Biosynthesis and characterisation of solid lipid nanoparticles and investigation of toxicity against breast cancer cell line

Solid lipid nanoparticles (SLNs) comprise non‐toxic surface‐active lipidic agents combined with appropriate ratios of drugs or essential oils. The goal of this research was to investigate the effects of the SLN synthesised using essential oils of Foeniculum vulgare on the MCF‐7 breast cancer cell line. SLNs were prepared by homogenisation and ultrasound techniques and characterised by dynamic light scattering (DLS), zeta potential assessment, and transmission electron microscopy (TEM). 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide assay (MTT assay), flow‐cytometry, and Acridine‐Orange assay were employed for assessing the biological activities of the SLNs. The average particle size was 55.43 nm and the net surface charge was −29.54 ± 11.67 mV. TEM showed that the mean particle size was 33.55 nm and the synthesised SLNs had a uniform round morphology. The MTT assay showed that the prepared SLNs had high toxicity against MCF‐7 cells and low toxicity against normal HUVECs cells. Flow‐cytometry revealed a noteworthy rise in the subG1 peak of the cell cycle in the cancer cells treated with SLNs compared to the controls, indicating apoptosis in cancer cells. The results also showed discolouration in SLNs‐treated cells, which further confirmed the induction of apoptosis and the toxicity of the SLNs against MCF‐7 cells.     

1,3-dimethyl-6-nitroacridine derivatives induce apoptosis in human breast cancer cells by targeting DNA

The acridine derivatives can interact with the double-stranded DNA, which is regarded as the biological target of the anticancer drugs in cancer treatment. We designed and synthesized a new series of 1,3-dimethyl-6-nitroacridine derivatives as potential DNA-targeted anticancer agents. These compounds could partially intercalate into the calf thymus DNA, differing from the parent acridine. The results showed that the substitutions of the acridine ring had great effect on DNA binding affinity. The binding constants determined by UV-vis spectroscopy were found to be 10⁵?M^?1 grade. Anticancer activity of these compounds was screened using MTT assay. Most compounds inhibited 50% cancer cell growth at concentration below 30?μM, the results were consistent with the DNA binding ability. Compounds 1 and 6 were found to have more effective cytotoxicity, especially in human breast cancer cell lines. To investigate the action mechanism, we studied cell apoptosis, morphological changes, and cell cycle distribution in MCF-7 and MDA-MB-231 cells. Compounds 1 and 6 caused MCF-7 and MDA-MB-231 cells death due to apoptosis, and induced cell apoptosis in a dose-dependent manner. They also had significant effect on cell cycle progression and arrested cell cycle at G2/M phase. The results demonstrated that compounds 1 and 6 are promising candidates for cancer treatment.     

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.     

Folic acid-functionalized niosomal nanoparticles for selective dual-drug delivery into breast cancer cells: An in-vitro investigation

In this study, a folic acid-functionalized niosome was formulated and loaded with letrozole and curcumin as a promising drug carrier system for chemotherapy of the breast cancer cells. The formulation process was optimized by varying the type of Span 80 and total lipid to drug ratio, where Span 80 and lipid to drug molar ratio of 10 resulted in the niosomes with maximum encapsulation of both drugs but minimum size. The developed niosomal formulation showed a great storage stability up to one month with the small changes in drug encapsulation efficiency and size during the storage. In addition, they showed a pH-dependent release behaviour with slow drug release at physiological pH (7.4) while considerable drug release in acidic conditions (pH = 3), making it a promising candidate for breast cancer treatment. The cytotoxicity study shows the niosomal formulation has high biocompatibility with HEK-293 healthy cells, while having remarkable inhibitory effects on MCF-7 and MDA-MB-231 breast cancer cells due to the presence of folic acid in formulation, and in turn, selective internalization of the as-developed nanocarrier through folate receptor-mediated endocytosis. The double drug-loaded niosomes affect the gene expression by studied breast cancer cell lines; down-regulates the expression of Bcl2, cyclin D, and cyclin E genes while they up-regulate the expression of p53, Bax, caspase-3, and caspase-9 genes. The flow cytometry results showed that letrozole/curcumin-loaded niosomes enhanced the apoptosis rate in both MCF-7 and MDA-MB-231 cells compared to the mixture of letrozole and curcumin, which was due to the synergic effect between the two drugs as well as higher cell uptake by niosomal formulation. The findings of our study show the importance of developing highly biocompatible niosomal formulations in the future of nanomedicine that enables the co-delivery of two hydrophobic drugs into the cancer cells improves the efficiency of chemotherapy due to the synergic effect between the drugs.     

Graphene as a nanocarrier for tamoxifen induces apoptosis in transformed cancer cell lines of different origins

A cationic amphiphile, cholest-5en-3β-oxyethyl pyridinium bromide (PY(+) -Chol), is able to efficiently disperse exfoliated graphene (GR) in water by the physical adsorption of PY(+) -Chol on the surface of GR to form stable, dark aqueous suspensions at room temperature. The GR-PY(+) -Chol suspension can then be used to solubilize Tamoxifen Citrate (TmC), a breast cancer drug, in water. The resulting TmC-GR-PY(+) -Chol is stable for a long time without any precipitation. Fluorescence emission and UV absorption spectra indicate the existence of noncovalent interactions between TmC, GR, and PY(+) -Chol in these suspensions. Electron microscopy shows the existence of segregated GR sheets and TmC 'ribbons' in the composite suspensions. Atomic force microscopy indicates the presence of 'extended' structures of GR-PY(+) -Chol, which grows wider in the presence of TmC. The slow time-dependent release of TmC is noticed in a reconstituted cell culture medium, a property useful as a drug carrier. TmC-GR-PY(+) -Chol selectively enhanced the cell death (apoptosis) of the transformed cancer cells compared to normal cells. This potency is found to be true for a wide range of transformed cancer cells viz. HeLa, A549, ras oncogene-transformed NIH3T3, HepG2, MDA-MB231, MCF-7, and HEK293T compared to the normal cell HEK293 in vitro. Confocal microscopy confirmed the high efficiency of TmC-GR-PY(+) -Chol in delivering the drug to the cells, compared to the suspensions devoid of GR.     

Positive regulation of biochemical parameters by tea polyphenol encapsulated solid lipid nanoparticles at in vitro and in vivo conditions

Tea polyphenols (TPPs) comprise preventive and therapeutic potentials against cancer, cardiovascular and neurological disorders. Chemical instability of TPP which leads to low bioavailability is the major constrain to its use as therapeutic agent. The authors prepared TPP encapsulated solid lipid nanoparticles (TPP‐SLNs) to increase its stability and bioefficacy. Comparison of Fourier transformed infrared spectra of unloaded SLN, free TPP and TPP‐SLN indicated encapsulation of TPP. Sustained release of TPP from TP‐SLN was observed. TPP‐SLN showed prolonged free radical scavenging activity compared with free TPP indicating protection of TPP. TPP‐SLN showed activation of Caspases‐9 and ‐3 cascades in breast cancer cell line (Michigan cancer foundation (MCF)‐7) at in vitro conditions. Biochemical parameters were altered in Ehrlich ascetic carcinoma (EAC) cell bearing mice compared with normal (uninduced) mice which were ameliorated significantly by oral feeding of TPP‐SLN. Oral administration (pre‐ and post‐treated) of TPP‐SLN in EAC bearing mice resulted in significant increase of plasma haemoglobin, glucose, superoxide dismutase and catalase when compared with EAC bearing control mice. Other biochemical parameters (cholesterol, bilirubin, triglyceride, urea, total protein, alanine aminotransferase, alkaline phosphatase and aspertate transaminase were significantly decreased on oral administration (pre‐ and post‐treated) of TPP‐SLN in EAC bearing mice.Inspec keywords: biochemistry, nanomedicine, nanoparticles, free radicals, cancer, enzymes, patient treatmentOther keywords: positive regulation, biochemical parameters, tea polyphenol encapsulated solid lipid nanoparticles, in vitro conditions, in vivo conditions, preventive potentials, therapeutic potentials, cardiovascular disorders, neurological disorders, catalase, superoxide dismutase, glucose, plasma haemoglobin, oral feeding, EAC cell, Ehrlich ascetic carcinoma, MCF‐7, breast cancer cell line, free radical scavenging activity, encapsulation, TPP‐SLN, free TPP, unloaded SLN, Fourier transformed infrared spectra, bioefficacy, therapeutic agent, low bioavailability, chemical instability     

Encapsulated Conjugated Oligomer Nanoparticles for Real‐Time Photoacoustic Sentinel Lymph Node Imaging and Targeted Photothermal Therapy

Noninvasive and nonionizing imaging of sentinel lymph nodes (SLN) is highly desirable for the detection of breast cancer metastasis through sentinel lymph node biopsy. Photoacoustic (PA) imaging is an emerging imaging technique that can serve as a suitable approach for SLN imaging. Herein, novel conjugated oligomer based nanoparticles (NPs) with strong NIR absorption, good biocompatibility, excellent PA contrast, and good photothermal conversion efficiency are reported. Real‐time PA imaging of SLN reveals high resolution of the NPs via injection from the left forepaw pad. In addition, the surface functionalized NPs can target breast cancer cells and kill them efficiently and specifically through photothermal therapy upon 808 nm laser irradiation. This work shows great potential of the nanoparticle PA contrast agent to serve as a multifunctional probe for photothermal therapy at SLNs to achieve the inhibition of cancer cell metastasis in the near future.     

Chemical and biological differentiation of three human breast cancer cell types using time-of-flight secondary ion mass spectrometry

We use time-of-flight secondary ion mass spectrometry (TOF-SIMS) to image and classify individual cells on the basis of their characteristic mass spectra. Using statistical data reduction on the large data sets generated during TOF-SIMS analysis, similar biological materials can be differentiated on the basis of a combination of small changes in protein expression, metabolic activity and cell structure. We apply this powerful technique to image and differentiate three carcinoma-derived human breast cancer cell lines (MCF-7, T47D, and MDA-MB-231). In homogenized cells, we show the ability to differentiate the cell types as well as cellular compartments (cytosol, nuclear, and membrane). These studies illustrate the capacity of TOF-SIMS to characterize individual cells by chemical composition, which could ultimately be applied to detect and identify single aberrant cells within a normal cell population. Ultimately, we anticipate characterizing rare chemical changes that may provide clues to single cell progression within carcinogenic and metastatic pathways.     

Atorvastatin-loaded lipid nanoparticles: antitumor activity studies on MCF-7 breast cancer cells

Atorvastatin is a synthetic statin commonly used in the treatment of hypercholesterolemia. Apart from this, statins appear to have pleiotropic effects, including modulation of cell growth, apoptosis. Through modulation of these pathways, statins have the potential to influence a wide range of disease processes, including cancer. However, poor aqueous solubility (0.1?mg/mL) and poor oral bioavailability has limited therapeutic application of atorvastatin. Present work is an attempt to improve tumor targeting of atorvastatin by incorporating in nanostructured lipid carriers (NLCs) and studying its anticancer activity on MCF-7 cell lines. NLCs of atorvastatin were formulated by high-speed homogenization followed by probe sonication method. The optimized batch of NLCs had a mean size of 130.02?±?3.1?nm and entrapment efficiency of 90.42?±?3.7%. The in vitro drug release study by dialysis method indicated that drug entrapped in the NLCs remains entrapped at acidic pH as well as in phosphate buffer of pH 7.4 for a prolonged period of time as compared to plain drug. In vitro cytotoxicity studies on MCF-7 (mammary adenocarcinoma human cell lines) cell lines showed that concentration of drug required for total growth inhibition (TGI) and 50% growth inhibition (GI50) of MCF-7 cells was found to be 27.4?µg/mL and <10?µg/mL respectively, in case of atorvastatin- NLCs which is less than that required in case of plain atorvastatin and almost similar to that of adriamycin. All these findings reinforce the fact that atorvastatin loaded NLCs are promising novel delivery system for treating breast cancer.     

Formulation-optimization of solid lipid nanocarrier system of STAT3 inhibitor to improve its activity in triple negative breast cancer cells

In the present study, solid lipid nanoparticles (SLNs) have been formulated as a carrier system for effective intracellular delivery of STAT3 inhibitor, niclosamide (Niclo) to triple negative breast cancer (TNBC) cells. Emulsification-solvent evaporation method was employed in formulation of Niclo-loaded SLNs (Niclo-SLNs). The formula of Niclo-SLN was optimized by Box–Behnken design and characterized for their shape, size, and surface charge. The in vitro anti-cancer efficacy of Niclo-SLNs was studied in TNBC cells. The prepared Niclo-SLNs were found to be spherical with the particle size of 112.18?±?1.73?nm and zetapotential of 23.8?±?2.7?mV. In the in vitro anticancer study the Niclo SLNs show a better cytotoxicity than the naïve Niclo, which is attributed to improved cell uptake of SLN formulation. In conclusion, the results of the present study demonstrate that the formulation of Niclo as SLNs will improve the anticancer efficacy against TNBC.     

Preparation and optimization of monodisperse polymeric microparticles using modified vibrating orifice aerosol generator for controlled delivery of letrozole in breast cancer therapy

Abstract

Letrozole (LTZ) is effective for the treatment of hormone-receptor-positive breast cancer in postmenopausal women. In this work, and for the first time, using vibrating orifice aerosol generator (VOAG) technology, monodisperse poly-ε-caprolactone (PCL), and poly (D, L-Lactide) (PDLLA) LTZ-loaded microparticles were prepared and found to elicit selective high cytotoxicity against cancerous breast cells with no apparent toxicity on healthy cells in vitro. Plackett–Burman experimental design was utilized to identify the most significant factors affecting particle size distribution to optimize the prepared particles. The generated microparticles were characterized in terms of microscopic morphology, size, zeta potential, drug entrapment efficiency, and release profile over one-month period. Long-term cytotoxicity of the microparticles was also investigated using MCF-7 human breast cancer cell lines in comparison with primary mammary epithelial cells (MEC). The prepared polymeric particles were monodispersed, spherical, and apparently smooth, regardless of the polymer used or the loaded LTZ concentration. Particle size varied from 15.6 to 91.6?µm and from 22.7 to 99.6?µm with size distribution (expressed as span values) ranging from 0.22 to 1.24 and from 0.29 to 1.48 for PCL and PDLLA based microparticles, respectively. Upon optimizing the manufacture parameters, span was reduced to 0.162–0.195. Drug entrapment reached as high as 96.8%, and drug release from PDLLA and PCL followed a biphasic zero-order release using 5 or 30% w/w drug loading in the formulations. Long-term in vitro cytotoxicity studies indicated that microparticles formulations significantly inhibited the growth of MCF-7 cell line over a prolonged period of time but did not have toxic effects on the normal breast epithelial cells.     

Intracellular accumulation and cytotoxicity of doxorubicin with different pharmaceutical formulations in human cancer cell lines

The structure of both carrier and anticancer drug affects the intracellular fate of a transported drug. The study investigated in vitro intracellular accumulation and cytotoxic activity of doxorubicin-loaded solid lipid nanoparticles (SLN), doxorubicin in pegylated liposomes (Caelyx) and free doxorubicin. Intracellular doxorubicin levels and cytotoxic activity were determined by high performance liquid chromatography with fluorescence detection, and by the trypan blue dye exclusion assay, respectively. Doxorubicin-loaded SLN inhibited cell growth more strongly than either free or liposomal doxorubicin, in human colorectal adenocarcinoma, HT-29, retinoblastoma Y79, and glioblastoma U373 cell lines. The IC50 values for doxorubicin-loaded SLN were significantly lower after 24 h exposure than those for free doxorubicin in all cell lines; after 48 h exposure they were lower than those for liposomal doxorubicin in HT-29 and Y79 cells. The enhanced cytotoxic activity of doxorubicin-loaded SLN was associated with increased drug incorporation in cells: intracellular doxorubicin levels were significantly enhanced after exposure to drug-loaded SLN versus either free or liposomal drug. Rate of intracellular accumulation and cytotoxic activity also differed among different cell lines; in particular, cells of epithelial origin were found to be more sensitive to doxorubicin-loaded SLN. In conclusion, the greater sensitivity of HT-29, Y79, and U373 cells to doxorubicin-loaded SLN than to the other drug formulations may be due to the capability of the delivery system to enhance drug action, through a marked uptake and accumulation of SLN within the cell.     

Bioluminescence-based detection of microRNA, miR21 in breast cancer cells

A hybridization assay for the detection of microRNA, miR21 in cancer cells using the bioluminescent enzyme Renilla luciferase (Rluc) as a label, has been developed. MicroRNAs are small RNAs found in plants, animals, and humans that perform key functions in gene silencing and affect early-stage cell development, cell differentiation, and cell death. miRNAs are considered useful early diagnostic and prognostic markers of cancer, candidates for therapeutic intervention, and targets for basic biomedical research. However, methods for highly sensitive and rapid detection of miRNA directly from samples such as cells that can serve as a suitable diagnostics platform are lacking. In that regard, the utilization of the bioluminescent label, Rluc, that offers the advantage of high signal-to-noise ratio, allows for the development of highly sensitive assays for the determination of miRNA in a variety of matrixes. In this paper, we have described the development of a competitive oligonucleotide hybridization assay for the detection of miR21 using the free miR21 and Rluc-labeled miR21 that competes to bind to an immobilized miR21 complementary probe. The miR21 microRNA chosen for this study is of biomedical significance because its levels are elevated in a variety of cancers. Using the optimized assay, a detection limit of 1 fmol was obtained. The assay was employed for the detection of miR21 in human breast adenocarcinoma MCF-7 cells and nontumorigenic epithelial MCF-10A cells. The comparison of miR21 expression level in two cell lines demonstrated higher expression of miR21 in breast cancer cell line MCF-7 compared to the nontumorigenic MCF-10A cells. Further, using the assay developed, the miR21 quantification could be performed directly in cell extracts. The hybridization assay was developed in a microplate format with a total assay time of 1.5 h and without the need for sample PCR amplification. The need for early molecular markers and their detection methods in cancer diagnosis is tremendous. The characteristics of the assay developed in this work show its suitability for early cancer diagnosis based on miRNA as a biomarker.     

Overcoming multidrug resistance of breast cancer cells by the micellar doxorubicin nanoparticles of mPEG-PCL-graft-cellulose

The amphiphilic block copolymer methoxy-poly(ethylene glycol)-poly(epsilon-caprolactone) (mPEG-PCL) was grafted to 2-hydroxyethyl cellulose (HEC) to produce nano-sized micellar nanoparticles. The nanoparticles were loaded with anti-tumor drug, doxorubicin (DOX) and the size of the DOX-loaded nanoparticles were determined by dynamic light scattering (DLS) in aqueous solution to be from 197.4 to 230 nm. The nanoparticles subjected to co-culture with macrophage cells showed that these nanoparticles used as drug carrier are not recognized as foreign bodies. Overexpression of P-glycoprotein (P-gp) is an important factor in the development of multidrug resistance (MDR) in many cancer cells. In this study, Western blot and Rhodamine 123 were used to monitor the relative P-glycoprotein expression in human breast cancer cell lines MCF-7/WT and MCF-7/ADR. The endocytosis of the DOX-loaded nanoparticles by breast cancer cells is more efficient observed under a confocal laser scanning microscopy (CLSM) and a flow cytometry in MCF7/ADR cells, compared to the diffusion of the free drug into the cytoplasm of cells. Based on these findings, we concluded that the nanoparticles made from mPEG-PCL-g-cellulose were effective in overcoming P-gp efflux in MDR breast cancer cells.     

Green synthesis of silver nanoparticles using Rubia tinctorum extract and evaluation the anti‐cancer properties in vitro

Cancer is one of the leading causes of human death. Nanotechnology could offer new and optimised anticancer agents in order to fight cancer. It was shown that metal nanoparticles, in particular silver nanoparticles (AgNPs) were effective in cancer therapy. In this study, AgNPs were synthesised using Rubia tinctorum L. extract (Ru‐AgNPs). Then, cytotoxicity effects of the Ru‐AgNPs against MDA‐MB‐231 carcinoma cell line and human dermal fibroblast as normal cell line were performed. Furthermore, anti‐apoptotic effects of Ru‐AgNPs on these cancer and normal cell lines were compared using acridine orange/propidium iodide staining, flow cytometry analysis and real‐time qPCR in apoptosis gene markers. Results of UV‐vis spectroscopy showed that Ru‐AgNPs have a peak at 430 nm, which indicated synthesis of AgNPs. Ru‐AgNPs had spherical shape and average size of 12 nm. Ru‐AgNPs have cytotoxicity on MDA‐MB‐231 cells and decrease cancerous cell viability (IC50 = 4 µg/ml/48 h). Ru‐AgNPs could induce apoptosis in MDA‐MB‐231 cells through upregulation of Bax and downregulation of Bcl‐2 gene expression. The results opened up new avenues to develop Rubia based metal complexes as an anticancer agent.Inspec keywords: cellular biophysics, genetics, cancer, toxicology, nanoparticles, nanofabrication, nanomedicine, silver, biomedical materials, ultraviolet spectra, visible spectraOther keywords: Ru‐AgNPs, MDA‐MB‐231 carcinoma cell line, normal cell line, cancerous cell viability, in vitro anticancer properties, green synthesis, silver nanoparticles, Rubia tinctorum L. extract, cytotoxicity effects, human dermal fibroblast HFF, antiapoptotic effects, acridine orange‐propidium iodide staining, flow cytometry analysis, real‐time qPCR, apoptosis gene markers, UV‐visible spectroscopy, spherical shape, Bcl‐2 gene expression, Ag     

Gold nano-popcorn attached SWCNT hybrid nanomaterial for targeted diagnosis and photothermal therapy of human breast cancer cells

Breast cancer presents greatest challenge in health care in today's world. The key to ultimately successful treatment of breast cancer disease is an early and accurate diagnosis. Current breast cancer treatments are often associated with severe side effects. Driven by the need, we report the design of novel hybrid nanomaterial using gold nano popcorn-attached single wall carbon nanotube for targeted diagnosis and selective photothermal treatment. Targeted SK-BR-3 human breast cancer cell sensing have been performed in 10 cancer cells/mL level, using surface enhanced Raman scattering of single walls carbon nanotube's D and G bands. Our data show that S6 aptamer attached hybrid nanomaterial based SERS assay is highly sensitive to targeted human breast cancer SK-BR-3 cell line and it will be able to distinguish it from other non targeted MDA-MB breast cancer cell line and HaCaT normal skin cell line. Our results also show that 10 min of photothermal therapy treatment by 1.5 W/cm(2) power, 785 nm laser is enough to kill cancer cells very effectively using S6 aptamer attached hybrid nanomaterials. Possible mechanisms for targeted sensing and operating principle for highly efficient photothermal therapy have been discussed. Our experimental results reported here open up a new possibility for using aptamers modified hybrid nanomaterial for reliable diagnosis and targeted therapy of cancer cell lines quickly.     

Augmented anticancer activity of naringenin-loaded TPGS polymeric nanosuspension for drug resistive MCF-7 human breast cancer cells

Naringenin (NAR) is a naturally occurring plant flavonoid, found predominantly in citrus fruits, possesses a wide range of pharmacological properties. However, despite the therapeutic potential of NAR, its clinical development has been hindered due to low aqueous solubility and inefficient transport across biological membranes resulting in low bioavailability at tumor sites. In our previous studies, nanosuspension of naringenin (NARNS) was prepared using high pressure homogenization method using different polymers. D-α-Tocopheryl polyethylene glycol succinate 1000 (TPGS) was added as a co-stabilizer. All formulation characterization studies were performed. As a continuation of our previous research, current study has further evaluated the ability of the TPGS-coated NARNS, to reverse drug-resistance of P-gp-over expressing MCF-7 human breast adenocarcinoma cell line and animal model. MTT-based colorimetric assay revealed higher cytotoxic efficacy of NARNS than free NAR in MCF-7 cells. NARNS treatment significantly increased intracellular ROS level, mitochondrial membrane potential, caspase-3 activity, lipid peroxidation status (TBARS) and decreased GSH levels when compared to free NAR treatment in MCF-7 cells. It has been also noticed that the presence of apoptotic indices (membrane blebbing, nuclear fragmentation) in NARNS treated cancer cells. Further, NARNS exhibited dose-dependent in vitro antitumor activity with DLA cells. A significant increase in the life span and a decrease in the cancer cell number and tumor weight were noted in the tumor-induced mice after treatment with NARNS.     

Soluplus/TPGS mixed micelles for dioscin delivery in cancer therapy

Background: Dioscin has shown cytotoxicity against cancer cells, but its poor solubility and stability have limited its clinical application. In this study, we designed mixed micelles composed of TPGS and Soluplus^® copolymers entrapping the poorly soluble anticancer drug dioscin.

Method: In order to improve the aqueous solubility and bioactivity of dioscin, TPGS/Soluplus^® mixed micelles with an optimal ratio were prepared using a thin-film hydration method, and their physicochemical properties were characterized. Cellular cytotoxicity and uptake of the dioscin-loaded TPGS/Soluplus^® mixed micelles were studied in MCF-7 breast cancer cells and A2780s ovarian cancer cells. The pharmacokinetics of free dioscin and dioscin-loaded TPGS/Soluplus^® mixed micelles was studied in vivo in male Sprague-Dawley rats via a single intravenous injection in the tail vein.

Results: The average size of the optimized mixed micelle was 67.15?nm, with 92.59% drug encapsulation efficiency and 4.63% drug loading efficiency. The in vitro release profile showed that the mixed micelles presented sustained release behavior compared to the anhydrous ethanol solution of dioscin. In vitro cytotoxicity assays were conducted on human cancer cell lines including A2780s ovarian cancer cells and MCF-7 breast cancer cells. The mixed micelles exhibited better antitumor activity compared to free dioscin against all cell lines, which may benefit from the significant increase in the cellular uptake of dioscin from mixed micelles compared to free dioscin. The pharmacokinetic study showed that the mixed micelle formulation achieved a 1.3 times longer mean residual time (MRT) in circulation and a 2.16 times larger area under the plasma concentration–time curve (AUC) than the free dioscin solution.

Conclusion: Our results suggest that the dioscin-loaded mixed micelles developed in this study might be a potential nano drug-delivery system for cancer chemotherapy.     

Synthesis and Characterization of Carboxylated Luteolin (CL)-Functionalized SPION

In this study, a stable carboxylated luteolin (CL)-functionalized superparamagnetic iron oxide nanoparticle (SPION) as a potential drug carrier for in vitro analysis of L929 (mouse fibroblast), U87 (glioblastoma (brain cancer)), MCF-7 (breast cancer), HeLa (cervix cancer), and A549 (human lung cancer) cell lines has been synthesized. Thermal decomposition and Stöber methods were used to prepare 3-aminopropyl triethoxysilane-capped SPIONs respectively. Carboxylated polyethylene glycol (PEG-COOH), folic acid (FA), and CL were conjugated on the surface via a carboxylic/amine group using the nanoprecipitation method respectively. Internalization of CL-functionalized SPION and the release of luteolin from it has been studied using Prussian blue staining and spectrophotometry respectively. The cytotoxicity of CL-functionalized SPION on cell lines was tested by MTT assay. Internalization of product by HeLa, MCF-7, and U87 was higher than A549 and L929 cells. It was observed that luteolin release increased in an acidic environment (pH 5.4). A newly synthesized SPION-FA-PEG in all concentrations (except 500 μg/mL) did not show notable toxicity against L929, U87, MCF-7, HeLa, and A549. However, the product in all used concentrations decreased cell viability at the 24th and 48th hours. This study confirmed that the product has a potential to be used as an anti-cancer CL-functionalized SPION for targeted drug delivery.