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Chemotherapy is one of the most effective approaches used to treat cancer, a leading cause of death worldwide.[1] Ruthenium-based complexes have emerged as a powerful alternative to state-of-the-art platinum chemotherapeutics due to their reduced toxicity, higher selectivity and anti-metastatic potential.[2] Here, we employ mass spectrometry and spectroscopic techniques to characterize a novel cis-[Ru(II)(dcbpy)2Cl2] complex and investigate its interaction with cellular lipids. In addition, the cytotoxic effect and mode of action on four standard cancer cell lines, namely melanoma A375, cervical cancer HeLa and pancreas ductal adenocarcinoma MIA PaCa-2 and PANC-1, were elucidated. Our results show a dose-dependent cytotoxicity of the complex on A375, MIA PaCa-2 and PANC-1. Further, the Ru(II) complex reduces the clonogenic potential caused by G1 arrest and increases ROS production in all tested cell lines. Lipid peroxidation is also observed in HeLa and MIA PaCa-2 cells, possibly indicating ferroptosis induction. Synchrotron radiation Fourier Transform Infrared Spectroscopy was applied to study the overall interaction of a Ru-complex with cellular biomolecules, and our results demonstrated a shift in bands in the lipid fingerprint area of most cell lines, confirming the lipid rearrangement process induced by the interaction with Ru(II) complex. The complex significantly increases the percentage of apoptotic A375, HeLa and MIA PaCa-2, while a significant decrease of p62 protein, a marker for autophagy induction, is detected solely in A375 cells. The wound healing assay revealed that the Ru(II) complex reduces the metastatic potential of HeLa and MIA PaCa-2 cells by reducing their migration ability. Overall, our results indicate the existence of a general mode of action of the tested Ru(II) complex that involves growth arrest and ROS production, as well as cancer cell line-specific effects. These involve dual role trough inducing programmed cell death - apoptosis and

Small, carbon-based nanoparticles, carbon dots (CDs), are investigated as photosensitizers (PSs) for photodynamic therapy of cancers. The results presented here show biochemical changes in cancer cells treated with surface-modified CDs, which are augmented by illumination, indicating a high potential of CDs as selective drug carriers and potent PSs. In addition, we will show that CDs produced from black carrot extract (biomass) can be exploited for image-guided therapy and be cytotoxic for cancer cells, thanks to their fluorescence properties. Finally, since biomass-fabricated CDs interact strongly with nucleic acids, they can be further developed for cell cycle sensing purposes.

With difficulty in early diagnosis, inaccessibility for the surgical approach, and high resistance to radio and chemotherapies, the resulting low treatment success rates are calling for new approaches in treating pancreatic cancer [1]. Photodynamic therapy (PDT), with the use of light or X-rays, is a method that has the potential to help overcome the problems that existing approaches meet [2,3]. Through activation of photo-sensitive particles with irradiation, PDT helps the production of reactive oxygen species, consequently stimulating cell death. We have synthesized and characterized Gadolinium-doped titanium dioxide nanoparticles (Gd-TiO2 NPs) and tested them as photosensitizers on two pancreatic cancer cell lines, MIA PaCa-2 and PANC-1. Different concentrations of NP treatment, irradiation powers, and times of irradiation were trialed as parameters of activation. Cell viability was measured 48h after treatments, and although some results implied a slight decrease in the viability of treated cells, we have met difficulties in obtaining consistency in results. Statistical significance in the decrease of the viability of treated cells in most cases was not attained, suggesting that higher concentrations or irradiation power and longer illumination time might be needed to achieve a positive PDT effect with this NP system.

In recent years researchers have developed new strategies to enhance the effectiveness of wound healing by combining nanoparticles and infra red (IR) light. For example, some studies have shown that nanoparticles can be used to enhance the absorption of near-infrared laser (NIR) light by tissues, leading to increased healing rates [1]. The influence of NIR light on proliferation, collagen production, and wound healing was tested on: keratocytes (HaCaT) and fibroblasts (MRC-5) cells that are used as model systems of human skin equivalents that comprise an epidermal and a dermal compartment of skin. Also, these cells were treated with carbon quantum dots/silver-based metal-organic framework composites (Ag-MoFs-NCDs and Ag-MoFs-SCDs), which previously showed high antibacterial activity [2], without and with laser light. Firstly, we have found the most convenient and effective CW laser intensity (16 mW/cm2) and illumination time (3 minutes), which is not too high and short enough to influence human cells' proliferation and metabolism positively. Additional chemical treatment with Ag-MoFs-NCDs and Ag-MoFs-SCDs results in a further increase in human cell viability. Our measurements showed that the proliferation index in laser-illuminated cells and cells treated with Ag-MoFs-SCDs was at the level of the untreated control. Furthermore, Ag-MoFs-SCDs treatment and laser illumination induced a mild, insignificant increase in cellular proliferation. On the other hand, Ag-MoFs-NCDs treatment led to a more pronounced, albeit not significant increase, in cellular proliferation, while Ag-MoFs-NCDs treatment combined with laser illumination significantly increased proliferation. Also, we have detected a mild change in collagen level estimated by hydroxyproline assay, which may indicate a positive outcome of combined laser illumination and treatment, taking into account that after 48 hours, a change in cell's response to the treatment could be noticed. Finally, based on migration ass

Carbon Dots (CDs) are biocompatible, fluorescent, water-soluble, and stable nanoparticles with a high potential to be used for vast biomedical applications [1,2]. We explore the application of CDs produced from natural sources, black carrots, as anti-cancer and imaging agents. These nanoparticles suppress cell growth of three different cancer cell lines, cervical (HeLa), pancreatic (PANC-1), and melanoma (A375) cell lines in vitro. However, the cytotoxic effect against A375 cells stands out, with only 20% of viable cells left after treatment (Fig.1(a)), antimetastatic potential, and a selectivity index higher than two, which indicates that the efficacy against melanoma cells is significantly greater than the toxicity against non-malignant cells (MRC-5). Furthermore, after the cellular uptake, green fluorescence was visible in the cytosol of A375 cells (Fig. 1 (b)). On the other hand, the DAPI stain for DNA was visible as a blue light in the cell nucleus. Moreover, cells with a higher intensity of green fluorescence in the nucleus, Fig. 1 (c) indicated with arrows, were the cells with condensed chromatin in the mitotic phase of the cell cycle (Fig. 1 (d) and (e)), which indicates that CDs interact with chromatin and that they could be used as a marker of cells mitosis and proliferation. In summary, we have demonstrated the great anti-cancer potential of black carrot CDs, for image-guided anti-cancer therapy of melanoma that can be used to recognize cell proliferation.

In this work, we have applied the Informational Spectrum Method (ISM) to discover a potential protein target in the HeLa cervical cancer cell line for [Pd(dach)Cl2] complex. Since Pd complexes are considered an alternative to traditionally used Pt complexes in anti-cancer therapy, it is essential to elucidate the mechanism of their action. A detailed analysis that also involves screening the known protein databases revealed the proteins of the SOSS complex as the most probable [Pd(dach)Cl2] targets. Since this protein maintains genomic stability, this result shows the potential of the Pd(II) complex as an anti-cancer drug.

In this work, the performances of two ionic liquid matrices (ILMs) with the same ammonium counterpart for mass spectrometric analysis of the insoluble and soluble sucralfate were compared. Matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) was performed assisted by the butylammonium salts of α-cyano-hydroxycinnamic acid (CHCAB) and 2,5-dihydroxybenzoic acid (DHBB). CHCAB has a higher IE than DHBB, but better optical properties. CHCAB is more suitable for the analysis of sucralfate, although molecular ions of both compounds were detectable only with low intensities. Thus, optical properties of ILMs are crucial to enhance the sensitivity of MALDI MS detection of polysulfated oligosaccharides. © 2019, © 2019 Taylor & Francis Group, LLC.

INTRODUCTION: Matrix-assisted laser desorption and ionization mass spectrometry (MALDI MS) is suitable for clinical applications because of its performances. On the other hand, if organic matrices are used, analysis of small molecules (mass <1000 Da) becomes difficult due to a high number and intensity of matrix –related signals. Certain physiologically important molecules, such as hormones, carbohydrates, drugs, and others, belong to the small molecule group. Application of TiO2 nanoparticles as substrates for surface-assisted laser desorption and ionization (SALDI) MS is, in these cases, promising tool. OBJECTIVES: To test the suitability of TiO2 nanoparticles with various sizes and shapes as substrates for SALDI MS of various classes of small biologically-relevant molecules. METHODS: The following TiO2 nanoparticles are prepared: colloidal nanoparticles (NPs, round, diameters of 5 nm), prolate nanospheroids (PNSs, 40-50 nm length) and nanotubes (NTs, approximately 100 nm long, 10 nm diameter). Samples (amino acids, steroid hormons, vitamins, carbohydrates) at various concentration were analyzed in positive and negative mode, whereas reproducibility and day-to-day repeatability was tested by ANOVA statistical analysis. RESULTS: By tested organic matrices, 63% of samples could not be detected, whereas by using any of nanoparticles, only 33% of analytes were not detectable. The spectra acquired with TiO2 nanoparticles, were characterized by lower number of well defined signals, which did not overlap with the signals from analytes. Analyte signals are simple, and the number of analyte-generated adducts is low when TiO2 substrates are used. Moreover, in some cases, also molecular ions could be detected. Generally, spectra were better reproducible when acquired with nanoparticles compared to organic matrices, as judged by the standard deviations in the signal-to-noise ratio (standard deviations are smaller when nanoparticles are used). In that sense, PNSs demonstrated

MALDI TOF (Matrix-Assisted Laser Desorption and Ionization Time-Of-Flight) mass spectrometry is soft ionization technique. In order to prevent/reduce fragmentation of analyzed molecules, induced with direct excitation with laser, samples are mixed with matrix molecules. Matrix has high absorption coefficient in the range of the laser emission. In spite of numerous advantages, there are serious drawbacks of the matrices, especially for the analysis of molecules with low molecular mass (above 1000 Da). In this group of molecules there are various biologically active molecules, so there is a great need to overcome disadvantages of the application of organic matrices. Several alternative approaches have been developed: an organicmatrix-free approach in which the substrates, usually nanoparticles act as a matrix. The term SALDI (Surface-Assisted Laser Desorption and Ionization) was coined to designate the techniques that use nanostructured substrates. Nanoparticles absorb the laser energy and then rapidly transfer to analyzed molecule. Titanium (IV)-oxide (TiO2) is considered to be a good candidate for SALDI substrate since it is readily available, chemically stable, non-toxic and inexpensive material. TiO2 is a semiconductor with high absorptivity of UV light of nitrogen laser (have a large band gap 3.2 eV) which is used in MALDI TOF mass spectrometry, but the method of synthesis of TiO2 nanocrystal have a great impact on absorption because this phenomenon depends on size, shape and composition of nanoparticles. The applicability of TiO2 nanocrystals of different size and shape was tested. Colloidal TiO2 nanoparticles, TiO2 prolate nanospheroids and TiO2 nanotubes were used as substrates for potential SALDI TOF MS quantitative analysis of biologically active molecules with small molecule mass. First step to test efficiency of TiO2 nanocrystal for the mass spectrometry analysis of small molecules was to examine their qualitative characteristics as substrates. It is shown

Izvod: MALDI TOF (Matrix Assisted Laser Desorption and Ionization Time-Of-Flight) masenaspektrometrija je meka jonizaciona tehnika koja se prvenstveno koristi za analizubiomolekula (proteina i nukleinskih kiselina) i omogućava detekciju molekula uzveoma nizak stepen fragmentacije. Kako bi se sprečila/ublažila fragmentacijaizazvana direktnom ekscitacijom laserom, uzorak se meša sa matricama koje imajuvisok apsorpcioni koeficijent u oblasti u kojoj laser emituje. Primarno su sekoristile organske, „tradicionalne“ matrice. Pored brojnih prednosti, organskematrice pokazuju i značajne mane koje onemogućavaju primenu MALDI masenespektrometrije za kvantitativnu analizu molekula i sprečavaju detekciju molekulamalih masa manjih od 1000 Da. Kako se u ovoj grupi molekula nalaze i različitibiološki značajni molekuli (metaboliti) postoji potreba za prevazilaženjemnedostataka organskih matrica.Jedan od najranije primenjenih načina je zamena organskih matrica neorganskimjedinjenjima i/ili nanočesticama (supstratima). Koriste se različiti supstrati nabazi ugljeničnih polimera i sol-gel polimerne strukture na bazi silicijum dioksida.Upotreba nanostrukturnih supstrata u metodi koja je nazvana SALDI (Surface AssistedLaser Desorption and Ionization) u poslednjoj deceniji je predmet velikog brojapublikovanih radova. Međutim, nanočestice od metala i oksida metala, kao što su Au,Pt, Ag, ZnO, Fe i MnO2/MnO3, nude prednost u odnosu na ostale materijale - stabilnijesu u vazduhu i poseduju visoku provodljivost. Prednost nanočestica je apsorpcijaenergije lasera i efikasan prenos energije do uzorka. Istakle su se nanočestice odtitan(IV)-oksida zbog svoje dostupnosti, netoksičnosti i niske cene, što je takođepredmet mnogih publikovanih radova. Osim navedenih osobina, titan(IV)-oksid jepoluprovodnik sa dobrom UV apsorpcijom. Generalno, TiO2 snažno apsorbuje UVsvetlost (ima znatnu širinu energetske barijere, 3,2 eV) azotnog lasera koji se koristiu MALDI TOF masenoj spektrometriji, ali proces pripre, Summary:MALDI TOF (Matrix-Assisted Laser Desorption and Ionization Time-Of-Flight) massspectrometry is soft ionization technique. Primarily, this technique was used for the analysis ofbiomolecules such as proteins and nucleic acids with low level of their fragmentation. In orderto prevent/reduce fragmentation of analyzed molecules, induced with direct excitation withlaser, samples are mixed with matrix molecules. Matrix has high absorption coefficient in therange of the laser emission. In spite of numerous advantages, there are serious drawbacks ofthe matrices, and because of that they cannot be used for quantitative MALDI massspectrometric analysis and for the detection of small molecules (molecular mass less than 1000Da). In this group of molecules (mass less than 1000 Da) there are various biologically activemolecules (metabolites), so there is a great need to overcome disadvantages of the applicationof organic matrices.Considerable efforts have been made to overcome the above mention problems andseveral alternative approaches have been developed: an organic-matrix-free approach in whichthe substrates, usually nanoparticles act as a matrix. Many are in use: graphite, silica gel, carbonpowder, activated carbon, graphene, porous silicon, and many more.The term SALDI (Surface-Assisted Laser Desorption and Ionization) was coined todesignate the techniques that use nanostructured substrates. The use of various nanoparticlesas substrates in SALDI MS has attracted a lot of attention in the last decade. Nanoparticlesabsorb the laser energy and then rapidly transfer to analyzed molecule. However, the substratesprepared from materials based on metal-oxides (Аu, Pt, Ag, ZnO, Fe and MnO2/MnO3) aremore stable in the air and have a high conductivity. Titanium(IV)-oxide (TiO2) is consideredto be a good candidate for SALDI substrate since it is readily available, chemically stable, nontoxicand inexpensive material. Titanium(IV)-oxide is a semiconductor with high absorptivityof U

Izvod: MALDI TOF (Matrix Assisted Laser Desorption and Ionization Time-Of-Flight) masena spektrometrija je meka jonizaciona tehnika koja se prvenstveno koristi za analizu biomolekula (proteina i nukleinskih kiselina) i omogućava detekciju molekula uz veoma nizak stepen fragmentacije. Kako bi se sprečila/ublažila fragmentacija izazvana direktnom ekscitacijom laserom, uzorak se meša sa matricama koje imaju visok apsorpcioni koeficijent u oblasti u kojoj laser emituje. Primarno su se koristile organske, „tradicionalne“ matrice. Pored brojnih prednosti, organske matrice pokazuju i značajne mane koje onemogućavaju primenu MALDI masene spektrometrije za kvantitativnu analizu molekula i sprečavaju detekciju molekula malih masa manjih od 1000 Da. Kako se u ovoj grupi molekula nalaze i različiti biološki značajni molekuli (metaboliti) postoji potreba za prevazilaženjem nedostataka organskih matrica. Jedan od najranije primenjenih načina je zamena organskih matrica neorganskim jedinjenjima i/ili nanočesticama (supstratima). Koriste se različiti supstrati na bazi ugljeničnih polimera i sol-gel polimerne strukture na bazi silicijum dioksida. Upotreba nanostrukturnih supstrata u metodi koja je nazvana SALDI (Surface Assisted Laser Desorption and Ionization) u poslednjoj deceniji je predmet velikog broja publikovanih radova. Međutim, nanočestice od metala i oksida metala, kao što su Au, Pt, Ag, ZnO, Fe i MnO2/MnO3, nude prednost u odnosu na ostale materijale - stabilnije su u vazduhu i poseduju visoku provodljivost. Prednost nanočestica je apsorpcija energije lasera i efikasan prenos energije do uzorka. Istakle su se nanočestice od titan(IV)-oksida zbog svoje dostupnosti, netoksičnosti i niske cene, što je takođe predmet mnogih publikovanih radova. Osim navedenih osobina, titan(IV)-oksid je poluprovodnik sa dobrom UV apsorpcijom. Generalno, TiO2 snažno apsorbuje UV svetlost (ima znatnu širinu energetske barijere, 3,2 eV) azotnog lasera koji se koristi u MALDI TOF masenoj spektrom, Summary: MALDI TOF (Matrix-Assisted Laser Desorption and Ionization Time-Of-Flight) mass spectrometry is soft ionization technique. Primarily, this technique was used for the analysis of biomolecules such as proteins and nucleic acids with low level of their fragmentation. In order to prevent/reduce fragmentation of analyzed molecules, induced with direct excitation with laser, samples are mixed with matrix molecules. Matrix has high absorption coefficient in the range of the laser emission. In spite of numerous advantages, there are serious drawbacks of the matrices, and because of that they cannot be used for quantitative MALDI mass spectrometric analysis and for the detection of small molecules (molecular mass less than 1000 Da). In this group of molecules (mass less than 1000 Da) there are various biologically active molecules (metabolites), so there is a great need to overcome disadvantages of the application of organic matrices. Considerable efforts have been made to overcome the above mention problems and several alternative approaches have been developed: an organic-matrix-free approach in which the substrates, usually nanoparticles act as a matrix. Many are in use: graphite, silica gel, carbon powder, activated carbon, graphene, porous silicon, and many more. The term SALDI (Surface-Assisted Laser Desorption and Ionization) was coined to designate the techniques that use nanostructured substrates. The use of various nanoparticles as substrates in SALDI MS has attracted a lot of attention in the last decade. Nanoparticles absorb the laser energy and then rapidly transfer to analyzed molecule. However, the substrates prepared from materials based on metal-oxides (Аu, Pt, Ag, ZnO, Fe and MnO2/MnO3) are more stable in the air and have a high conductivity. Titanium(IV)-oxide (TiO2) is considered to be a good candidate for SALDI substrate since it is readily available, chemically stable, nontoxic and inexpensive material. Titanium(IV)-oxide is a semiconductor wit

This paper presents optimization of matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF) mass spectrometer (MS) instrumental parameters for the analysis of chloro(2,2 , 2 -terpyridine) palladium(II) chloride dihydrate complex applying design of experiments methodology (DoE). This complex is of interest for potential use in the cancer therapy. DoE methodology was proved to succeed in optimization of many complex analytical problems. However, it has been poorly used for MALDI-TOF-MS optimization up to now. The theoretical mathematical relationships which explain the influence of important experimental factors (laser energy, grid voltage and number of laser shots) on the selected responses (signal to noise - S/N ratio and the resolution - R of the leading peak) is established. The optimal instrumental settings providing maximal S/N and R are identified and experimentally verified.

In this work it has been shown that both the laser desorption/ionization mass spectrometry (LDI MS) and the matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI TOF MS) are the simple and quick methods for determination of relative natural isotopic distribution of lead. The analysis of metal salts with these approaches does not require any time-consuming preparation of samples: a single run can take only a minute, and numerous information can be obtained. Results obtained in this work show that chosen matrix has no negative effect on quantitative determination of lead isotopes and support once more the applicability of MALDI TOF MS for lead isotope distribution determination in the sample and accurate data are obtained. Additionally, the generation of PbnOn and PbnOn-1 (n: 2-6) clusters have been successfully achieved in the positive mode, using the both LDI and MALDI methods. All stoichiometries were confirmed using isotopic pattern modelling.

We studied the colloidal TiO2 nanoparticles as a carrier for controlled delivery of the ruthenium complex to the melanoma cell line. The system demonstrated slower complex release upon visible and increased release rate upon UV light illumination. Accordingly, the light-dependent cytotoxicity of the system was demonstrated on amelanotic melanoma cancer line. The cell death is enhanced by UV and reduced by red light in the presence of investigated nanocomposite system. Both components of the system may act as photosensitizers, by generating reactive oxygen species, which promote cell death. Thus, the system might act dually, as photodynamic therapeutic agent and as the light tunable system for metallo-drug delivery and it might be of interest for development of new more efficient drug delivery approaches by using a light as external stimulus. (C) 2017 Elsevier B.V. All rights reserved.

Approximately 13 million of new cancer cases are diagnosed every year, and the mortality rate is projected to rise, with an estimation of 13.1 million deaths in 2030 [1]. The conventional cancer treatments such as chemotherapy, radiotherapy and surgery suffer from serious drawbacks that hamper patients’ healing and recovery: radiation therapy is limited by the cumulative radiation dose,chemotherapy is frequently associated with systemic side-effects, while rather high recurrence rate is associated with surgical resection of tumors. Photodynamic therapy, which implies combined use of a photosensitising medicament and low-intensity light to cause selective damage to the target tissue, is an alternative tumor-ablative, function-sparing and costeffective oncologic approach [2]. Usually, medicaments are delivered to diseased tissues by different types of nanoparticle (NP) carriers. The light-induced medicament activation is based on the intrinsic optical properties of a medicament carrier and a medicament itself. In most cases, a NP-based medicament carrier or a medicament itself acts as photosensitizers [PSs], by triggering the free radical reactions in cells leading eventually to the cell death. The most PSs are characterized by high lipophilicity, and due to that, different encapsulation strategies have been explored to protect the hydrophobic PS from the aqueous environment. We used TiO2 NPs for medicament carriers because of their availability, non-toxicity, stability and possibility of surface modification. On the other hand, Ru(II)(dcbpy)2Cl2 complex, that belongs to the second generation of metallodrugs, can be easily attached to the TiO2 surface via carboxyl groups [3], while central metal ion remains free for the interaction with biomolecules. Additionally, this system has genotoxic effect on melanoma cells [4]. The aim of the present study was to modify the nanocomposite system (NCS) based on the Ru complex and TiO2 NPs in order to increase the cellular uptake

U ovom radu, matematička metoda Dizajn eksperimenta (eng. Design of Experiment, DoE) korišćena je za optimizaciju instrumetalnih parametara masenog spektrometra sa laserskom desorpcijom i jonizacijom pomoću „matriksa“ i sa analizatorom na bazi vremena preleta (MALDI TOF MS), a za analizu metalnih kompleksa. Ulazni parametri DoE metodologije bili su intenzitet lasera, napon na „gridu“ i broj impulsa lasera, dok su kao izlazni parametri od interesa bili odnos signal/šum i rezolucija. Različite vrednosti ulaznih parametra (njihovi nivoi) definisane su na osnovu dobijenih preliminarnih eksperimenata. Nakon utvrđivanja ulaznih i izlaznih parametara DoE eksperiment je izveden primenom Box-Behnken-ove metode. Teorijski predviđene vrednosti za dobijanje kvalitetnog masenog spektra metalnog kompleksa (snaga lasera-1220 W, napon „grida“-79 V i broj impulsa lasera-360) su eksperimentalno potvrđeni., In this work Design of Experiment mathematical methodology (DoE) was used for optimization the instrumental parameters of matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF) mass spectrometer (MS) for the analysis of metal complex. The input factors in DoE methodology were laser intensity, grid voltage and number of laser shots, while the output response of interest were signal-to-noise ratio and resolution. The different values of input factors (their level) are defined according to the results obtained in preliminary experiments. After the identification of input factors and responses of interest the DoE experimental plan is created using Box-Behnken methode. Theoretically predicted values for obtaining high-quality mass spectra of metal complex (laser power – 1220 W, grid voltage – 79 V and number of laser shots – 360) are experimentally confirmed.

U ovom radu, matematička metoda Dizajn eksperimenta (eng. Design of Experiment, DoE) korišćena je za optimizaciju instrumetalnih parametara masenog spektrometra sa laserskom desorpcijom i jonizacijom pomoću „matriksa“ i sa analizatorom na bazi vremena preleta (MALDI TOF MS), a za analizu metalnih kompleksa. Ulazni parametri DoE metodologije bili su intenzitet lasera, napon na „gridu“ i broj impulsa lasera, dok su kao izlazni parametri od interesa bili odnos signal/šum i rezolucija. Različite vrednosti ulaznih parametra (njihovi nivoi) definisane su na osnovu dobijenih preliminarnih eksperimenata. Nakon utvrđivanja ulaznih i izlaznih parametara DoE eksperiment je izveden primenom Box-Behnken-ove metode. Teorijski predviđene vrednosti za dobijanje kvalitetnog masenog spektra metalnog kompleksa (snaga lasera-1220 W, napon „grida“-79 V i broj impulsa lasera-360) su eksperimentalno potvrđeni., In this work Design of Experiment mathematical methodology (DoE) was used for optimization the instrumental parameters of matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF) mass spectrometer (MS) for the analysis of metal complex. The input factors in DoE methodology were laser intensity, grid voltage and number of laser shots, while the output response of interest were signal-to-noise ratio and resolution. The different values of input factors (their level) are defined according to the results obtained in preliminary experiments. After the identification of input factors and responses of interest the DoE experimental plan is created using Box-Behnken methode. Theoretically predicted values for obtaining high-quality mass spectra of metal complex (laser power – 1220 W, grid voltage – 79 V and number of laser shots – 360) are experimentally confirmed.

Lečenje kancera u današnje vreme uključuje primenu različitih terapija koje se uglavnom zasnivaju na primeni kompleksa prelaznih metala. Kada se razmatraju nove strategije u lečenju kancera, ističe se fotodinamička terapija. Ovaj vid terapije koristi svetlo kao aktivator leka ili nosača leka na mestu obolelog tkiva. Uzimajući u obzir navedeno, testirali smo potencijal prethodno sintetisanog fotoaktivnog nanokompozitnog sistema i njegovih komponenti za primenu u fotodinamičkoj terapiji. Pomenuti sistem se sastoji od nanočestica TiO2 kao nosača leka i kompleksa [Ru(II)(dcbpy)2Cl2], kao potencijalnog citostatika, vezanog za površinu nanočestica. Rutenijumov kompleks iskazuje svoje citotosično delovanje vezivanjem za ciljne biomolekule, dok dosač, TiO2, vezujući kompleks može smanjiti njegovu reaktivnost sa zdravim ćelijama dok ne dođe do tumorskog tkiva. Pomenuti nanokompozitni sistem i njegove komponente su testirane na ćelijama melanoma. Rezultati ukazuju na to da dejstvom UV svetla, nakon tretmana sa obe komponente sistema (kompleksom i TiO2) dolazi do značajnog smanjenja u broju tumorskih ćelija, dok je nanokompozitni sistem pokazao sinergistički efekat i dovodio do smanjenja broja tumorskih ćelija ispod 50%. Stoga, ovaj sistem ostavlja mesta za dalja izučavanja jer pruža mogućnost razvoja efiksnije terapije u kojoj bi doziranje leka bilo kontrolisanano svetlom., The treatment of cancer involves different therapies mainly based on transition metal complexes. When exploring new strategies for the treatment of cancer, one possibility is the use of photodynamic therapy. Photodynamic therapy utilizes light to activate a drug or a drug/carrier system when they are localized in the tumor tissue. Therefore, we have tested the potential of previously synthesized photoactive nanocomposite system and its components as a candidate for photodynamic therapy. The nanocomposite system consists of TiO2 nanoparticles as drug/carrier and ruthenium.complex [Ru(II)(dcbpy)2Cl2] bound to its surface as a potential antitumor drug. This Ru complex have been shown to exert cytotoxic effect through binding to target biomolecules, while TiO2 carrier can serve to minimize side reactivity in the bloodstream and healthy cells until it reaches tumor cells. The nanocomposite system and its components are successfully applied on melanoma tumor cell lines. It was demonstrated that the illumination by UV light, after treatment either with Ru-complex or TiO2 nanoparticles significantly decreases melanoma cell survival rate, while NCS shown synergistic effect and have reduced the number of melanoma cells under 50%. Hence, this system might be of interest from the standpoint of development of more efficient, light controllable drug delivery approaches.