Nanocarreador magnético de hidróxido duplo lamelar para aplicações biomédicas
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Data
2022-07-25
Autores
Pochapski, Daniel José
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Editor
Universidade Estadual Paulista (Unesp)
Resumo
Hidróxidos duplos lamelares (HDL) são uma classe específica de materiais inorgânicos 2D com propriedades físico-químicas versáteis e moduladoras que permitem diversas aplicações biomédicas, como diagnóstico, prevenção e tratamento de doenças. Em particular, as nanopartículas (NP) de HDL mostraram recentemente avanços sem pre-cedentes na construção química controlável e simplificada, engenharia de superfície versátil e pesquisa biológica abrangente. Dentro deste contexto, exploramos neste tra-balho a construção de uma estrutura multifuncional a base de HDL e NP de magnetita (Fe3O4), com potencial aplicação como um nanocarreador magnético para liberação controlada de droga com uso simultâneo na terapia anticâncer da hipertermia do fluido magnético (HFM). Para isso, sintetizamos NP de HDL de ZnAl por uma rota sol-gel modificada e NP de Fe3O4 pelo método de co-precipitação para serem utilizados como blocos de construção coloidal. A estrutura multifuncional é formada através de um pro-cesso de agregação espontâneo, dependente unicamente da magnitude e sinal da carga superficial das NP. Um fármaco modelo (diclofenaco de sódio) foi intercalado na camada interlamelar das NP de HDL para mostrar que a liberação local da droga pode ser desencadeada pela aplicação de um campo magnético alternado (AMF). Além dis-so, o calor gerado pela estrutura automontada quando exposta ao AMF por um tempo (t), é suficientemente alto (>44-46 0C e t 1-5 min) para levar a necrose de um tecido tu-moral. Estes resultados são suportados por simulações numéricas, que demonstraram que o calor gerado durante a hipertermia magnética pode levar a necrose completa de um tumor localizado na glândula mamária. O presente trabalho explora os desafios recentes encontrados no desenvolvimento de novas estruturas multifuncionais a base de HDL para aplicações biológicas, incluindo estabilidade coloidal, acúmulo no local alvo da doença e integração com múltiplas modalidades.
Layered double hydroxides (LDH) are a specific class of 2D inorganic materials with versatile and modulates physicochemical properties that allow for diverse biomedical applications, such as in the diagnosis, prevention, and treatment of diseases. In partic-ular, LDH nanoparticles (LDH NPs) have recently shown unprecedented advances in controllable and simplified chemical construction, versatile surface engineering, and comprehensive biological research. Within this context, we explore in this work the construction of a multifunctional structure based on LDH and magnetite (Fe3O4) NPs, with potential application as a magnetic nanocarrier for controlled drug release with simultaneous use for magnetic fluid hyperthermia (MRM) as an anticancer therapy. For this, we synthesized ZnAl LDH NPs by a modified sol-gel route and Fe3O4 NPs by the co-precipitation method to be used as colloidal building blocks. The automated struc-ture is formed through a spontaneous aggregation process, dependent on the magni-tude and sign of the NPs surface charge. A model drug (diclofenac sodium) was inter-calated into the interlamellar layer of LDH NPs to show that local drug release can be triggered by the application of an alternating magnetic field (AMF). In addition, the heat generated by the self-assembled structure when exposed to the alternating magnetic field for a time (t) is high enough (>44 °C, from t 1-5 min) to lead to the tumor tissue ne-crosis. These results were supported by numerical simulations, which show that the heat generated during magnetic hyperthermia can lead to complete necrosis of a tumor located in the mammary gland. The present work explores recent challenges encoun-tered in the development of new multifunctional LDH -based structures for biological applications, including colloidal stability, accumulation at the disease-targeted site, and integration with multiple modalities.
Layered double hydroxides (LDH) are a specific class of 2D inorganic materials with versatile and modulates physicochemical properties that allow for diverse biomedical applications, such as in the diagnosis, prevention, and treatment of diseases. In partic-ular, LDH nanoparticles (LDH NPs) have recently shown unprecedented advances in controllable and simplified chemical construction, versatile surface engineering, and comprehensive biological research. Within this context, we explore in this work the construction of a multifunctional structure based on LDH and magnetite (Fe3O4) NPs, with potential application as a magnetic nanocarrier for controlled drug release with simultaneous use for magnetic fluid hyperthermia (MRM) as an anticancer therapy. For this, we synthesized ZnAl LDH NPs by a modified sol-gel route and Fe3O4 NPs by the co-precipitation method to be used as colloidal building blocks. The automated struc-ture is formed through a spontaneous aggregation process, dependent on the magni-tude and sign of the NPs surface charge. A model drug (diclofenac sodium) was inter-calated into the interlamellar layer of LDH NPs to show that local drug release can be triggered by the application of an alternating magnetic field (AMF). In addition, the heat generated by the self-assembled structure when exposed to the alternating magnetic field for a time (t) is high enough (>44 °C, from t 1-5 min) to lead to the tumor tissue ne-crosis. These results were supported by numerical simulations, which show that the heat generated during magnetic hyperthermia can lead to complete necrosis of a tumor located in the mammary gland. The present work explores recent challenges encoun-tered in the development of new multifunctional LDH -based structures for biological applications, including colloidal stability, accumulation at the disease-targeted site, and integration with multiple modalities.
Descrição
Palavras-chave
Hidróxidos duplos lamelares, Magnetita, Materiais biomédicos, Métodos de simulação, Hipertermia