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Preparation and characterization of gadolinium-based thermosensitive liposomes: A potential nanosystem for selective drug delivery to cancer cells

2021; Elsevier BV; Volume: 65; Linguagem: Inglês

10.1016/j.jddst.2021.102686

2588-8943

Ana Luiza Chaves Maia, Aline T. M. e Silva, Aina Liz Alves César, Cristiane dos Santos Giuberti, Fernanda Cristina Gontijo Evangelista, Janaína de Alcântara Lemos, Adriano de Paula Sabino, Ângelo Malachias, Christian Fernandes, André Luís Branco de Barros, Daniel Crístian Ferreira Soares, Gilson Andrade Ramaldes,

Advanced biosensing and bioanalysis techniques

Gadodiamide (Gd-DTPA-BMA) is a gadolinium-based complex, used as a contrast agent in magnetic resonance imaging procedures. Recent studies revealed the capacity of this complex of inducing apoptosis in neoplastic cells. However, a great challenge for its use as an anticancer drug is low cellular internalization and drug delivery systems such as thermosensitive liposomes can be a strategy to overcome these limitations and increase anti-tumor efficacy. In this context, this study aimed to develop, characterize, and assess the cytotoxic activity and selectivity index of thermosensitive liposomes containing Gd-DTPA-BMA. Formulations were prepared by the lipid film hydration method and their physicochemical, morphological, and thermal properties were evaluated. Cell viability was performed 4T1/MDA-MB-231 tumor cells and WI-26 VA4 normal cells. Transmission electron microscopy analyses showed high electron density in the inner core of Gd-DTPA-BMA-loaded liposomes that can be attributed to the Gd-DTPA-BMA, since Gd-loaded nanosystems present low light transmittance and high electron density by this technique. The dynamic light scattering, differential scanning calorimetry, small-angle X-ray scattering, and in vitro release results confirm that the lipid composition was suitable since Tc (temperature of the transition Lβ → Lα) values are in accordance with those reported for thermosensitive liposomes used in the treatment of cancer. The cytotoxic studies against breast cancer cell lines demonstrated that the Gd-DTPA-BMA-loaded liposomes have higher cytotoxicity than free Gd-DTPA-BMA. Moreover, these liposomes presented minimal toxicity in a normal cell line when compared to the free Gd-DTPA-BMA. Therefore, the results of this study suggest that thermosensitive liposomes containing Gd-DTPA-BMA might be a new promising nanocarrier system for breast cancer treatment.