Michigan Cancer Foundation-7 Cells Research Articles

Antiproliferative activity and nitric oxide production of a methanolic extract of Fraxinus micrantha on Michigan Cancer Foundation-7 mammalian breast carcinoma cell line.

Aim:Methanolic extract of a Fraxinus micrantha (MeFM) was evaluated for antiproliferative activity in vitro using Michigan Cancer Foundation-7 (MCF-7) breast carcinoma cell line. This plant was selected and studied for naturally available bioactive compound as different synthetic drugs available for cancer treatment has certain limitations and side effects.Materials and Methods:The anti-proliferative activity of a methanolic extract from the aerial parts of F. micrantha was assessed on MCF-7 breast cancer cell line using 3(4,5-dimethylthiazol-2-yl)2,5-diphenyl-tetrazolium bromide assay. Furthermore, to understand the mechanism of anti-proliferation, production of nitric oxide (NO) and DNA fragmentation was also determined on MCF-7 cells. Different phytoconstituents of the extract were determined qualitatively based on various biochemical assays.Results:The results demonstrated anti-proliferative activity of an MeFM in a concentration and time-dependent manner. The percentage viability determined was 31.24% at 125 µg/ml as compared to 80.46% in negative control group. An MeFM has also shown NO production in a concentration (0.2-125 µg/ml) and time-dependent manner (24-48 h). DNA fragmentation studies showed that a methanolic extract was causing DNA fragmentation thus inducing apoptosis in MCF-7 breast carcinoma cells. Biochemical analysis result showed the presence of flavonoids, polyphenols, and sterols in an MeFM.Conclusion:In conclusion, F. micrantha possesses potent anti-proliferative activity on the malignant MCF-7 cell line which is correlated with the production of NO and DNA fragmentation. Further studies are required to identify, isolate, and characterize the phytochemicals present in the methanolic extract that might have antiproliferative potential in the treatment of different cancer conditions.

Fabrication of Microenvironments with Different Geometrical Features for Cell Growth Studies

Studies of cell development in artificial microenvironments can contribute to understanding a series of physiological mechanisms that might be influenced by geometrical features of the microenvironment itself. In this work we applied two-photon polymerization to fabricate threedimensional microenvironments composed of a matrix arrangement of microstructures (circular and square cross-sections pillars) with distinct spacing. Such microenvironments were used to evaluate the growth of Michigan Cancer Foundation-7 (MCF-7) cells that are commonly used as a model system to investigate fundamental aspects of the tumor biology. Our results reveal that the cell density decreases as the distance between structures in the environment is increased. Additionally, cell growth shows slightly better results for the microenvironments composed of circular crosssection structures.

Isoflavones extracted from chickpea Cicer arietinum L. sprouts induce mitochondria-dependent apoptosis in human breast cancer cells.

Isoflavones are important chemical components of the seeds and sprouts of chickpeas. We systematically investigated the effects of isoflavones extracted from chickpea sprouts (ICS) on the human breast cancer cell lines SKBr3 and Michigan Cancer Foundation-7 (MCF-7). 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays showed that ICS (10-60 µg/mL) significantly inhibited the proliferation of both cell lines in a time-dependent and dose-dependent fashion. Wright-Giemsa staining as well as annexin V-fluorescein isothiocyanate and propidium iodide (Annexin V/PI) staining showed that ICS significantly increased cytoclasis and apoptotic body formation. Quantitative Annexin V/PI assays further showed that the number of apoptotic cells increased in a dose-dependent manner following ICS treatment. Semiquantitative reverse transcription PCR showed that ICS increased the expression of the apoptosis-promoting gene Bcl-2-associated X protein and decreased the expression of the antiapoptotic gene Bcl-2. Western blot analysis showed that treatment of SKBr3 and MCF-7 cells with ICS increased the expression of caspase 7, caspase 9, P53, and P21 in a dose-dependent manner. Flow cytometry assays using the fluorescent probe 3,3'-dihexyloxacarbocyanine iodide showed a dose-dependent decrease in mitochondrial membrane potential following ICS treatment. Treatment using ICS also induced a dose-dependent increase in reactive oxygen species production. This is the first study to demonstrate that ICS may be a chemopreventive or therapeutic agent against breast cancer.

Effects of Flos Sophorae Ethanol Extract on NF-kB Dependent MMP-9 Expression in Human Breast Cancer Cell

Flos Sophorae, the dried flower bud of Sophora japonica L, possesses anti-inflammatory properties, prevents and treats blood capillary and hypertension diseases and can also be used as a hemostat. However, the effect of Flos Sophorae on breast cancer invasion is unknown. Matrix metalloproteinase-9 (MMP-9), which degrades the extracellular matrix, is a major component in cancer cell invasion. In this study, we investigated the inhibitory effect of Flos Sophorae extract (FSE) on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced Matrix metalloproteinase-9 (MMP-9) expression and cell invasion, as well as the molecular mechanisms involved in Michigan Cancer Foundation-7 (MCF-7) cells. FSE inhibited the TPA-induced transcriptional activation of nuclear factor-kappa B (NF-κB). These results indicate that FSE-mediated inhibition of TPA-induced MMP-9 expression and cell invasion involves the suppression of NF-kB pathway in MCF-7 cells. Thus, FSE may have therapeutic potential for controlling breast cancer invasiveness. 

The Effects of Olive Leaf Extract on Antioxidant Enzymes Activity and Tumor Growth in Breast Cancer

Background: Recently, it is suggested that the use of olive leaf polyphenols like oleuropein (OLP), hydroxytyrosol (HT), and others could decrease breast cancer cells viability significantly. Also it has been shown that it inhibits cell proliferation, induces cell apoptosis, reduces cell viability, and significantly stops cell cycle in growth 1 phase (G1) demonstrated via increasing the Michigan Cancer Foundation-7 (MCF-7) cells in the G0/G1 phase. Objectives: We aimed to study whether the use of olive leaf extract affects breast tumor size and the activity of antioxidant enzymes. Materials and Methods: Four groups of female BALB/c, each containing five mice were studied. Three days after tumor transplantation, the first group received distilled water. The second, third, and fourth groups were treated with 75, 150, and 225 mg/kg/day of olive leaf extract (OLE) for 3 weeks, respectively. To assess anti-cancer and antioxidant effect of OLE, volume and weight of tumor, and also antioxidant enzyme activity were measured. Results: Treatment with 150 and 225 mg/kg/day of OLE reduced the tumor volume and weight (P < 0.05) compared to the first group significantly. It also increased the CAT activity (P < 0.05) in the third group and increased the activity of superoxide dismutase in the third (P < 0.05) and fourth groups (P < 0.005) resulted in excitotoxic tolerance in the treatment groups. Conclusions: Consumption of OLE after tumor transplantation reduced the tumor growth. On the other hand, owing to its highly-packed polyphenols, catalase and superoxide dismutase activities in tumor tissue were increased.

In-silico design, synthesis and biological evaluation of 4-aryl-4H-chromene derivatives as CDK-2 inhibitors: A molecular approach to finding a lead for breast cancer

Breast cancer is a major health concern, with a mortality rate worldwide. Targeted therapy has emerged as a promising option for cancer treatment, particularly through the inhibition of cyclin-dependent kinase-2 (CDK-2), holding a promise for combating this disease. The potential of 4-aryl-4H-chromene derivatives as inhibitors of CDK- 2 was evaluated in this study using the in silico method. Amongst the 38 designed compounds, 13 compounds were identified as potential CDK-2 inhibitors based on their superiority within in silico studies with docking scores ranging from −9.180 to −8.006 Kcal/mol and with favourable absorption, distribution, metabolism, excretion, and toxicity properties. These 13 compounds were later synthesized and characterized using spectral methods. Furthermore, these compounds were assessed for their antioxidant and anticancer properties by in vitro assays. Compounds 2M and 2C displayed notable antioxidant potential with IC50 values of 24.44 and 39.03 μM, respectively, in 2,2-Diphenyl- 1-picrylhydrazyl and 2,2′-casino-bis (3-ethylbenzothiazoline-6-sulfonic acid) assays. The sulforhodamine B assay on Michigan Cancer Foundation-7 (MCF-7) cells indicated that compound 1L demonstrated the strongest growth inhibition activity with an IC50 of 0.2 μM. Five other compounds (2O, 2K, 1C, 2M, and 2J) also exhibited promising activity with IC50 values ranging from 11.74 to 27.2 μM. In conclusion, 4-aryl-4H-chromene derivatives can be considered potential lead candidates for breast cancer treatment.

Investigating the antioxidant and anticytotoxic activities of propolis collected from five regions of Indonesia and their abilities to induce apoptosis

Propolis is a resinous substance collected by stingless bee or honey bee from various plant sources. The substance is known to contain beneficial properties for human. The geographical origin of propolis determines its biological properties. In this study, propolis were collected from five regions of Indonesia with the objective of determining the yield, their total flavonoid content, their capacity to induce apoptosis, and their toxicity to the Michigan Cancer Foundation-7 (MCF-7) cell line. The inhibition of antioxidant 1,1-diphenyl-2-picrylhydrazyl (DPPH), the induction of apoptosis to Saccharomyces cerevisiae and the anticytotoxic ability were determined. Propolis from Pekanbaru region had higher yield than other regions with value of 19.97%; propolis from Kendal had higher quantity with value of 46.60%, total flavonoid content; propolis from Pandeglang was higher in DPPH oxidation capacity with value of 68.94 ?g.ml-1; propolis from Kendal, expressed petite cell induction in S. cerevisiae cells with value of 81.44%, and the anticytotoxic to MCF-7 breast cancer cell line were best observed in propolis from Makassar region with a value of 47.71% life cells. All of the propolis extracted from the stingless bee hive Trigona spp from five regions in Indonesia contained flavonoids.

Self-assembled pH-responsive hyaluronic acid–g-poly(l-histidine) copolymer micelles for targeted intracellular delivery of doxorubicin

Hyaluronic acid (HA) was conjugated with hydrophobic poly(l-histidine) (PHis) to prepare a pH-responsive and tumor-targeted copolymer, hyaluronic acid–g-poly(l-histidine) (HA-PHis), for use as a carrier for anti-cancer drugs. The effect of the degree of substitution (DS) on the pH-responsive behaviour of HA-PHis copolymer micelles was confirmed by studies of particles of different sizes. In vitro drug release studies demonstrated that doxorubicin (DOX) was released from HA-PHis micelles in a pH-dependent manner. In vitro cytotoxicity assays showed that all the blank micelles were nontoxic. However, MTT assay against Michigan Cancer Foundation-7 (MCF-7) cells (overexpressed CD44 receptors) showed that DOX-loaded micelles with a low PHis DS were highly cytotoxic. Cellular uptake experiments revealed that these pH-responsive HA-PHis micelles taken up in great amounts by receptor-mediated endocytosis and DOX were efficiently delivered into cytosol. Moreover, micelles with the lowest DS exhibited the highest degree of cellular uptake, which indicated that the micelles were internalized into cells via CD44 receptor-mediated endocytosis and the carboxylic groups of HA are the active binding sites for CD44 receptors. Endocytosis inhibition experiments and confocal images demonstrated that HA-PHis micelles were internalized into cells mainly via clathrin-mediated endocytosis and delivered to lysosomes, triggering release of DOX into the cytoplasm. These results confirm that the biocompatible pH-responsive HA-PHis micelles are a promising nanosystem for the intracellular targeted delivery of DOX.

Design, Synthesis, and Anticancer Properties of Novel Benzophenone‐Conjugated Coumarin Analogs

In the current scenario, development of anticancer drugs with specific targets is of prime importance in modern chemical biology. Observing the importance of benzophenone and coumarin nucleus, it would be worthwhile to design and synthesize novel benzophenone derivatives (8a-o) bearing the coumarin nucleus. Further, they were screened for prospective anticancer activities in vitro against the Michigan Cancer Foundation-7 (MCF-7) and Ehrlich's ascites tumor (EAT) cell lines and their biomarkers, followed by in silico studies regarding phosphoinositide 3-kinase (PI3K) and caspase by molecular docking. Benzophenones have been reported as potential drugs targeting tumor angiogenesis; thus, the formation of neovessels in an in vivo model system like CAM, which is angiogenesis dependent, was observed in the presence of compounds 8a-o. The above findings would help in understanding their putative potential as therapeutic agents for cancer patients.

Preparation of 17β-estradiol surface molecularly imprinted polymers and their application to the analysis of biological samples

17β-Estradiol (E2) surface molecularly imprinted polymers have been prepared using functionalized monodispersed poly(glycidyl methacrylate-co-ethylene dimethacrylate) beads as a support. The resulting polymers were found to be uniform in size (5 μm), and the surfaces of the microspheres possessed large pore-like structures. A chromatographic experiment demonstrated that the resulting microspheres exhibited high levels of recognition and selectivity toward the target molecule. The particles were employed as a novel sorbent in a molecularly imprinted SPE protocol. A method was then developed involving the combination of the pretreatment with HPLC to determine the levels of estrogen secreted from Michigan Cancer Foundation-7 cells. The obtained results revealed that the extraction recoveries of E2 from real samples were in the range of 73.0-97.5% with RSDs of < 7.5% (n = 3). Calibration curves were established with R values > 0.9996 for concentrations in the range of 0.50-100.00 ng/mL. The LOD of this new method was 0.14 ng/mL. Compared with traditional C18 SPE agents, the particles showed high selectivity and extraction efficiency for E2 in the pretreatment process. The particles could therefore be used to determine trace estrogen in biological samples with a UV detector only.

Label-free detection of anticancer drug paclitaxel in living cells by confocal Raman microscopy

Confocal Raman microscopy, a non-invasive, label-free, and high spatial resolution imaging technique is employed to trace the anticancer drug paclitaxel in living Michigan Cancer Foundation-7 (MCF-7) cells. The Raman images were treated by K-mean cluster analysis to detect the drug in cells. Distribution of paclitaxel in cells is verified by calculating the correlation coefficient between the reference spectrum of the drug and the whole Raman image spectra. A time dependent gradual diffusion of paclitaxel all over the cell is observed suggesting a complementary picture of the pharmaceutical action of this drug based on rapid binding of free tubulin to crystallized paclitaxel.

Cell specific cytotoxicity and uptake of graphene nanoribbons

The synthesis of oxidized graphene nanoribbons (O-GNR) via longitudinal unzipping of carbon nanotubes opens avenues for their further development for a variety of biomedical applications. Evaluation of the cyto- and bio-compatibility is necessary to develop any new material for in vivo biomedical applications. In this study, we report the cytotoxicity screening of O-GNRs water-solubilized with PEG-DSPE (1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)]), using six different assays, in four representative cell lines; Henrietta Lacks cells (HeLa) derived from cervical cancer tissue, National Institute of Health 3T3 mouse fibroblast cells (NIH-3T3), Sloan Kettering breast cancer cells (SKBR3) and Michigan cancer foundation-7 breast cancer cells (MCF7). These cell lines significantly differed in their response to O-GNR-PEG-DSPE formulations; assessed and evaluated using various endpoints (lactate dehydrogenase (LDH) release, cellular metabolism, lysosomal integrity and cell proliferation) for cytotoxicity. In general, all the cells showed a dose-dependent (10–400 μg/ml) and time-dependent (12–48 h) decrease in cell viability. However, the degree of cytotoxicity was significantly lower in MCF7 or SKBR3 cells compared to HeLa cells. These cells were 100% viable upto 48 h, when incubated at 10 μg/ml O-GNR-PEG-DSPE concentration, and showed decrease in cell viability above this concentration with ∼78% of cells viable at the highest concentration (400 μg/ml). In contrast, significant cell death (5–25% cell death depending on the time point, and the assay) was observed for HeLa cells even at a low concentration of 10 μg/ml. The decrease in cell viability was steep with increase in concentration with the CD50 values ≥ 100 μg/ml depending on the assay, and time point. Transmission electron microscopy of the various cells treated with the O-GNR solutions show higher uptake of the O-GNR-PEG-DSPEs into HeLa cells compared to other cell types. Additional analysis indicates that this increased uptake is the dominant cause of the significantly higher toxicity exhibited by HeLa cells. The results suggest that water-solubilized O-GNR-PEG-DSPEs have a heterogenous cell-specific cytotoxicity, and have significantly different cytotoxicity profile compared to graphene nanoparticles prepared by the modified Hummer's method (graphene nanoparticles prepared by oxidation of graphite, and its mechanical exfoliation) or its variations.

Dynamic behaviors of vimentin induced by interaction with GlcNAc molecules

The cytoskeleton protein vimentin is dramatically altered following pathological events such as fibrosis and tumorigenesis. Vimentin binds to multivalent N-acetylglucosamine (GlcNAc) molecules at the cell surface and interacts with O-linked β-GlcNAc proteins. Moreover, dying cells can be engulfed by neighboring cells through surface interactions between vimentin and many O-GlcNAc proteins in cell debris. Here, we show that vimentin was altered by its interaction with GlcNAc-bearing molecules such as GlcNAc-bearing polymers. The interaction with GlcNAc-bearing polymers promoted the cell surface recruitment of vimentin followed by the phosphorylation of vimentin serine 71 and the increase in tetrameric vimentin disassembled from vimentin filaments in HeLa cells. Moreover, it was found that GlcNAc-bearing polymers and O-GlcNAc proteins from dying cells promoted vimentin expression and cell migration in the Madin-Darby canine kidney and Michigan Cancer Foundation-7 cells. These results suggest that interactions between surface vimentin and GlcNAc molecules, including the O-GlcNAc proteins from dying cells, may play a pivotal role in vimentin expression and the migration of cancer cells. We propose new mechanisms of vimentin expression in cancer cells.

In vitro screening of dry fruit extracts of Piper attenuatum for antioxidant and anticancer activity

Indian traditional medicinal plant Piper attenuatum (Buch-Ham) has been investigated for its antioxidant and anticancer activity. Three extracts were prepared using ethyl acetate, ethanol and methanol. In vitro antioxidant activity was performed by ABTS {2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid)} free radical scavenging method. All three extracts reduced the free radicals produced by ABTS in a concentration-dependent manner which could be compared to the standard (gallic acid). Invitro anticancer activity of all extracts was carried out by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay method against MCF7 (Michigan Cancer Foundation-7) cell lines. None of the extract showed anticancer activity when compared with the standard (mitomycin C) indicating that P. attenuatum is deprived of antiproliferative or cytotoxic components.

Preparation and cytotoxicity of 2-methoxyestradiol-loaded solid lipid nanoparticles

The objective of this study was to prepare 2-methoxyestradiol (2-ME)-loaded solid lipid nanoparticles (SLN) by hot homogenization-ultrasonication and evaluate their cytotoxicity on three cell lines, breast cancer [Michigan Cancer Foundation-7 (MCF-7)], prostatic carcinoma (PC-3), and glioma (SK-N-SH), by the sulforhodamineB method. The particle sizes and zeta potentials of the prepared SLN were around 120 nm and -40 mV, respectively. Differential scanning calorimetry (DSC) measurements revealed that the monostearin and 2-ME existed in solid and amorphous states in the SLN prepared, respectively. The high drug entrapment efficiency (>85%) indicated that most 2-ME was incorporated in the SLN. An in-vitro drug release study showed that 2-ME was released from the SLN in a slow but time-dependent manner. The cytotoxicity of 2-ME in SLN on each cell line was significantly enhanced compared with the solution. 2-ME SLN composed of Tween80 was approximately 17-fold more effective on PC-3 cells and 6.7-fold more effective on SK-N-SH cells than in the solution, whereas a lower sensitivity was achieved on MCF-7 cells. In each cell line, the cellular uptake percentages of 2-ME in SLN were much higher than the solution, respectively. In addition, surfactants may exert different effects on the cytotoxicity of 2-ME SLN depending on the cell line. The above assay demonstrated that SLN could significantly enhance the cytotoxicity of 2-ME compared with the free drug because of the increased cellular internalization and concentration of 2-ME. The results suggested that SLN could be an excellent carrier candidate to entrap 2-ME for improving the effectiveness of tumor chemotherapy.

The study of anticancer and antifungal activities of Pistacia integerrima extract In vitro

Pistacia integerrima Stew. ex Brand (Anacardiaceae) is an ethanobotanically important plant species traditionally used in the treatment of chronic wounds, jaundice, dysentery, etc. The crude extract from Pistacia integerrima and its fractions were tested for cytotoxic activity against Michigan Cancer Foundation-7 human breast cancer cell line. We have also investigated that crude stem extract of this plant also exhibits the antitumour as well as antifungal potential activities. Moreover, we have also studied that the crude extract inhibited Michigan Cancer Foundation-7 cell viability in a dose-dependent manner; the poor toxicity (1.6%) at 10 μg/ml to moderate toxicity (55.4%) at 100 μg/ml. The IC50 values calculated were 90.9 μg/ml. The ethyl acetate and chloroform fractions at a concentration of 200 μg/ml showed ~100 and 97.4% inhibition against Michigan Cancer Foundation-7 cell line, respectively. The crude methanol extract also showed good antitumour (IC50 125 ppm) activity, but weak antifungal activity. These findings reveal that the ethyl acetate and chloroform fractions of Pistacia integerrima are potent cytotoxic fractions, and could be an alternate candidate for the development of novel biologically active compounds.

Antiproliferative activity of nanofibers containing quaternized chitosan and/or doxorubicin against MCF-7 human breast carcinoma cell line by apoptosis

The antiproliferative activity of electrospun mats of poly(L-lactide- co-D,L-lactide) (coPLA) containing quaternized chitosan (QCh) and/or doxorubicin hydrochloride (DOX) was evaluated against the Michigan Cancer Foundation-7(MCF-7) human breast carcinoma cell line. QCh- and DOX-containing nanofibrous mats possess good antiproliferative activity and decrease considerably the viability of the MCF-7 cells for the different periods of cell incubation as confirmed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Fluorescent microscopy analyses and scanning electron microscopy observations revealed that apoptosis was one of the major mechanisms of MCF-7 cell death induced by the QCh- and DOX-containing mats.

Effect of flavonone hesperidin on the apoptosis of human mammary carcinoma cell line MCF-7

The aim of the present study was to investigate the impact of a natural citrus flavonoglycoside hesperidin on the human mammary carcinoma cell line (MCF-7) and its possible role in the induction of apoptosis. Human breast cancer cells were treated with different concentrations of hesperidin and its cytotoxicity effect was measured by MTT method and lactate dehydrogenase leakage assays. Apoptosis was analyzed by light microscopic studies and DNA fragmentation. The mechanism of apoptosis was studied with the expression of p53 and caspase-3 proteins. Glutathione content was also measured in MCF-7 cells after hesperidin treatment. The results revealed that hesperidin significantly inhibited the proliferation of MCF-7 cells in a concentration-dependent manner. Apoptotic morphology was observed in MCF-7 cells treated with hesperidin at the concentration of 60 and 80 μM. DNA fragmentation, accumulation of p53 and expression of caspase-3 proteins were observed in MCF-7 cells after the treatment with hesperidin. The depletion of GSH and an elevation of LDH were observed in MCF-7 cells treated with hesperidin. Therefore in conclusion, hesperidin induced cytotoxicity in MCF-7 cells in vitro. Apoptosis of MCF-7 cells may be due to the DNA damage and expression of apoptotic proteins. Depletion of GSH may be involved in the induction of apoptosis of Michigan cancer foundation-7 cells.

Enhanced cellular uptake of folic acid–conjugated PLGA–PEG nanoparticles loaded with vincristine sulfate in human breast cancer

The aim of this paper is to evaluate the cellular uptake of vincristine sulfate-loaded poly(lactic-co-glycolic acid)–polyethylene glycol (PLGA–PEG) nanoparticles with the folic acid modification (PLGA–PEG–folate NPs). PLGA–PEG–folate NPs were prepared using a water–oil–water emulsion solvent evaporation method. The particle size, surface morphology, drug encapsulation efficiency, and the drug release behavior were investigated. The NPs exhibited a biphasic drug release with a moderate initial burst followed by a sustained release profile. Internalization of the NPs labeled with coumarin- 6 by MCF-7 (Michigan Cancer Foundation-7) human breast cancer cells was quantitatively measured by microplate reader, and qualitatively analyzed by fluorescent microscopy and confocal laser scanning microscopy. The results showed PLGA–PEG–folate NPs achieved significantly higher cellular uptake in the folic acid receptor overexpressed MCF-7 cells, compared to PLGA–mPEG NPs without the folic acid modification. Due to the enhanced cellular uptake, PLGA–PEG–folate NPs displayed the highest cytotoxicity. Judged by IC50 after 24 h culture, the therapeutic effects of the drug formulated in the NPs with surface modification could be 1.52 times, 3.91 times higher than that of PLGA–mPEG NPs and free vincristine sulfate, respectively.

Optimization of Landscape Phage Fusion Protein-Modified Polymeric PEG-PE Micelles for Improved Breast Cancer Cell Targeting.

Amphiphilic landscape phage fusion proteins with high affinity and selectivity towards breast cancer MCF-7 (Michigan Cancer Foundation-7) cells self-assemble with polymeric PEG-PE conjugates to form mixed micelles (phage-micelles) capable of cancer cell-targeted delivery of poorly-soluble drugs. While the PEG corona provides the stability and longevity to the micelles, its presence is a potential steric difficulties for the interaction of phage fusion protein with cell surface targets. We attempted to address this problem by controlling the length of the PEG block and the phage fusion protein quantity, selecting the optimal ones to produce a reasonable retention of the targeting affinity and selectivity of the MCF-7-specific phage fusion protein. Three PEG-PE conjugates with different PEG lengths were used to construct phage- and plain-micelles, followed by FACS analysis of the effect of the PEG length on their binding affinity and selectivity towards target MCF-7 cells using either a MCF-7 cell monoculture or a cell co-culture model composed of target cancer MCF-7 cells and non-target, non-cancer C166 cells expressing GFP (Green Fluorescent Protein). Both, the length of PEG and quantity of phage fusion protein had a profound impact on the targetability of the phage-micelles. Phage-micelles prepared with PEG2k-PE achieved a desirable binding affinity and selectivity. Incorporation of a minimal concentration of phage protein, up to 0.5%, produced maximal targeting efficiency towards MCF-7 cells. Overall, phage-micelles with PEG2k-PE and 0.5% of phage protein represent the optimal formulation for targeting towards breast cancer cells.