SPION@APTES@FA-PEG@Usnic Acid Bionanodrug for Cancer Therapy

In this work, we aimed to develop stable usnic acid (UA)-conjugated superparamagnetic iron oxide nanoparticles (SPIONs) as a potential drug carrier for in vitro analysis of MCF-7 (breast cancer cell line), HeLa (cervix cancer cell line), L929 (mouse fibroblast cell line), U87 (glioblastoma cell line, brain cancer), and A549 (human lung cancer cell line) cell lines. SPIONs were synthesized via the polyol method and functionalized with APTES using the Stöber method. Carboxylated polyethylene glycol (PEG-COOH), folic acid (FA), and carboxylated luteolin (CL) were conjugated on the surface via a carboxylic/amine group using the nanoprecipitation method, respectively. X-ray powder diffraction analysis confirmed the purity of the product with crystallite size of around 11 nm. Fourier-transformed infrared spectrophotometer (FT-IR) analyses explained the conjugation of all functional groups to the surface of SPIONs. The percentages of inorganic and organic content in the products were investigated via thermal gravimetric analyzer (TGA). For morphological analysis, a transmission electron microscope (TEM) was used. The superparamagnetic property of the product was also confirmed by vibrating sample magnetometer (VSM).     

Targeted anticancer prodrug with mesoporous silica nanoparticles as vehicles

A targeted anticancer prodrug system was fabricated with 180?nm mesoporous silica nanoparticles (MSNs) as carriers. The anticancer drug doxorubicin (DOX) was conjugated to the particles through an acid-sensitive carboxylic hydrazone linker which is cleavable under acidic conditions. Moreover, folic acid (FA) was covalently conjugated to the particle surface as the targeting ligand for folate receptors (FRs) overexpressed in some cancer cells. The in vitro release profiles of DOX from the MSN-based prodrug systems showed a strong dependence on the environmental pH values. The fluorescent dye FITC was incorporated in the MSNs so as to trace the cellular uptake on a fluorescence microscope. Cellular uptakes by HeLa, A549 and L929 cell lines were tested for FA-conjugated MSNs and plain MSNs respectively, and a much more efficient uptake by FR-positive cancer cells (HeLa) can be achieved by conjugation of folic acid onto the particles because of the folate-receptor-mediated endocytosis. The cytotoxicities for the FA-conjugated MSN prodrug, the plain MSN prodrug and free DOX against three cell lines were determined, and the result indicates that the FA-conjugated MSN prodrug exhibits higher cytotoxicity to FR-positive cells, and reduced cytotoxicity to FR-negative cells. Thus, with 180?nm MSNs as the carriers for the prodrug system, good drug loading, selective targeting and sustained release of drug molecules within targeted cancer cells can be realized. This study may provide useful insights for designing and improving the applicability of MSNs in targeted anticancer prodrug systems.     

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.     

Anticancer Activity of Self-Assembled Molecular Rectangles via Arene-Ruthenium Acceptors and a New Unsymmetrical Amide Ligand

Two new and large molecular rectangles 4 and 5 were synthesized from two different arene-ruthenium [Ru(2)(μ-η(4)-C(2)O(4))(MeOH)(2)(η(6)-p-Pr(i)C(6)H(4)Me)(2)][O(3)SCF(3)](2) (2), and [Ru(2) (p-cymene)(2) (donq) (OH(2))(2)] [O(3)SCF(3)](2) (donq = 5,8-dioxydo-1,4-naphthaquinonato) (3) acceptors and a new unsymmetrical N-(4-(pyridin-4-ylethynyl)phenyl) isonicotinamide (1) donor ligand. X-ray crystallography of 4 confirmed a molecular rectangle. The (1)H NMR spectra of both rectangles 4 and 5 showed a mixture of two structural, head-to-tail (HTL) and head-to-head (HTH) type, isomers in a 1:1 ratio. The cytotoxicities of both rectangles have been established against Colo320 (colorectal cancer), A549 (lung cancer), MCF-7(breast cancer) and H1299 (lung cancer) human cancer cell lines. The cytotoxicity of rectangle 5 was found to be considerably stronger against all cancer cell lines than that of the reference drug cisplatin.     

Eco-friendly green synthesis of silver nanoparticles and their potential applications as antioxidant and anticancer agents

Abstract

Eco-friendly green synthesis of nanoparticles using medicinal plants gained immense importance due to its potential therapeutic uses. In the current study, silver nanoparticles (AgNPs) were synthesized using water extract of Jurinea dolomiaea leaf and root at room temperature. MTT assay was used to study anticancer potential of AgNPs against cervical cancer cell line (HeLa), breast cancer cell lines (MCF-7), and mouse embryonic fibroblast (NIH-3 T3) cell line for toxicity evaluation. The antioxidant potential was evaluated using stable DPPH radicals. In addition, the apoptotic nuclear changes prompted by AgNPs in more susceptible HeLa cells were observed using fluorescence microscope through DAPI and PI staining. Physiochemical properties of biosynthesized AgNPs were characterized using various techniques. AgNPs were formed in very short time and UV–vis spectra showed characteristic absorption peak of AgNPs. SEM and TEM showed spherical shape of AgNPs and XRD revealed their crystalline nature. EDX analysis revealed high percentage of silver in green synthesized AgNPs. FTIR analysis indicated involvement of secondary metabolites in fabrication of AgNPs. In vitro cytotoxic and antioxidant study revealed that herb and biosynthesized AgNPs exhibited significant dose-dependent and time-dependent anticancer and antioxidant potential. Furthermore, study on normal cell line and microscopic analysis of apoptosis revealed that AgNPs exhibited good safety profile as compared to cisplatin and induces significant apoptosis effect. Based on the current findings, it is strongly believe that use of J. dolomiaea offers large scale production of biocompatible AgNPs that can be used as alternative anticancer agents against cancer cell lines tested.     

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 IC(50) 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.     

Green synthesis of biocompatible gold nanoparticles using Fagopyrum esculentum leaf extract

This report describes the use of ethnolic extract of Fagopyrum esculentum leaves for the synthesis of gold nanoparticles. UV-visible spectroscopy analysis indicated the successful formation of gold nanoparticles. The synthesized nanoparticles were characterized by transmission electron microscopy (TEM), high resolution TEM (HRTEM) and were found to be spherical, hexagonal and triangular in shape with an average size of 8.3 nm. The crystalline nature of the gold nanoparticles was confirmed from X-ray diffraction (XRD) and selected-area electron diffraction (SAED) patterns. Fourier transform infrared (FT-IR) and energy-dispersive X-ray analysis (EDX) suggested the presence of organic biomolecules on the surface of the gold nanoparticles. Cytotoxicity tests against human HeLa, MCF-7 and IMR-32 cancer cell lines revealed that the gold nanoparticles were non-toxic and thus have potential for use in various biomedical applications.     

Paclitaxel-loaded hollow-poly(4-vinylpyridine) nanoparticles enhance drug chemotherapeutic efficacy in lung and breast cancer cell lines

Paclitaxel (PTX),one of the most effective cytotoxins for the treatment of breast and lung cancer,is limited by its severe side effects and low tumor selectivity.In this work,hollow-poly(4-vinylpyridine) (hollow-p4VP) nanoparticles (NPs) have been used for the first time to generate PTX@p4VP NPs,employing a novel technique in which a gold core in the center of the NP is further oxidized to produce the hollow structure into which PTX molecules can be incorporated.The hollow-p4VP NPs exhibit good physicochemical properties and displayed excellent biocompatibility when tested on blood (no hemolysis) and cell cultures (no cytotoxicity).Interestingly,PTX@p4VP NPs significantly increased PTX cytotoxicity in human lung (A-549) and breast (MCF-7) cancer cells with a significant reduction of PTX IC50 (from 5.9 to 3.6 nM in A-549 and from 13.75 to 4.71 nM in MCF-7).In addition,PTX@p4VP caused a decrease in volume of A-549 and MCF-7 multicellular tumor spheroids (MTS),an in vitro system that mimics in vivo tumors,in comparison to free PTX.This increased antitumoral activity is accompanied by efficient cell internalization and increased apoptosis,especially in lung cancer MTS.Our results offer the first evidence that hollowp4VP NPs can improve the antitumoral activity of PTX.This system can be used as a new nanoplatform to overcome the limitations of current breast and lung cancer treatments.     

Acid-activatable doxorubicin prodrug micelles with folate-targeted and ultra-high drug loading features for efficient antitumor drug delivery

Stimuli-responsive nanomedicine shows high therapeutic effects and low side effects to tumor cells and tissues, representing a preferable therapeutics for cancer therapy. Herein, we design an acid-stimuli-responsive doxorubicin polymeric prodrug (OM@DOX), and this amphiphilic prodrug has a unique chemical structure with prominent advantages, including high drug loading rate (as high as 61.5 wt%), pH-triggered drug release and targeted access to cells. This smart polymeric prodrug has a preferable size of ~40 nm and strong micellar stability in aqueous solution, which is benefited to the long blood circulation and efficient extravasation from tumor vessel. Moreover, the prodrug micelles showed a higher cytotoxicity against tumor cells (HeLa cells) than normal cells (L929 cells), likely suggesting the potential tumor-specific targeting ability. To render this prodrug micelles with targeting function, folic acid (FA) molecules conjugated prodrug (FA-OM@DOX) further showed selectively higher cytotoxicity to KB tumor cells (FA-receptor-positive) than A549 tumor cells (FA-receptor-negative). Considering the rapidly cell-penetrating ability and aforementioned features, we believe that the present prodrug strategy has the potential as a promising nanomedicine and providing inspired insights to design multifunctional drug delivery nanoplatforms.     

Targeted delivery of melittin to cancer cells by AS1411 anti-nucleolin aptamer

Melittin, a small water-soluble cationic amphipathic α-helical linear peptide, consisted of 26 amino acids, is the honeybee venom major constituent. Several reports have proved the lytic and apoptotic effects of melittin in several cancerous cell lines. In this study, we aimed to fabricate an AS1411 aptamer–melittin to specifically deliver melittin to nucleolin positive cells (A549). Melittin was covalently attached to antinucleolin aptamer (AS1411) and its toxicity in A549 (nucleolin positive) and L929 (nucleolin negative) was studied using MTT and Annexin V flow cytometry methods. Aptamer–melittin conjugate formation was confirmed by gel electrophoresis. Hemolytic effect of aptamer–melittin conjugate was compared to melittin alone. The aptamer–melittin conjugate showed efficient cell uptake and was more cytotoxic in A549 cells than melittin (p?in vitro. This system can reduce the cytotoxic effects of melittin on cells with no nucleolin receptor overexpression which comprise most of normal cells such as L929 cells.     

Lobelia trigona Roxb ‐based nanomedicine with enhanced biological applications: in vitro and in vivo approach

This is the first study to report the green synthesis of Lobelia trigona Roxb‐ mediated silver nanoparticles (LTAgNPs). The optical and structural properties of the synthesised LTAgNPs were analysed using ultraviolet–visible spectroscopy, scanning electron microscopy, Fourier transform infrared, dynamic light scattering and energy dispersive X‐ray. LTAgNps were evaluated for their anti‐bacterial and anti‐fungal properties against 18 pathogens and exhibited significant inhibition against all the strains tested. LTAgNPs had potential scavenging effects on the DPPH, ^• OH, O₂ ^•− free radical scavenging assays and reducing power assay. LTAgNps possess strong anti‐cancer activity against five human cancer cell lines (A549, MCF‐7, MDA‐MB‐231, HeLa and KB) in a dose‐dependent manner. The antiproliferative, anti‐inflammatory and genotoxicity effects of LTAgNPs were further confirmed by the lactate dehydrogenase release assay, nitric oxide inhibitory assay and comet assay. Furthermore, the incision, excision and burn wound‐healing activity of formulated LTAgNPs ointment was assessed in rats. All the wounds had significant healing in groups treated with LTAgNPs ointment compared to the groups treated with the commonly prescribed ointment (Silverex^TM). This study shows and suggests that the previously unreported LTAgNPs could be used as a nanomedicine with significant biological applications.Inspec keywords: molecular biophysics, biomedical materials, scanning electron microscopy, biochemistry, cancer, microorganisms, silver, cellular biophysics, nanofabrication, wounds, nanomedicine, ultraviolet spectra, toxicology, antibacterial activity, light scattering, nanoparticles, enzymes, visible spectra, Fourier transform infrared spectraOther keywords: Lobelia trigona Roxb‐based nanomedicine, biological applications, Lobelia trigona Roxb‐mediated silver nanoparticles, optical properties, structural properties, ultraviolet‐visible spectroscopy, dynamic light scattering, antibacterial properties, antifungal properties, scavenging effects, free radical scavenging, power assay, anticancer activity, antiinflammatory effects, genotoxicity effects, lactate dehydrogenase release assay, nitric oxide inhibitory assay, excision, burn wound‐healing activity, formulated LTAgNPs ointment, in vivo approach, in vitro approach, scanning electron microscopy, Fourier transform infrared spectroscopy, energy dispersive X‐ray analysis, pathogens, strains, A549 human cancer cell lines, MCF‐7 human cancer cell lines, MDA‐MB‐231 human cancer cell lines, HeLa human cancer cell lines, antiproliferative effects, comet assay, Ag     

Evaluation of biotinylated magnetic nanoparticles for tumour imaging

Target-specific nanoparticles with good stability, dispersibility and targeting properties are very desirable for in vivo applications like diagnosis and therapy. In this work, the potential of covalently biotinylated magnetic nanoparticles for targeting tumours has been analysed by various in vitro and in vivo studies. For quantitatively estimating the amount of biotin bound to the surface of magnetic nanoparticles, 4-Hydroxyazobenzene-2-carboxylic acid dye was used. Varying the pH conditions changes, the mean size and zeta potential and transverse relaxivity slightly, affects the contrast enhancing capability of the synthesized biotinylated magnetic nanoparticles minimally. Cytotoxicity of the synthesized nanoconjugate was analysed in two different cell lines HeLa and A549 by using sulpho-rhodamine B assay and tumour cell-targeting capability was analysed in HeLa cell lines by using confocal microscopy. The results of cytotoxicity analysis combined with intracellular uptake, biodistribution and gamma scintigraphy prove the tumour-targeting potential of the synthesized biocompatible biotinylated magnetic nanoparticle conjugate.     

The pH-controlled nanoparticles size of polydopamine for anti-cancer drug delivery

A facile method was used to prepare polydopamine (PDA) nanoparticles. The effect of the initial pH of the dopamine solution on the formation kinetics, chemical structure, and biocompatibility of PDA nanoparticles was evaluated. Additionally, camptothecin (CPT) was chosen as a model anti-cancer drug with which to evaluate the efficiency of drug loading and release behavior of PDA nanoparticles. The results indicated that the size and yield of PDA nanoparticles, consisting of quinoid and indoline species, were closely related to the pH value of the precursor solution. At a reaction time of 6 h, the uniform particle sizes of PDA nanoparticles were ~400, 250, 150, and 75 nm in solutions with initial pH values of 7.5, 8, 8.5, and 9, respectively, and with corresponding yields of 3, 7, 20, and 34 %. The amounts of CPT loaded in 1 mg of PDA nanoparticles synthesized at pH values of 7.5, 8, 8.5, and 9 for 6 h were 10.85, 11.81, 10.17, and 6.19 μg, respectively. After the first day, 19, 20, 25, and 36 % of the CPT was released from PDA nanoparticles synthesized at pH values of 7.5, 8, 8.5, and 9, respectively, depending on the particle size. The PDA nanoparticles had excellent haemocompatibility: there was no apparent hemolysis, and they did not cause acute toxicity in A549 and HeLa cells. The loading of CPT into PDA nanoparticles significantly reduced the viability of A549 and HeLa cells, comparable to free CPT. It can be concluded that the PDA nanoparticles prepared by our facile method are potential carriers of anticancer drugs for cancer therapy.     

Epirubicin‐Loaded Superparamagnetic Iron‐Oxide Nanoparticles for Transdermal Delivery: Cancer Therapy by Circumventing the Skin Barrier

The transdermal administration of chemotherapeutic agents is a persistent challenge for tumor treatments. A model anticancer agent, epirubicin (EPI), is attached to functionalized superparamagnetic iron‐oxide nanoparticles (SPION). The covalent modification of the SPION results in EPI–SPION, a potential drug delivery vector that uses magnetism for the targeted transdermal chemotherapy of skin tumors. The spherical EPI–SPION composite exhibits excellent magnetic responsiveness with a saturation magnetization intensity of 77.8 emu g^?1. They feature specific pH‐sensitive drug release, targeting the acidic microenvironment typical in common tumor tissues or endosomes/lysosomes. Cellular uptake studies using human keratinocyte HaCaT cells and melanoma WM266 cells demonstrate that SPION have good biocompatibility. After conjugation with EPI, the nanoparticles can inhibit WM266 cell proliferation; its inhibitory effect on tumor proliferation is determined to be dose‐dependent. In vitro transdermal studies demonstrate that the EPI–SPION composites can penetrate deep inside the skin driven by an external magnetic field. The magnetic‐field‐assisted SPION transdermal vector can circumvent the stratum corneum via follicular pathways. The study indicates the potential of a SPION‐based vector for feasible transdermal therapy of skin cancer.     

Surface modified superparamagnetic iron oxide nanoparticles: as a new carrier for bio-magnetically targeted therapy

Amino-functionalized superparamagnetic iron oxide nanoparticles (SPION) were synthesized by coprecipitation method. The particles were characterized by X-ray diffraction (XRD), vibrating sample magnetometer (VSM), scanning electron micrographs (SEM), transmission electron micrographs (TEM) and atomic force micrographs (AFM). The size of the modified particles varied in the range 10–15 nm and did not change significantly after modification. Hepama-1, an excellent humanized monoclonal antibody directed against liver cancer, was conjugated to the SPION to prepare immuno-magnetic nanoparticles (IMN). A direct labeling method was employed to radiolabel IMN with rhenium-188. The radiolabeling efficiency was about 90% with good in vitro stability. ¹⁸⁸Re labeled IMN could markedly kill SMMC-7721 liver cancer cells. Such SPION might be very useful for bio-magnetically targeted radiotherapy in liver cancer treatment.     

Ruthenium- and Osmium-Arene Complexes of 2-Substituted Indolo[3,2-c]quinolines: Synthesis, Structure, Spectroscopic Properties, and Antiproliferative Activity

The synthesis of new modified indolo[3,2-c]quinoline ligands L(1)-L(8) with metal-binding sites is reported. By coordination to ruthenium- and osmium-arene moieties 16 complexes of the type [(η(6)-p-cymene)M(L)Cl]Cl (1a,b-8a,b), where M is Ru(II) or Os(II) and L is L(1)-L(8), have been prepared. All compounds were comprehensively characterized by elemental analysis, electrospray ionization mass spectrometry, IR, UV-vis, and NMR spectroscopy, thermogravimetric analysis, and single-crystal X-ray diffraction (2a, 4a, 4b, 5a, 7a, and 7b). The complexes were tested for antiproliferative activity in vitro in three human cancer cell lines, namely, CH1 (ovarian carcinoma), SW480 (colon adenocarcinoma), and A549 (non-small-cell lung cancer), yielding IC(50) values in the submicromolar or low micromolar range.     

Enhancement of radiation cytotoxicity in breast-cancer cells by localized attachment of gold nanoparticles

Gold nanoparticles (GNPs) and modified GNPs having two kinds of functional molecules, cysteamine (AET) and thioglucose (Glu), are synthesized. Cell uptake and radiation cytotoxicity enhancement in a breast-cancer cell line (MCF-7) versus a nonmalignant breast-cell line (MCF-10A) are studied. Transmission electron microscopy (TEM) results show that cancer cells take up functional Glu-GNPs significantly more than naked GNPs. The TEM results also indicate that AET-capped GNPs are mostly bound to the MCF-7 cell membrane, while Glu-GNPs enter the cells and are distributed in the cytoplasm. After MCF-7 cell uptake of Glu-GNPs, or binding of AET-GNPs, the in vitro cytotoxicity effects are observed at 24, 48, and 72 hours. The results show that these functional GNPs have little or no toxicity to these cells. To validate the enhanced killing effect on cancer cells, various forms of radiation are applied such as 200 kVp X-rays and gamma-rays, to the cells, both with and without functional GNPs. By comparison with irradiation alone, the results show that GNPs significantly enhance cancer killing.     

Efficacy of green nanoparticles against cancerous and normal cell lines: a systematic review and meta‐analysis

This study aimed to perform a systematic review and meta‐analysis of papers discussing the efficacy of microbial synthesised metallic nanoparticles (MNPs) against cancerous and normal cell lines by exploiting Bayesian generalised linear (BGL) model. Data was systematically collected from published papers via Cochrane library, Web of Science, PubMed, Science Direct, ProQuest, Scopus, and Embase. Impressively, most of the studies were carried out on HeLa and A549 cancer cell lines. Specifically, a hefty 65.67% of studies employed bacteria to biofabricate MNPs. Significantly, BGL meta‐analysis represented highly valuable information. Hence, based on adjusted analysis, the MNPs with the size of 25–50 nm were found to be far less cytotoxic than the MNPs with the size of ≤25 nm (OR = 0.233, P  ˂ 0.05) against either cancerous or normal cell lines. Interestingly, it was found that the odds of cytotoxicity in cancerous cell lines were practically nine times more than normal cell lines, representing the substantially more cytotoxicity of MNPs in cancerous cell lines (OR = 9.004, P  ˂ 0.001). Green MNPs mentioned here may be developed as novel anti‐cancer agents, which could lead to a revolution in the treatment of cancer.Inspec keywords: reviews, nanoparticles, cancer, nanomedicine, magnetic particles, nanomagnetics, nanofabrication, cellular biophysics, Bayes methods, microorganisms, toxicology, antibacterial activityOther keywords: green nanoparticles, cancerous cell lines, normal cell lines, review, meta‐analysis, microbial synthesised metallic nanoparticles, Bayesian generalised linear model, HeLa cancer cell lines, A549 cancer cell lines, gram‐negative bacteria, gram‐positive bacteria, cytotoxicity, anticancer agents, cancer disease treatment     

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.     

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.