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FuncionalizaĆ§Ć£o de nanossistemas com anticorpos monoclonais para o direcionamento ativo: estado da arte
| Name: | Description: | Size: | Format: | |
|---|---|---|---|---|
| 38167 | 1.06 MB | Adobe PDF |
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Advisor(s)
Abstract(s)
Alguns dos tratamentos convencionais utilizados em determinadas doenƧas, como as doenƧas oncolĆ³gicas, doenƧas inflamatĆ³ria/autoimunes, doenƧas infeciosas, e doenƧas cardiovasculares, vĆŖm apresentando diversas limitaƧƵes, seja pela libertaĆ§Ć£o imediata do fĆ”rmaco na circulaĆ§Ć£o sanguĆnea, pela falta de especificidade aos recetores de superfĆcie celular, ou pela presenƧa de efeitos colaterais.
A presente dissertaĆ§Ć£o tem como objetivo apresentar as diferentes estratĆ©gias de direcionamento/vetorizaĆ§Ć£o que podem acompanhar os diferentes nanossistemas como veiculadores de fĆ”rmacos, com o intuito de ultrapassar as limitaƧƵes das formas farmacĆŖuticas ditas convencionais. Os nanossistemas apresentam a capacidade de veicular os fĆ”rmacos para o local alvo (e.g., microambiente tumoral), permitindo proteĆ§Ć£o adicional do fĆ”rmaco com o ambiente biolĆ³gico e uma libertaĆ§Ć£o controlada. Quando se pretende aumentar a quantidade de fĆ”rmaco que atingiu o local alvo, recorre-se a uma estratĆ©gia de direcionamento ativo, como por exemplo, a funcionalizaĆ§Ć£o com anticorpos monoclonais (mAbs) Ć superfĆcie do nanossistema. Os mAbs consistem numa alternativa de ligandos de direcionamento ativo devido Ć sua capacidade de reconhecer e interagir seletivamente com os recetores de superfĆcie sobreexpressos diferencialmente em determinados Ć³rgĆ£os, tecidos, cĆ©lulas ou organelos celulares. No entanto, os mAbs tĆŖm algumas limitaƧƵes, devido Ć s suas caracterĆsticas estruturais, tais como, o diĆ¢metro elevado.
Estas estratĆ©gias tĆŖm contribuĆdo, quer seja para obter um tratamento mais direcionado, como no caso do cancro, quer seja para diagnĆ³stico e teranĆ³stico, devido Ć s propriedades fototĆ©rmicas inerentes a alguns nanossistemas que permitem a sua utilizaĆ§Ć£o como agentes de imagem. Novos estudos tĆŖm vindo a ser efetuados nesta Ć”rea, razĆ£o pela qual Ć© de esperar o desenvolvimento de novas estratĆ©gias de direcionamento para os nanossistemas, como a substituiĆ§Ć£o dos mAbs por fragmentos de anticorpos.
Some of the conventional treatments used in certain diseases, such as oncological diseases, inflammatory/autoimmune diseases, infectious diseases, and cardiovascular diseases, have presented several limitations, either by the immediate release of the drug into the bloodstream, by the lack of specificity to cell surface receptors, or the presence of side effects. The present dissertation aims to present the different targeting/vectoring strategies that can accompany the various nanosystems as drug carriers, in order to overcome the limitations of the so-called conventional pharmaceutical forms. Nanosystems have the ability to deliver drugs to the target site (e.g., tumor microenvironment), allowing additional protection of the drug from the biological environment and controlled release. When it is intended to increase the amount of drug that has reached the target site, an active targeting strategy is used, such as the functionalization with monoclonal antibodies (mAbs) on the surface of the nanosystem. mAbs are an alternative of active targeting ligands due to their ability to recognize and selectively interact with surface receptors differentially overexpressed in certain organs, tissues, cells or cellular organelles. However, mAbs have some limitations due to their structural characteristics, such as their large diameter. These strategies have contributed, whether to obtain a more targeted treatment, as in the case of cancer, or for diagnosis and theranostics, due to the photothermal properties inherent to some nanosystems that allow their use as imaging agents. New studies have been carried out in this area, which is why it is expected the development of new targeting strategies for nanosystems, such as the replacement of mAbs by antibody fragments.
Some of the conventional treatments used in certain diseases, such as oncological diseases, inflammatory/autoimmune diseases, infectious diseases, and cardiovascular diseases, have presented several limitations, either by the immediate release of the drug into the bloodstream, by the lack of specificity to cell surface receptors, or the presence of side effects. The present dissertation aims to present the different targeting/vectoring strategies that can accompany the various nanosystems as drug carriers, in order to overcome the limitations of the so-called conventional pharmaceutical forms. Nanosystems have the ability to deliver drugs to the target site (e.g., tumor microenvironment), allowing additional protection of the drug from the biological environment and controlled release. When it is intended to increase the amount of drug that has reached the target site, an active targeting strategy is used, such as the functionalization with monoclonal antibodies (mAbs) on the surface of the nanosystem. mAbs are an alternative of active targeting ligands due to their ability to recognize and selectively interact with surface receptors differentially overexpressed in certain organs, tissues, cells or cellular organelles. However, mAbs have some limitations due to their structural characteristics, such as their large diameter. These strategies have contributed, whether to obtain a more targeted treatment, as in the case of cancer, or for diagnosis and theranostics, due to the photothermal properties inherent to some nanosystems that allow their use as imaging agents. New studies have been carried out in this area, which is why it is expected the development of new targeting strategies for nanosystems, such as the replacement of mAbs by antibody fragments.
Description
Keywords
Nanossistemas Anticorpos monoclonais Direcionamento ativo Nanosystems Monoclonal antibodies Active targeting