Copper (II) Metallodendrimers Combined with Pro-Apoptotic siRNAs as a Promising Strategy Against Breast Cancer Cells

Cancer treatment with small interfering RNA (siRNA) is one of the most promising new strategies; however, transfection systems that increase its bioavailability and ensure its delivery to the target cell are necessary. Transfection systems may be just vehicular or could contain fragments with anticancer activity that achieves a synergistic effect with siRNA. Cationic carbosilane dendrimers have proved to be powerful tools as non-viral vectors for siRNA in cancer treatment, and their activity might be potentiated by the inclusion of metallic complexes in its dendritic structure. We have herein explored the interaction between Schiff-base carbosilane copper (II) metallodendrimers, and pro-apoptotic siRNAs. The nanocomplexes formed by metallodendrimers and different siRNA have been examined for their zeta potential and size, and by transmission electron microscopy, fluorescence polarisation, circular dichroism, and electrophoresis. The internalisation of dendriplexes has been estimated by flow cytometry and confocal microscopy in a human breast cancer cell line (MCF-7), following the ability of these metallodendrimers to deliver the siRNA into the cell. Finally, in vitro cell viability experiments have indicated effective interactions between Cu (II) dendrimers and pro-apoptotic siRNAs: Mcl-1 and Bcl-2 in breast cancer cells. Combination of the first-generation derivatives with chloride counterions and with siRNA increases the anticancer activity of the dendriplex constructs and makes them a promising non-viral vector.Polish National Agency for Academic Exchange (NAWA)European CommissionMinisterio de Economía y CompetitividadComunidad de MadridJunta de Comunidades de Castilla-La Manch

In Vitro anticancer properties of copper metallodendrimers

Newly synthesized carbosilane copper dendrimers (CCD) with chloride and nitrate surface groups seem to be good candidates to be used as gene and drug carriers in anti-cancer therapy, due to their properties such as size and surface charge. Copper attached to the nanoparticles is an important element of many biological processes and recently their anti-cancer properties have been widely examined. Zeta size and potential, transmission electron microscopy (TEM), circular dichroism (CD), analysis of haemolytic activity, and fluorescence anisotropy techniques were used to characterize copper dendrimers. Additionally, their cytotoxic properties toward normal (PBMC) and cancer (1301; HL-60) cells were examined. All tested dendrimers were more cytotoxic against cancer cells in comparison with normal cells

Lipid-coated ruthenium dendrimer conjugated with doxorubicin in anti-cancer drug delivery: Introducing protocols

One of the major limitations for the treatment of many diseases is an inability of drugs to cross the cell membrane barrier. Different kinds of carriers are being investigated to improve drug bioavailability. Among them, lipid or polymer-based systems are of special interest due to their biocompatibility. In our study, we combined dendritic and liposomal carriers and analysed the biochemical and biophysical properties of these formulations. Two preparation methods of Liposomal Locked-in Dendrimers (LLDs) systems have been established and compared. Carbosilane ruthenium metallodendrimer was complexed with an anti-cancer drug (doxorubicin) and locked in a liposomal structure, using both techniques. The LLDs systems formed by hydrophilic locking had more efficient transfection profiles and interacted with the erythrocyte membrane better than systems using the hydrophobic method. The results indicate these systems have improved transfection properties when compared to noncomplexed components. The coating of dendrimers with lipids significantly reduced their hemotoxicity and cytotoxicity. The nanometric size, low polydispersity index and reduced positive zeta potential of such complexes made them attractive for future application in drug delivery. The formulations prepared by the hydrophobic locking protocol were not effective and will not be considered furthermore as prospective drug delivery systems. In contrast, the formulations formed by the hydrophilic loading method have shown promising results where the cytotoxicity of LLD systems with doxorubicin was more effective against cancer than normal cells

The Anti Spy and Anti Secret Intelligence System. Module: Secure Smartphone

Na wstępie umieszczamy ogólną analizę tematu projektu, wady i zalety różnych rozwiązań, które możemy zastosować, oraz nasz wybór technologii.W drugim rozdziale omawiamy i wybieramy protokoły kryptograficzne do zastosowania w naszym bezpiecznym komunikatorze. Znajdują się tam algorytmy Diffiego-Hellmana, Double Ratchet, AES, OMEMO. Celem rozdziału trzeciego jest zaproponowanie serwera do bezpiecznej komunikacji. Omawiamy tam technologie takie jak RabbitMQ i ejabberd. Skupiamy się na protokole XMPP. Rozdział czwarty traktuje o aplikacji na Androida, która posłuży nam za bezpieczny komunikator internetowy. Ulepszamy tam istniejące rozwiązanie dostępne na licencji Open Source o nazwie Conversations. W kolejnym, piątym rozdziale prezentujemy sposób w jaki ma miejsce komunikacja między naszymi urządzeniami. Przedstawiamy zasady działania użytych przez nas protokołów oraz serwera i komunikujących się z nim telefonów.W rozdziale szóstym pokazujemy jak utrudnić dostęp do urządzenia przez osoby nieuprawnione, utrudniamy uzyskanie kodu odblokowania ekranu przez podejrzenie wybieranych cyfr na klawiaturze pinpad. Wymuszamy dłuższą minimalną długość hasła i zwiększamy maksymalną długość hasła. Zmniejszamy limit prób odblokowania odciskiem palca.Rozdział siódmy ma formę poradnika, w którym krok po kroku pokazujemy jak można stworzyć środowisko deweloperskie pod rozwój własnej wersji systemu operacyjnego Android. Znajdują się tam sposoby na dodanie własnych aplikacji do naszego zmodyfikowanego systemu. Pokazujemy jak sflashować i uruchomić system na emulatorze i na rzeczywistym smartfonie.W rozdziale ósmym, który jednocześnie jest ostatnim, przedstawiamy dalsze kierunki prac.In the beginning, there is an introduction to the subject of the thesis. We present the advantages and disadvantages of solutions we might apply as well as the choice of technology used. In the second chapter, we are choosing cryptographic protocols for our secure mobile communicator. In this chapter, there are Diffie-Hellman algorithm, Double Ratchet, AES, OMEMO.The point of the third chapter is to propose a safe and secure communication server. We are introducing technologies such as RabbitMQ and ejabberd. Our main focus is on the XMPP protocol. The fourth chapter is about Android application which will serve us as secure and safe internet communicator. In this chapter, we are enhancing the existing Open Source implementation of the Conversations mobile app. In the fifth chapter, we present the way the communication between our devices is done. We are focusing on the details of protocols' implementations, server and smartphones.In the sixth chapter, we present how to prevent unauthorized access to the device. We are introducing pin pad randomization which prevents gaining pin code by looking over someone's shoulder. We enforce the longer minimal length of the password and extend the maximal length of the password. We limit the number of tries to unlock the device by the fingerprint reader.The seventh chapter is structured as a tutorial in which we are showing step by step on how to create a development environment to develop our modification of the Android operating system. In this chapter, we can find different ways to add or remove applications from the system. We are presenting how to flash and run the operating system on an emulator or a true device.The eighth chapter is about further plans for the project