 aptamer with high selectivity for HER-2 positive cells was immobilized on the MXene layers via electrostatic interactions. To minimize electrode biofouling with blood matrix, magnetic separation of HER-2 positive circulating tumor cells was carried out using CoFe

MXenes are a new class of conductive two-dimensional material which have received growing attention in biosensing for their significant surface area and unique surface chemistry. Here, gold electrodes were modified with MXene nanosheets of about 2 nm thickness and 1.5 μm lateral size for the electrochemical detection of tumor cells. An HB5 aptamer with high selectivity for HER-2 positive cells was immobilized on the MXene layers via electrostatic interactions. To minimize electrode biofouling with blood matrix, magnetic separation of HER-2 positive circulating tumor cells was carried out using CoFe2O4@Ag magnetic nanohybrids bonded to the HB5. The formation of sandwich-like structures between the magnetically captured cells and the functionalized MXene electrodes effectively shields the electron transfer of a redox probe, enabling quantitative cell detection using the change in current. This label-free MXene-based cytosensor platform yielded a wide linear range of 102-106 cells/mL, low detection limit of 47 cells/mL, and good sensitivity and selectivity in the detection of HER2-posetive cells in blood samples. The presented aptacytosensor demonstrates the great potential of using CoFe2O4@Ag magnetic nanohybrids and MXenes to monitor cancer progression via circulating tumor cells in blood at low cost.

The aim of this study was to optimize the cationic PEGylated niosome-containing anti-cancer drugs and siRNA to enhance the therapeutic response. Therefore, various surfactant-based (tween-60) vesicles of doxorubicin (DOX; a chemotherapeutic drug) and quercetin (QC; a chemosensitizer) were prepared. To load siRNA on niosomes, 1, 2-dioleoyl-3-trimethylammonium-propane (DOTAP) was used as a cationic lipid. The optimum formulation containing tween-60:cholesterol:DPPC:DOTAP:DSPE-PEG2000 at 49.5:5.5:15:25:5 demonstrated that the vesicle size and zeta potential were 52.8 ± 2.7 nm and +27.4 ± 2.3 mV, respectively. Entrapment efficiency (EE%) for DOX and QC was 86.4 ± 2.1% and 94.9 ± 3.9%, respectively. Moreover, the drug release during 6 h was 32.1 ± 1.6% and 30.5 ± 1.3% for DOX and QC, respectively denoted on the controlled release. The gel retardation assay demonstrated that siRNA could be successfully loaded into a cationic niosome:siRNA in a weight ratio 40:1. Additionally, noisome-encapsulated drugs had a higher toxicity against cancer cells when compared with un-encapsulated forms and the synergistic effects of co-delivery of siRNA and DOX with QC on gastric, prostate, breast cancer cells as well as human foreskin fibroblast as a normal cell line was shown. The results showed that the co-delivery of drugs and siRNA using cationic PEGylated niosomes exhibited an increased anti-cancer activity against the tumor cell death. It seems that cationic PEGylated niosomes have opened up a new avenue to enrich the armamentarium of therapeutic agents to fight cancer.

Background The systemic administration of cytotoxic chemotherapeutic agents for cancer treatment often has toxic side effects, limiting the usage dose. To increase chemotherapeutic efficacy while reducing toxic effects, a rational design for synergy-based drug regimens is essential. This study investigated the augmentation of therapeutic effectiveness with the co-administration of paclitaxel (PTX; an effective chemotherapeutic drug for breast cancer) and curcumin (CUR; a chemosensitizer) in an MCF-7 cell line. Results We optimized niosome formulations in terms of surfactant and cholesterol content. Afterward, the novel cationic PEGylated niosomal formulations containing Tween-60: cholesterol:DOTAP:DSPE-mPEG (at 59.5:25.5:10:5) were designed and developed to serve as a model for better transfection efficiency and improved stability. The optimum formulations represented potential advantages, including extremely high entrapment efficiency (~ 100% for both therapeutic drug), spherical shape, smooth-surface morphology, suitable positive charge (zeta potential ~ + 15 mV for both CUR and PTX), sustained release, small diameter (~ 90 nm for both agents), desired stability, and augmented cellular uptake. Furthermore, the CUR and PTX kinetic release could be adequately fitted to the Higuchi model. A threefold and 3.6-fold reduction in CUR and PTX concentration was measured, respectively, when the CUR and PTX was administered in nano-niosome compared to free CUR and free PTX solutions in MCF-7 cells. When administered in nano-niosome formulations, the combination treatment of CUR and PTX was particularly effective in enhancing the cytotoxicity activity against MCF-7 cells. Conclusions Most importantly, CUR and PTX, in both free form and niosomal forms, were determined to be less toxic on MCF-10A human normal cells in comparison to MCF-7 cells. The findings indicate that the combination therapy of PTX with CUR using the novel cationic PEGylated niosome delivery is a promising strategy for more effective breast cancer treatment.

This study focuses on the development of a universal mathematical model for drug release kinetics from liposomes to allow in silico prediction of optimal conditions for fine-tuned controlled drug release. As a prelude for combined siRNA-drug delivery, nanoliposome formulations were optimized using various mole percentages of a cationic lipid (1,2-dioleoyl-3-trimethylammonium-propane, DOTAP) in the presence or absence of 3 mol% distearoyl phosphoethanolamine, polyethylene glycol (PEG–2000mDSPE). Outcome parameters were particle size, zeta potential, entrapment efficiency, in vitro drug release, and tumor cell kill efficiency. The optimized formula (containing 20% DOTAP with 3% DSPE-mPEG(2000) was found to be stable for six months, with round-shaped particles without aggregate formation, an average diameter of 71 nm, a suitable positive charge, and 89% drug encapsulation efficiency (EE). The 41% drug release during 6 h confirmed controlled release. Furthermore, the release profiles as functions of pH and temperature were investigated and the kinetics of the drug release could adequately be fitted to Korsmeyer–Peppas’ model by multiple regression analysis. The statistical parameters confirmed good conformity of final models. Functionality of the novel cationic liposome formulations (± DOX) was tested on osteosarcoma (OS) cell lines. Increased OS cell toxicity (1.3-fold) was observed by the DOX-loaded vs. the free DOX. A feasibility pilot showed that siRNA could be loaded efficiently as well. In conclusion, we have established a predictive mathematical model for the fine-tuning of controlled drug release from liposomal formulations, while creating functional drug-delivery liposomes with potential for siRNA co-delivery to increase specificity and efficacy. (Figure presented.)

For decades, multi-drug resistance (MDR) to chemotherapeutic drugs has been a serious challenge for researchers and has limited the use of anticancer drugs in malignancy treatment. Combination therapy has been considered as one of the most promising methods to address this problem. In the current study, we optimized niosome nanoparticles containing chemotherapeutic agent doxorubicin and chemosensitizer curcumin in term of surfactant content. Then, a new biocompatible structure (LipoNiosome, combination of niosome and liposome) containing Tween 60: cholesterol: DPPC (at 55 : 30 : 15 : 3) with 3% DSPE-mPEG was designed and developed to serve as a model for selective co-delivery of hydrophilic and hydrophobic drugs to cancerous cells. The proposed formulation provided potential benefits, including pH-sensitive sustained release, smooth globular surface morphology, high entrapment efficiency (∼80% for both therapeutic agents) and small diameter (42 nm). Exposure of cancer cells to LipoNiosome-doxorubicin–curcumin has shown an excellent performance of specific cellular internalization and synergistic toxic effect (>40%; as compared to free drugs and >23% when compared to single doxorubicin delivery) against Saos-2, MG-63 and KG-1 cell lines. A new cationic formulation (zeta potential: +35.26 mV; diameter: 52.2 nm) was also designed for co-delivery of above-mentioned drugs and gene as well. Finely, we suggested a kinetic model (Korsmeyer–Peppa with R2 = 93% near cancer cells) for in vitro drug release of the co-delivery system. The presently formulated nano-based systems would provide researchers with a more obvious understanding of new LipoNiosome formulation as a successful lipid-based nano-carriers for co-delivery of doxorubicin, curcumin and other anticancer agents.

Fateme Haghiralsadat,1–3 Ghasem Amoabediny,3–5 Samira Naderinezhad,4 Behrouz Zandieh-Doulabi,6 Tymour Forouzanfar,5 Marco N Helder5 1Department of Life Science Engineering, Faculty of New Sciences and Technologies, University of Tehran, Tehran, Iran; 2Department of Orthopaedic Surgery, VU University Medical Center, MOVE Research Institute Amsterdam, Amsterdam, the Netherlands; 3Department of Nano Biotechnology, Research Center for New Technologies in Life Science Engineering, 4Department of Biotechnology and Pharmaceutical Engineering, School of Chemical Engineering, College of Engineering, University of Tehran, Tehran, Iran; 5Department of Oral and Maxillofacial Surgery, VU University Medical Center, MOVE Research Institute Amsterdam, 6Department of Oral Cell Biology and Functional Anatomy, Academic Center for Dentistry Amsterdam (ACTA), Vrije Universiteit Amsterdam and University of Amsterdam, MOVE Research Institute, Amsterdam, the Netherlands Purpose: Osteosarcoma (OS) mostly affects children and young adults, and has only a 20%–30% 5-year survival rate when metastasized. We aimed to create dual-targeted (extracellular against EphA2 and intracellular against JNK-interacting protein 1 [JIP1]), doxorubicin (DOX)-loaded liposomes to treat OS metastatic disease. Materials and methods: Cationic liposomes contained N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium methyl-sulfate (DOTAP), cholesterol, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), and distearoyl-phosphatidylethanolamine–methyl-poly(ethylene glycol) (DSPE–mPEG) conjugate. EphA2 targeting was accomplished by conjugating YSA peptide to DSPE–mPEG. Vesicles were subsequently loaded with DOX and JIP1 siRNA. Results: Characteristics assessment showed that 1) size of the bilayered particles was 109nm; 2) DOX loading efficiency was 87%; 3) siRNA could be successfully loaded at a liposome:siRNA ratio of >24:1; and 4) the zeta potential was 18.47mV. Tumor-mimicking pH conditions exhibited 80% siRNA and 50.7% DOX sustained release from the particles. Stability studies ensured the protection of siRNA against degradation in serum. OS cell lines showed increased and more pericellular/nuclear localizations when using targeted vesicles. Nontargeted and targeted codelivery caused 70.5% and 78.6% cytotoxicity in OS cells, respectively (free DOX: 50%). Targeted codelivery resulted in 42% reduction in the siRNA target, JIP1 mRNA, and 46% decrease in JIP1 levels. Conclusion: Our dual-targeted, DOX-loaded liposomes enhance toxicity toward OS cells and may be effective for the treatment of metastatic OS. Keywords: MAP kinase 8 interacting protein 1, MAPK8IP1, functionalization, cationic liposome, intracellular targeting, extracellular targeting

A wide number of drug nanocarriers have emerged to improve medical therapies, and in particular to achieve controlled delivery of drugs, genes or gene expression-modifying compounds, or vaccine antigens to a specific target site. Of the nanocarriers, lipid-based and polymeric nanoparticles are the most widely used. Lipid-based systems like niosomes and liposomes are non-toxic self-assembly vesicles with an unilamellar or multilamellar structure, which can encapsulate hydrophobic/hydrophilic therapeutic agents. Polymeric nanoparticles, usually applied as micelles, are colloidal carriers composed of biodegradable polymers. Characteristics such as loading capacity, drug release rate, physical and chemical stability, and vesicle size are highly dependent on experimental conditions, and material and method choices at the time of preparation. To be able to develop effective methods for large scale production and to meet the regulatory requirements for eventual clinical implementation of nanocarriers, one needs to have in-depth knowledge of the principles of nanoparticle preparation. This review paper presents an overview of different preparation methods of polymeric and novel lipid-based (niosome and solid lipid) nanoparticles.

Cationic liposomes have been investigated as non-viral vectors for gene delivery for more than a decade to overcome challenges associated with viral gene delivery. However, due to instability of liposomes, siRNA delivery is still a serious problem. In this study, we developed stealth PEGylated liposome formulations and focused on the effects of PEGylated liposomes on parameters related to size, zeta potential, polydispersity index, siRNA-loading efficiency and long-term stability of the siRNA-liposome complex. We were able to generate siRNA lipoplexes that could be very efficiently loaded, did not aggregate, could be stored at 4 °C for at least 6 months with only marginal release (1–5%) of siRNA and enhanced intracellular delivery of siRNA. Moreover, we could demonstrate that PEGylation positively contributed to all these parameters compared to liposomes, which were not PEGylated. The prepared lipoplex was successfully silenced J1P1 expression in MG-63 osteosarcoma cell line. In conclusion, our novel PEGylated liposomes have high potential for systemic delivery of siRNA and can improve in vivo stability of free siRNA and also siRNA lipoplexes.

Purpose: To employ Doxorubicin-loaded liposomes, modified with YSA-peptide to target EphA2, to reduce adverse effects against primary bone cells and maximize toxicity against Saos-2 osteosarcoma cells. Methods: PEGylated liposomes were prepared by thin film method using Dipalmitoylphosphatidylcholine (DPPC), cholesterol and distearylphosphatidylethanolamine-polyethyleneglycol conjugate (DSPE-mPEG) in 67.9:29.1:3 M ratios, and loaded with DOX (L-DOX) by pH-gradient method. Targeted liposomes (YSA-L-DOX), were prepared by conjugating YSA-peptide to DSPE-mPEG. Liposomes were physicochemically characterized and tested in cellular toxicity assays. Results: YSA conjugation efficiency was >98%. Size and polydispersity index of both L-DOX and YSA-L-DOX were around 88 nm and 0.188, respectively. Both had similar zeta potential, and 85% DOX loading efficiencies. DOX release kinetics followed the Korsmeyer-Peppa model, and showed comparable release for both formulations from 1–8 h, and a plateau of 29% after 48 h. Both formulations could be stably stored for ≥6 months at 4°C in the dark. Toxicity assays showed a significant 1.91-fold higher cytotoxicity compared to free DOX in the Saos-2 cells, and 2-fold lesser toxicity in primary bone cells compared to the Saos-2 cells. Cellular uptake studies showed higher and more nuclear uptake in YSA-L-DOX compared to L-DOX treated cells. Conclusions: YSA-L-DOX vesicles might be effective for targeted treatment of osteosarcoma.

A novel approach was developed for the preparation of stealth controlled-release liposomal doxorubicin. Various liposomal formulations were prepared by employing both thin film and pH gradient hydration techniques. The optimum formulation contained phospholipid and cholesterol in 1:0.43 molar ratios in the presence of 3% DSPE-mPEG (2000). The liposomal formulation was evaluated by determining mean size of vesicle, encapsulation efficiency, polydispersity index, zeta potentials, carrier's functionalization, and surface morphology. The vesicle size, encapsulation efficiency, polydispersity index, and zeta potentials of purposed formula were 93.61 nm, 82.8%, 0.14, and −23, respectively. Vesicles were round-shaped and smooth-surfaced entities with sharp boundaries. In addition, two colorimetric methods for cytotoxicity assay were compared and the IC50 (the half maximal inhibitory concentration) of both methods for encapsulated doxorubicin was determined to be 0.1 μg/ml. The results of kinetic drug release were investigated at several different temperatures and pH levels, which showed that purposed formulation was thermo and pH sensitive.

The fabrication of a mechanically flexible piezoresistive load sensor is reported. Inkjet printing offers an inexpensive non-contact fabrication method for microelectronics. Herein we report the first direct fabrication of inkjet-printed graphene arrays, and apply them to electromechanical detection of force. The graphene ink was printed on a cantilever shape paper substrate. The results illustrated a linear resistance change with the applied forces. The force range, force resolution, and sensitivity were found to be 25 mN, 10 μN, and 1.2 mV/mN, respectively. In addition, graphite ink was also used as the sensing component in order to make a comparison between the piezoresistive effect of graphene and graphite ink. The results show that using graphene ink instead of graphite increases the force range and gauge factor of the sensor, which are two important designing factors. This sensor is inexpensive, simple to fabricate, lightweight, and disposable.

In this work, a signal transduction biosensor has been used as a novel electrical detection for identifying prostate specific antigen (PSA), a protein biomarker associated with prostate cancer. A direct nano-mechanical response of micro-fabricated self-sensing nanomechanical membrane (NMM) was used to detect the surface stress changes of antigen–antibody specific binding. The sensing principle is based on the surface stress changes induced by antigen–antibody interaction on the NMM surfaces. NMM consists of a membrane suspended by four piezoresistive sensing components. The isotropic surface stress on the membrane results in an uniaxial stress in each sensing component, which efficiently improves the sensitivity. After injecting the PSA target, as model biocontents, the piezoresistive responses were carefully analyzed and the feasibility of the piezoresistive membranes for biosensing were discussed in terms of device performance measures such as sensitivity, accuracy, and specificity. At the end, the results were compared with a standard cantilever.

The fabrication of a mechanically flexible load sensor is reported. The sensor has the shape of cantilever beam on the paper substrate. Multi-walled carbon nanotubes (MWNTs) ink was used as the sensing component because of its piezoresistive and electromechanical properties. In addition, simple carbon ink was also used as the sensing component in order to make a comparison between the piezoresistive effect of MWNTs ink and simple carbon ink. The results showed that using MWNTs ink instead of simple carbon increased the range of linearity and gauge factor of the sensor which are two important designing factors. This sensor is inexpensive, simple to fabricate, lightweight, and disposable.

A Microcantilevers resonator is used to detect a protein biomarker called prostate specific antigen (PSA), which is associated with prostate cancer. Different concentrations of PSA in a buffer solution are detected as a function of deflection of the beams. For this purpose, we use a surface micromachined, antibody-coated polycrystalline silicon micromechanical cantilever beam. Cantilevers have mass sensitivities of the order of 10–17 g/Hz, which result from their small mass. This matter allows them to detect an immobilized antibody monolayer corresponding to a mass of about 70 fg. With these devices, concentrations as low as 150 fg/mL, or 4.5 fM, could be detected from the realistic samples.

We have used arrays of micromechanical biosensors to detect carcinoembryonic antigen (CEA), a protein biomarker associated with various cancers such as colorectal, lung, breast, pancreatic, and bladder cancer. The sensing principle is based on the surface stress changes induced by antigen–antibody interaction on the micromechanical membrane (MM) surfaces. MM consists of a membrane suspended by four piezoresistive sensing components. The isotropic surface stress on the membrane results in a uniaxial stress in each sensing component, which efficiently improves the sensitivity. According to the experiments, it was revealed that MMs have surface stress sensitivities in the order of 2 (mJ/m). This matter allows them to detect CEA concentrations as low as 500 pg mL-1 or 3 pM. This indicates the fact that the self-sensing MM approach is beneficial for pathological tests.