Modeling Absorption Dynamics of Differently Shaped Gold Glioblastoma and Colon Cells Based on Refractive Index Distribution in Holotomographic Imaging.

Herein, it is demonstrated that the toxic effect of gold nanoparticles (Au NPs) on three different cancer cell lines (U-118 and LN-299 glioblastoma and HCT-116 colon) depends on their absorption dynamics by cells, related to the shapes of the NPs. This hypothesis is confirmed by showing that i) based on refractive index (RI) values, typical for cell components and gold nanoparticles, it is possible to show the absorption dynamics and accumulation locations of the latter ones inside and outside of the cells. Moreover, ii) the saturation of the accumulated Au NPs volume in the cells depends on the nanoparticle shape and is reached in the shortest time for star-shaped Au NPs (AuS NPs) and in the longest time for spherical Au NPs (AuSph NPs) and on the cancer cells, where the longest and the shortest saturation are noticed for HCT-116 and LN-229 cells, respectively. A physical model of Au NPs absorption dynamics is proposed, where the diameter and shape of the Au NPs are used as parameters. The obtained theoretical data are consistent with experimental data in 85-98%.

Improving the Effect of Cancer Cells Irradiation with X-rays and High-Energy Protons Using Bimetallic Palladium-Platinum Nanoparticles with Various Nanostructures.

Nano-sized radiosensitizers can be used to increase the effectiveness of radiation-based anticancer therapies. In this study, bimetallic, ~30 nm palladium-platinum nanoparticles (PdPt NPs) with different nanostructures (random nano-alloy NPs and ordered core-shell NPs) were prepared. Scanning transmission electron microscopy (STEM), selected area electron diffraction (SAED), energy-dispersive X-ray spectroscopy (EDS), zeta potential measurements, and nanoparticle tracking analysis (NTA) were used to provide the physicochemical characteristics of PdPt NPs. Then, PdPt NPs were added to the cultures of colon cancer cells and normal colon epithelium cells in individually established non-toxic concentrations and irradiated with the non-harmful dose of X-rays/protons. Cell viability before and after PdPt NPs-(non) assisted X-ray/proton irradiation was evaluated by MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay. Flow cytometry was used to assess cell apoptosis. The results showed that PdPt NPs significantly enhanced the effect of irradiation on cancer cells. It was noticed that nano-alloy PdPt NPs possess better radiosensitizing properties compared to PtPd core-shell NPs, and the combined effect against cancer cells was c.a. 10% stronger for X-ray than for proton irradiation. Thus, the radio-enhancing features of differently structured PdPt NPs indicate their potential application for the improvement of the effectiveness of radiation-based anticancer therapies.

Correlation between endometriomas volume and Raman spectra. Attempting to use Raman spectroscopy in the diagnosis of endometrioma.

The formation of the uterus lining, i.e. the endometrium, outside the uterus (ex. in the abdominal cavity,ovaries,or anywhere in the body) is called endometriosis. The presence of endometrial tissue present in the ovaries, thickens after menstruation, leading to menstrual-like bleeding and to the formation of chocolate cyst (Endometrioma) because of the accumulation of old, brown blood in the ovary. It is still unknown, what triggers the development ofendometrioma. However,it leads to excessive bleeding during menstrual periods or abnormal bleeding between periods and infertility. Endometriosis is often first diagnosed in those who seek medical attention for infertility. Therefore, new markers of endometrioma as well as new methods of its diagnosis are sought. In this study we used Raman spectra of serum collected from 50 healthy women and 50 women suffering from endometriosis. The obtained Raman data were used in multivariateanalysis to determine the Raman range, which can be used for endometriomadiagnostics. Partial Least Square (PLS), Principal Component Analysis (PCA) and Hierarchical Component Analysis (HCA) showed, that it is possible to distinguish between the serum collected from healthy and un-healthy women using the Raman range between 800 cm-1 and 1800 cm-1 and between 2956 cm-1 and 2840 cm-1, while the first range corresponds to the fingerprint region and the second one to lipids vibrations. Consequently, the Pearson correlation test showeda significantpositive correlation betweenvaluesoflipidintensity in Raman spectra and volume of endometriomas. Summarizing, Raman spectroscopy can be a helpful tool in endometrioma diagnosis and the lipid vibrations are candidates for being a spectroscopic marker of the disease being studied.

N-Acetyl-Cysteine Increases Activity of Peanut-Shaped Gold Nanoparticles Against Biofilms Formed by Clinical Strains of Pseudomonas aeruginosa Isolated from Sputum of Cystic Fibrosis Patients.

Background: Extracellular polymeric substances (EPS) produced by bacteria, as they form a biofilm, determine the stability and viscoelastic properties of biofilms and prevent antibiotics from penetrating this multicellular structure. To date, studies demonstrated that an appropriate optimization of the chemistry and morphology of nanotherapeutics might provide a favorable approach to control their interaction with EPS and/or diffusion within the biofilm matrix. Targeting the biofilms' EPS, which in certain conditions can adopt liquid crystal structure, was demonstrated to improve the anti-biofilm activity of antibiotics and nanoparticles. A similar effect is achievable by interfering EPS' production by mucoactive agents, such as N-acetyl-cysteine (NAC). In our previous study, we demonstrated the nanogram efficiency of non-spherical gold nanoparticles, which due to their physicochemical features, particularly morphology, were noted to be superior in antimicrobial activity compared to their spherical-shaped counterparts. Methods: To explore the importance of EPS matrix modulation in achieving a suitable efficiency of peanut-shaped gold nanoparticles (AuP NPs) against biofilms produced by Pseudomonas aeruginosa strains isolated from cystic fibrosis patients, fluorescence microscopy, as well as resazurin staining were employed. Rheological parameters of AuP NPs-treated biofilms were investigated by rotational and creep-recovery tests using a rheometer in a plate-plate arrangement. Results: We demonstrated that tested nanoparticles significantly inhibit the growth of mono- and mixed-species biofilms, particularly when combined with NAC. Notably, gold nanopeanuts were shown to decrease the viscosity and increase the creep compliance of Pseudomonas biofilm, similarly to EPS-targeting NAC. Synergistic activity of AuP NPs with tobramycin was also observed, and the AuP NPs were able to eradicate bacteria within biofilms formed by tobramycin-resistant isolates. Conclusion: We propose that peanut-shaped gold nanoparticles should be considered as a potent therapeutic agent against Pseudomonas biofilms.

Identification of polycystic ovary syndrome from blood serum using hormone levels via Raman spectroscopy and multivariate analysis.

Polycystic ovarian syndrome (PCOS) is a disease, which causes infertility in women. The factors for the development of the disease are still not well understood and diagnostic methods need to be improved. Therefore, in this study, Raman spectroscopy as a potential diagnostic tool, was investigated and spectra of blood serum were collected from PCOS and healthy women. The obtained spectra showed distinct changes in intensities as well as shift of peaks for the blood serum collected from PCOS compared to healthy individuals. Partial Last Square (PLS) analysis and Principal Component Analysis (PCA) allowed to determine that Raman shifts of amides (1500 - 1700 cm-1) and CH2, CH3 lipid groups (2700 - 3000 cm-1), could be thus used as potential PCOS markers. Furthermore, the Pearson correlation test showed a strong correlation between hormones (lutropin (LH), prolactin (PRL), follicle-stimulating (FSH), dehydroepiandrosterone (DHEAS), thyroid-stimulating (TSH), Estradiol) and lipids, as well as between hormones and protein functional groups in PCOS women, compared to the control. These results show, that the lipid and protein balance could be potentially applied as a helpful PCOS marker in Raman spectra.

Differential of cholangiocarcinoma disease using Raman spectroscopy combined with multivariate analysis.

Cholangiocarcinoma (CCA) is a type of cancer, which 5-year survival is lower than 20 %, and which is detected mostly in advanced stage of the disease. Unfortunately, there are no diagnostic tools, which could show changes in the body indicating the development of the disease. Therefore, in this study, we investigate Raman spectroscopy as a promising analytical tool in medical diagnostics and as a method, which would allow to distinguish between healthy patients and patients suffering from cholangiocarcinoma. The obtained Raman spectra showed, that lower intensities of peaks corresponding to amino acids and proteins, as well as higher intensities of peaks originating from lipids vibrations were observed in healthy individuals in comparison with cancer patients. Moreover, Partial Last Square (PLS), Principal Component Analysis (PCA) and Hierarchical Component Analysis (HCA) of Raman spectra indicate that the ranges between 800 cm-1 and 1800 cm-1, 3477 cm-1 -3322 cm-1 and 1394 cm-1 -1297 cm-1 allow to distinguish cancer patients from healthy ones. The obtained results showed, that Raman spectroscopy is a good candidate, to become in future one of the diagnostic tools of Cholangiocarcinoma.

Ceragenin-Coated Non-Spherical Gold Nanoparticles as Novel Candidacidal Agents.

BACKGROUND: Infections caused by Candida spp. have become one of the major causes of morbidity and mortality in immunocompromised patients. Therefore, new effective fungicides are urgently needed, especially due to an escalating resistance crisis. METHODS: A set of nanosystems with rod- (AuR), peanut- (AuP), and star-shaped (AuS) metal cores were synthesized. These gold nanoparticles were conjugated with ceragenins CSA-13, CSA-44, and CSA-131, and their activity was evaluated against Candida strains (n = 21) through the assessment of MICs (minimum inhibitory concentrations)/MFCs (minimum fungicidal concentrations). Moreover, in order to determine the potential for resistance development, serial passages of Candida cells with tested nanosystems were performed. The principal mechanism of action of Au NPs was evaluated via ROS (reactive oxygen species) generation assessment, plasma membrane permeabilization, and release of the protein content. Finally, to evaluate the potential toxicity of Au NPs, the measurement of hemoglobin release from red blood cells (RBCs) was carried out. RESULTS: All of the tested nanosystems exerted a potent candidacidal activity, regardless of the species or susceptibility to other antifungal agents. Significantly, no resistance development after 25 passages of Candida cells with AuR@CSA-13, AuR@CSA-44, and AuR@CSA-131 nanosystems was observed. Moreover, the fungicidal mechanism of action of the investigated nanosystems involved the generation of ROS, damage of the fungal cell membrane, and leakage of intracellular contents. Notably, no significant RBCs hemolysis at candidacidal doses of tested nanosystems was detected. CONCLUSIONS: The results provide rationale for the development of gold nanoparticles of rod-, peanut-, and star-shaped conjugated with CSA-13, CSA-44, and CSA-131 as effective candidacidal agents.

Targeting bacteria causing otitis media using nanosystems containing nonspherical gold nanoparticles and ceragenins.

Aim: To evaluate the antibacterial and antibiofilm activity of ceragenin-conjugated nonspherical gold nanoparticles against the most common agents of otitis media. Methods: Minimal inhibitory and bactericidal concentrations and colony-counting assays, as well as colorimetric and fluorimetric methods, were used to estimate the antibacterial activity of compounds in phosphate-buffered saline and human cerumen. The nanosystems' biocompatibility and ability to decrease IL-8 release was tested using keratinocyte cells. Results: The tested compounds demonstrated strong antimicrobial activity against planktonic and biofilm cultures at nontoxic doses due to the induction of oxidative stress followed by the damage of bacterial membranes. Conclusion: This study indicates that ceragenin-conjugated nonspherical gold nanoparticles have potential as new treatment methods for eradicating biofilm-forming pathogens associated with otitis media.

Lay abstract Middle-ear infections can be painful and cause hearing difficulties. If untreated, they can lead to hearing loss. These infections are usually treated with antibiotic drugs. However, the microbes causing the infection can gain drug resistance. This article reports research into a new way of delivering antibiotics to kill the microbes and the communities they form (biofilms). The authors developed tiny gold particles loaded with the antimicrobial drug ceragenin and tested the drug-loaded particles on three common middle-ear infection-causing bacteria. Compared with ceragenin alone, the ceragenin-loaded particles were better at killing the bacteria and their biofilm communities.

Peanut-Shaped Gold Nanoparticles with Shells of Ceragenin CSA-131 Display the Ability to Inhibit Ovarian Cancer Growth In Vitro and in a Tumor Xenograft Model.

Gold nanoparticles-assisted delivery of antineoplastics into cancerous cells is presented as an effective approach for overcoming the limitations of systemic chemotherapy. Although ceragenins show great potential as anti-cancer agents, in some tumors, effective inhibition of cancer cells proliferation requires application of ceragenins at doses within their hemolytic range. For the purpose of toxicity/efficiency ratio control, peanut-shaped gold nanoparticles (AuP NPs) were functionalized with a shell of ceragenin CSA-131 and the cytotoxicity of AuP@CSA-131 against ovarian cancer SKOV-3 cells and were then analyzed. In vivo efficiency of intravenously and intratumorally administered CSA-131 and AuP@CSA-131 was examined using a xenograft ovarian cancer model. Serum parameters were estimated using ELISA methods. Comparative analysis revealed that AuP@CSA-131 exerted stronger anti-cancer effects than free ceragenin, which was determined by enhanced ability to induce caspase-dependent apoptosis and autophagy processes via reactive oxygen species (ROS)-mediated pathways. In an animal study, AuP@CSA-131 was characterized by delayed clearance and prolonged blood circulation when compared with free ceragenin, as well as enhanced anti-tumor efficiency, particularly when applied intratumorally. Administration of CSA-131 and AuP@CSA-131 prevented the inflammatory response associated with cancer development. These results present the possibility of employing non-spherical gold nanoparticles as an effective nanoplatform for the delivery of antineoplastics for the treatment of ovarian malignancy.

Gold-Decorated Platinum and Palladium Nanoparticles as Modern Nanocomplexes to Improve the Effectiveness of Simulated Anticancer Proton Therapy.

Noble metal nanoparticles, such as gold (Au NPs), platinum (Pt NPs), or palladium (Pd NPs), due to their highly developed surface, stability, and radiosensitizing properties, can be applied to support proton therapy (PT) of cancer. In this paper, we investigated the potential of bimetallic, c.a. 30 nm PtAu and PdAu nanocomplexes, synthesized by the green chemistry method and not used previously as radiosensitizers, to enhance the effect of colorectal cancer PT in vitro. The obtained nanomaterials were characterized by scanning transmission electron microscopy (STEM), selected area electron diffraction (SAED), energy-dispersive X-ray spectroscopy (EDS), UV-Vis spectroscopy, and zeta potential measurements. The effect of PtAu and PdAu NPs in PT was investigated on colon cancer cell lines (SW480, SW620, and HCT116), as well as normal colon epithelium cell line (FHC). These cells were cultured with both types of NPs and then irradiated by proton beam with a total dose of 15 Gy. The results of the MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) test showed that the NPs-assisted PT resulted in a better anticancer effect than PT used alone; however, there was no significant difference in the radiosensitizing properties between tested nanocomplexes. The MTS results were further verified by defining the cell death as apoptosis (Annexin V binding assay). Furthermore, the data showed that such a treatment was more selective for cancer cells, as normal cell viability was only slightly affected.

Varied-shaped gold nanoparticles with nanogram killing efficiency as potential antimicrobial surface coatings for the medical devices.

Medical device-associated infections are a serious medical threat, particularly for patients with impaired mobility and/or advanced age. Despite a variety of antimicrobial coatings for medical devices being explored to date, only a limited number have been introduced for clinical use. Research into new bactericidal agents with the ability to eradicate pathogens, limit biofilm formation, and exhibit satisfactory biocompatibility, is therefore necessary and urgent. In this study, a series of varied-morphology gold nanoparticles in shapes of rods, peanuts, stars and spherical-like, porous ones with potent antibacterial activity were synthesized and thoroughly tested against spectrum of Candida albicans, Pseudomonas aeruginosa, Staphylococcus aureus clinical strains, as well as spectrum of uropathogenic Escherichia coli isolates. The optimization of gold nanoparticles synthesis allowed to develop nanomaterials, which are proved to be significantly more potent against tested microbes compared with the gold nanoformulations reported to date. Notably, their antimicrobial spectrum includes strains with different drug resistance mechanisms. Facile and cost-efficient synthesis of gold nanoparticles, remarkable bactericidal efficiency at nanogram doses, and low toxicity, underline their potential for development as a new coatings, as indicated by the example of urological catheters. The presented research fills a gap in microbial studies of non-spherical gold nanoparticles for the development of antimicrobial coatings targeting multidrug-resistant pathogens responsible for device-associated nosocomial infections.

Bactericidal Properties of Rod-, Peanut-, and Star-Shaped Gold Nanoparticles Coated with Ceragenin CSA-131 against Multidrug-Resistant Bacterial Strains.

BACKGROUND: The ever-growing number of infections caused by multidrug-resistant (MDR) bacterial strains requires an increased effort to develop new antibiotics. Herein, we demonstrate that a new class of gold nanoparticles (Au NPs), defined by shape and conjugated with ceragenin CSA-131 (cationic steroid antimicrobial), display strong bactericidal activity against intractable superbugs. METHODS: For the purpose of research, we developed nanosystems with rod- (AuR NPs@CSA-131), peanut-(AuP NPs@CSA-131) and star-shaped (AuS NPs@CSA-131) metal cores. Those nanosystems were evaluated against bacterial strains representing various groups of MDR (multidrug-resistant) Gram-positive (MRSA, MRSE, and MLSb) and Gram-negative (ESBL, AmpC, and CR) pathogens. Assessment of MICs (minimum inhibitory concentrations)/MBCs (minimum bactericidal concentrations) and killing assays were performed as a measure of their antibacterial activity. In addition to a comprehensive analysis of bacterial responses involving the generation of ROS (reactive oxygen species), plasma membrane permeabilization and depolarization, as well as the release of protein content, were performed to investigate the molecular mechanisms of action of the nanosystems. Finally, their hemocompatibility was assessed by a hemolysis assay. RESULTS: All of the tested nanosystems exerted potent bactericidal activity in a manner resulting in the generation of ROS, followed by damage of the bacterial membranes and the leakage of intracellular content. Notably, the killing action occurred with all of the bacterial strains evaluated, including those known to be drug resistant, and at concentrations that did not impact the growth of host cells. CONCLUSIONS: Conjugation of CSA-131 with Au NPs by covalent bond between the COOH group from MHDA and NH3 from CSA-131 potentiates the antimicrobial activity of this ceragenin if compared to its action alone. Results validate the development of AuR NPs@CSA-131, AuP NPs@CSA-131, and AuS NPs@CSA-131 as potential novel nanoantibiotics that might effectively eradicate MDR bacteria.

ROS-Mediated Apoptosis and Autophagy in Ovarian Cancer Cells Treated with Peanut-Shaped Gold Nanoparticles.

BACKGROUND: Even with considerable improvement in treatment of epithelial ovarian cancer achieved in recent years, an increasing chemotherapy resistance and disease 5-year relapse is recorded for a majority part of patients that encourages the search for better therapeutic options. Gold nanoparticles (Au NPs) due to plethora of unique physiochemical features are thoroughly tested as drug delivery, radiosensitizers, as well as photothermal and photodynamic therapy agents. Importantly, due to highly controlled synthesis, it is possible to obtain nanomaterials with directed size and shape. METHODS: In this work, we developed novel elongated-type gold nanoparticles in the shape of nanopeanuts (AuP NPs) and investigated their cytotoxic potential against ovarian cancer cells SKOV-3 using colorimetric and fluorimetric methods, Western blot, flow cytometry, and fluorescence microscopy. RESULTS: Peanut-shaped gold nanoparticles showed high anti-cancer activity in vitro against SKOV-3 cells at doses of 1-5 ng/mL upon 72 hours treatment. We demonstrate that AuP NPs decrease the viability and proliferation capability of ovarian cancer cells by triggering cell apoptosis and autophagy, as evidenced by flow cytometry and Western blot analyses. The overproduction of reactive oxygen species (ROS) was noted to be a critical mediator of AuP NPs-mediated cell death. CONCLUSION: These data indicate that gold nanopeanuts might be developed as nanotherapeutics against ovarian cancer.

Fancy-Shaped Gold-Platinum Nanocauliflowers for Improved Proton Irradiation Effect on Colon Cancer Cells.

Enhancing the effectiveness of colorectal cancer treatment is highly desirable. Radiation-based anticancer therapy-such as proton therapy (PT)-can be used to shrink tumors before subsequent surgical intervention; therefore, improving the effectiveness of this treatment is crucial. The addition of noble metal nanoparticles (NPs), acting as radiosensitizers, increases the PT therapeutic effect. Thus, in this paper, the effect of novel, gold-platinum nanocauliflowers (AuPt NCs) on PT efficiency is determined. For this purpose, crystalline, 66-nm fancy shaped, bimetallic AuPt NCs were synthesized using green chemistry method. Then, physicochemical characterization of the obtained AuPt NCs by transmission electron microscopy (TEM), selected area electron diffraction (SAED), energy dispersive X-ray spectroscopy (EDS), and UV-Vis spectra measurements was carried out. Fully characterized AuPt NCs were placed into a cell culture of colon cancer cell lines (HCT116, SW480, and SW620) and a normal colon cell line (FHC) and subsequently subjected to proton irradiation with a total dose of 15 Gy. The 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) test, performed after 18-h incubation of the irradiated cell culture with AuPt NCs, showed a significant reduction in cancer cell viability compared to normal cells. Thus, the radio-enhancing features of AuPt NCs indicate their potential application for the improvement in effectiveness of anticancer proton therapy.

Gold Nanopeanuts as Prospective Support for Cisplatin in Glioblastoma Nano-Chemo-Radiotherapy.

Herein, we propose newly designed and synthesized gold nanopeanuts (Au NPes) as supports for cisplatin (cPt) immobilization, dedicated to combined glioblastoma nano-chemo-radiotherapy. Au NPes offer a large active surface, which can be used for drugs immobilization. Transmission electron microscopy (TEM) revealed that the size of the synthesized Au NPes along the longitudinal axis is ~60 nm, while along the transverse axis ~20 nm. Raman, thermogravimetric analysis (TGA) and differential scanning calorimetry (DCS) measurements showed, that the created nanosystem is stable up to a temperature of 110 °C. MTT assay revealed, that the highest cell mortality was observed for cell lines subjected to nano-chemo-radiotherapy (20-55%). Hence, Au NPes with immobilized cPt (cPt@AuNPes) are a promising nanosystem to improve the therapeutic efficiency of combined nano-chemo-radiotherapy.

Rod-shaped gold nanoparticles exert potent candidacidal activity and decrease the adhesion of fungal cells.

Aim: To investigate the fungicidal activity of rod-shaped gold nanoparticles (AuR NPs) against Candida strains isolated from hematooncological patients and representative strains of filamentous fungi. Methods: Colony-counting assays, colorimetric and fluorometric methods and atomic force microscopy were employed. Results: AuR NPs were characterized by their potent fungicidal activity against all tested isolates, regardless of the species or drug susceptibility, at concentrations that are nontoxic to the host cells. The membrane-permeabilizing properties of AuR NPs and induction of reactive oxygen species were recognized as crucial for fungicidal activity. Conclusions: The results provide a rationale for the development of nonspherical Au NPs as effective antifungals or drug-delivery carriers to improve therapy for fungal infections.

Raising the COx Methanation Activity of a Ru/γ-Al2 O3 Catalyst by Activated Modification of Metal-Support Interactions.

Ru/Al2 O3 is a highly stable, but less active catalyst for methanation reactions. Herein we report an effective approach to significantly improve its performance in the methanation of CO2 /H2 mixtures. Highly active and stable Ru/γ-Al2 O3 catalysts were prepared by high-temperature treatment in the reductive reaction gas. Operando/in situ spectroscopy and STEM imaging reveals that the strongly improved activity, by factors of 5 and 14 for CO and CO2 methanation, is accompanied by a flattening of the Ru nanoparticles and the formation of highly basic hydroxylated alumina sites. We propose a modification of the metal-support interactions (MSIs) as the origin of the increased activity, caused by modification of the Al2 O3 surface in the reductive atmosphere and an increased thermal mobility of the Ru nanoparticles, allowing their transfer to modified surface sites.

Similarities in the General Chemical Composition of Colon Cancer Cells and Their Microvesicles Investigated by Spectroscopic Methods-Potential Clinical Relevance.

Colon cancer constitutes 33% of all cancer cases in humans and the majority of patients with metastatic colon cancer still have poor prognosis. An important role in cancer development is the communication between cancer and normal cells. This may occur, among others, through extracellular vesicles (including microvesicles) (MVs), which are being released by both types of cells. MVs may regulate a diverse range of biological processes and are considered as useful cancer biomarkers. Herein, we show that similarity in the general chemical composition between colon cancer cells and their corresponding tumor-derived microvesicles (TMVs) does exist. These results have been confirmed by spectroscopic methods for four colon cancer cell lines: HCT116, LoVo, SW480, and SW620 differing in their aggressiveness/metastatic potential. Our results show that Raman and Fourier Transform InfraRed (FTIR) analysis of the cell lines and their corresponding TMVs did not differ significantly in the characterization of their chemical composition. However, hierarchical cluster analysis of the data obtained by both of the methods revealed that only Raman spectroscopy provides results that are in line with the molecular classification of colon cancer, thus having potential clinical relevance.

Fe3O4@SiO2@Au nanoparticles for MRI-guided chemo/NIR photothermal therapy of cancer cells.

Novel functionalized (biofunctionalization followed by cisplatin immobilization) Fe3O4@SiO2@Au nanoparticles (NPs) were designed. The encapsulation of Fe3O4 cores inside continuous SiO2 shells preserves their initial structure and strong magnetic properties, while the shell surface can be decorated by small Au NPs, and then cisplatin (cPt) can be successfully immobilized on their surface. The fabricated NPs exhibit very strong T 2 contrasting properties for magnetic resonance imaging (MRI). The functionalized Fe3O4@SiO2@Au NPs are tested for a potential application in photothermal cancer therapy, which is simulated by irradiation of two colon cancer cell lines (SW480 and SW620) with a laser (λ = 808 nm, W = 100 mW cm-2). It is found that the functionalized NPs possess low toxicity towards cancer cells (∼10-15%), which however could be drastically increased by laser irradiation, leading to a mortality of the cells of ∼43-50%. This increase of the cytotoxic properties of the Fe3O4@SiO2@Au NPs, due to the synergic effect between the presence of cPt plus Au NPs and laser irradiation, makes these NPs perspective agents for potential (MRI)-guided stimulated chemo-photothermal treatment of cancer.

Autologous tumor­derived microvesicles influence gene expression profiles and enhance protumorigenic chemotactic potential, signal transduction and cellular respiration in gastric cancer cells.

Tumor­derived microvesicles (TMVs) interact with a variety of different cell types within the immune system, including lymphocytes, monocytes, dendritic cells and tumor cells that they have originated from. In the present study, the effects of autologous­TMVs (auto­TMVs) on gene expression, chemotaxis, intercellular signaling and cellular metabolism were examined in cells of the gastric cancer (GC) cell line 1415 (GC1415). The effects of auto­TMVs on mRNA gene expression in GC1415 cells were assessed using pathway­focused PCR arrays. A chemotaxis assay was performed using the HoloMonitor M4 System. Signaling pathways were evaluated using western blot analysis, and cellular respiration was measured using the Seahorse XF Cell Mito Stress Test. Exposure of the GC1415 cells to auto­TMVs led to the overexpression (75 genes) and underexpression (96 genes) of genes that are associated with signal transduction, metabolism, chemotaxis, angiogenesis and metastasis. The auto­TMVs were indicated to induce chemotaxis and activate the PI3K/AKT signaling pathway in GC1415 cells. However, the MAPK/ERK signaling pathway was not indicated to be activated. Furthermore, studies on cellular respiration in GC1415 cells exposed to auto­TMVs demonstrated a metabolic shift to glycolysis. The results of the current study thus indicate that auto­TMVs may exert an effect on tumor cell function.