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Author Arranz Fíguls, Clara |
Abstract Lung cancer is the most common cause of cancer-related death around the world, with over 1.8 million deaths yearly. Despite advances in the treatment during the last decades, long-term survival rates remain poor. Cytotoxic chemotherapy is one of the main treatments used, however, its indiscriminate toxicity towards cancer and normal tissues limits its effectiveness. These deficiencies have encouraged the development of novel and more efficient tumor-targeted therapeutic strategies. In this study, mesoporous silica nanoparticles (MSNs) gated with peptide nucleic acids (PNA) for lung cancer treatment were synthesized and characterized. Two materials were prepared and loaded with the dye safranin O (CA002) and the drug camptothecin (CA007). The nanoparticles were subjected to an initial surface modification with thiol groups using 3-mercaptopropyl trimethoxysilane (MPTMS) and then, thiol-yne click chemistry was employed to graft PNA to the surface of the MSNs. Adenine trimer with a linker composed of multiple units of 5-hexynoic acid was chosen as PNA sequence and its structure was confirmed by HPLC. The proper loading and functionalization with PNA was verified through a detailed characterization of the materials by standard techniques. Typical hexagonal arrangement of mesopores with mean diameters bellow 100 nm and a slightly increase in size in PNA-functionalized nanomaterials was noticed. Moreover, upon loading and functionalization steps there was a progressive decrease in surface area and pore volume. Energy-dispersive X ray spectroscopy revealed atomic ratios of 2:1 for O/Si confirming the polymerization of SiO2 units and the presence of sulfur, nitrogen and carbon, coming from thiols, the encapsulated cargo and PNA, respectively. FTIR spectrums verified the chemical structures of the synthetized nanoparticles. In vitro cargo release studies showed negligible safranin liberation in CA002SAF-PNA and CA002SAF-PNA+T attributed to the loss of safranin during the washings. Bulky molecular gates formed by PNA-adenine trimer complexed with thymine units by hydrogen bonds could have been closing more the pores at neutral pH in comparison with gatekeepers without thymine monomers. Regarding CA007 nanomaterials, PNA-functionalization favour the release of the drug at pH corresponding to tumor microenvironment (pH 5). Previous hypothesis of PNA-T gates was not applicable in this case, as addition of thymine at neutral pH did not promote the closing of the pores. Excess of drug added during CA007CPT-PNA-T synthesis could be the reason for the higher liberation. Different responses were exhibited in both nanoparticles (CA002 and CA007), hence, further experiments will have to be performed in order to establish more consistent statements. |
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Director Fornaguera Puigvert, Cristina |
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Degree IQS SE - Undergraduate Program in Biotechnology |
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Date 2021-09-07
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