Browsing by Author "Soto-Arriaza, Marco"

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    Increased delivery and cytotoxicity of doxorubicin in HeLa cells using the synthetic cationic peptide pEM-2 functionalized liposomes
    (2023) Salas Sanzana, Diego; Flores Faundez, Emilia; Melendez, Jaime; Soto-Arriaza, Marco
    Hypothesis: Due to the inability of nano-carriers to passively cross the cell membrane, cell penetration enhancers are used to accelerate cytoplasmic delivery of antineoplastic drugs. In this regard, snake venom phospholipase A2 peptides are known for their ability to destabilize natural and artificial membranes. In this context, function-alized liposomes with peptide pEM-2 should favor the incorporation of doxorubicin and increase its cytotoxicity in HeLa cells compared to free doxorubicin, and doxorubicin encapsulated in non-functionalized liposomes.Experiments: Several characteristics were monitored, including doxorubicin loading capacity of the liposomes, as well as the release and uptake before and after functionalization. Cell viability and half-maximal inhibition concentrations were determined in HeLa cells. Findings: In vitro studies showed that functionalization of doxorubicin-loaded PC-NG liposomes with pEM-2 not only improved the amount of doxorubicin delivered compared to free doxorubicin or other doxorubicin-containing formulations, but also showed enhanced cytotoxicity against HeLa cells. The PC-NG liposomes loaded with doxorubicin improved treatment efficacy by reducing the IC50 value and incubation time. This in-crease in cell toxicity was directly related to the concentration of pEM-2 peptide bound to the liposomes. We conclude that the cytotoxicity observed in HeLa cells due to the action of doxorubicin was strongly favored when encapsulated in synthetic liposomes and functionalized with the pEM-2 peptide.
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    Supramolecular complex of tetracationic porphyrin with acyclic cucurbituril-like container induces quantitative singlet oxygen generation. Phototoxicity studies in vitro in MCF-7 human breast cancer cells
    (2024) Day, Skarlett; Pérez, Benjamín; Guerra Díaz, Daniel; Mariño-Ocampo, Nory; Zúñiga-Núñez, Daniel; Faúndez, Mario A.; Soto-Arriaza, Marco; Pizarro, Nancy; Heyne, Belinda; Fuentealba, Denis
    Singlet oxygen generation by porphyrin-based photosensitizers is one of the main strategies used in the photodynamic therapy of cancerous lesions. In this work, we report that the complexation of tetracationic 5,10,15,20-tetrakis(N-methylpiridinium-4-yl)porphyrin (TMPyP) with an acyclic cucurbituril-like container denominated M2C4 achieves quantitative generation of singlet oxygen. The complexation was studied by isothermal titration calorimetry, revealing a highly favored binding event controlled by enthalpic contributions, a stoichiometry of 1:1 and a high binding constant (K = (1.7 ± 0.2) × 107 M−1). Photophysical studies of the complex showed bathochromic shifts in the absorption bands, increased fluorescence emission quantum yield and lengthened fluorescence lifetime. Nonetheless, fluorescence emission was minor, being intersystem crossing with the consequent generation of singlet oxygen the main deactivation pathway for the excited state. All these properties were compared with the previously reported TMPyP and cucurbit[7]uril (CB[7]) complex, which showed a superiority of the acyclic complex in terms of quantum efficiencies. Phototoxicity studies in a breast cancer cell line (MCF-7) cultured in vitro, showed that the TMPyP@M2C4 complex is unable to enter the cells even after a 24 h incubation period. However, this issue could be circumvented by encapsulating the complex into liposomes which delivered the complex to the cells efficiently. Overall, this strategy showed good potential for a highly efficient photodynamic treatment using the TMPyP@M2C4 complex in liposomal formulations.