Publicação
Development and characterization of a mixed polymeric micelle as a potential therapeutic strategy for osteosarcoma
| Resumo: | Osteosarcoma (OS) is a rare and aggressive bone tumor that impacts mostly children and young adults. In spite of the numerous efforts made to date in the therapeutic field, OS still presents a low patient survival rate, high metastasis and relapse occurrence, mostly due to multidrug resistant cells. To surpass that, nanomedicine has been extensively investigated for the targeted delivery of genetic material, drugs or both. Polymeric micelles (PM) are nanosystems that facilitate the targeted transportation of poorly water-soluble drugs to cancer cells. These nanocomposites are composed of amphiphilic block copolymers, such as poloxamers, or Pluronics®, that self-assemble into a micellar structure when in contact with an aqueous solution. Pluronics® F68 and P123 are widely used poloxamers in the pharmaceutical area due to their advantageous characteristics. A micelleplex is formed from the conjugation of amphiphilic copolymer(s), a cationic polymer, linked to genetic material and/or drugs. This is because the cationic property will allow for the transportation of nucleic acids and thus, the possibility for a dual therapy. Cationic polymers can be of natural or synthetic origin, such as chitosan or polyethyleneimine (PEI), respectively.miRNAs have been implicated as participators in the development, metastasis and progression of OS. miRNA-145 is underexpressed in this disease and associated with a worse cancer prognosis. We hypothesize that the delivery of miRNA-145 to OS cells via a micelleplex, composed of Pluronic® F68 and either chitosan or PEI, will be able to inhibit tumor proliferation and migration.In this present work, we aim to elucidate the application of a micelleplex encapsulating miRNA-145 in order to achieve a targeted delivery to OS cells and overcome multidrug resistance, as a new and viable treatment option. As such, we have developed and optimized a mixed PM consisting of Pluronics® P123 and F68 complexed with PEI. |
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| Autores principais: | Melim, Catarina Pereira |
| Assunto: | Osteossarcoma Micelas Poliméricas miRNA-145 Pluronic® F68 Pluronic® P123 Osteosarcoma Polymeric Micelles miRNA-145 Pluronic® F68 Pluronic® P123 |
| Ano: | 2020 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso embargado |
| Instituição associada: | Universidade de Coimbra |
| Idioma: | inglês |
| Origem: | Estudo Geral - Universidade de Coimbra |
| Resumo: | Osteosarcoma (OS) is a rare and aggressive bone tumor that impacts mostly children and young adults. In spite of the numerous efforts made to date in the therapeutic field, OS still presents a low patient survival rate, high metastasis and relapse occurrence, mostly due to multidrug resistant cells. To surpass that, nanomedicine has been extensively investigated for the targeted delivery of genetic material, drugs or both. Polymeric micelles (PM) are nanosystems that facilitate the targeted transportation of poorly water-soluble drugs to cancer cells. These nanocomposites are composed of amphiphilic block copolymers, such as poloxamers, or Pluronics®, that self-assemble into a micellar structure when in contact with an aqueous solution. Pluronics® F68 and P123 are widely used poloxamers in the pharmaceutical area due to their advantageous characteristics. A micelleplex is formed from the conjugation of amphiphilic copolymer(s), a cationic polymer, linked to genetic material and/or drugs. This is because the cationic property will allow for the transportation of nucleic acids and thus, the possibility for a dual therapy. Cationic polymers can be of natural or synthetic origin, such as chitosan or polyethyleneimine (PEI), respectively.miRNAs have been implicated as participators in the development, metastasis and progression of OS. miRNA-145 is underexpressed in this disease and associated with a worse cancer prognosis. We hypothesize that the delivery of miRNA-145 to OS cells via a micelleplex, composed of Pluronic® F68 and either chitosan or PEI, will be able to inhibit tumor proliferation and migration.In this present work, we aim to elucidate the application of a micelleplex encapsulating miRNA-145 in order to achieve a targeted delivery to OS cells and overcome multidrug resistance, as a new and viable treatment option. As such, we have developed and optimized a mixed PM consisting of Pluronics® P123 and F68 complexed with PEI. |
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