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Publicação
ENCAPSULAMENTO DE UM INIBIDOR DE REPARAÇÃO DE ADN EM LIPOSSOMAS PARA TRATAMENTO DO CANCRO
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Orientador(es)
Resumo(s)
Neste trabalho pretendeu-se aprimorar o conhecimento de um tratamento inovador ba-
seado na inibição de reparação do ácido desoxirribonucleico (ADN) através da utilização develiparib, uma molécula inibidora de uma proteína de reparação de ADN a
Poli (ADP-ribose)
Polimerase-1 (PARP1). Para tal, as moléculas de
veliparib foram encapsuladas em lipossomas
para que a entrega deste inibidor às células cancerígenas seja mais eficaz. Para se avaliar o
efeito do inibidor e do inibidor encapsulado foram realizados estudos de citotoxicidade e fo-
totoxicidade em duas linhagens de células. No desenvolvimento deste projeto as moléculas develiparib foram encapsuladas em lipossomas que foram preparadas a partir da mistura de 1,2-
dipalmitoil-sn-glicero fosfocolina (DPPC) com 1,2 – dipalmitoil-sn-glicero-3-fosfoglicerol
(DPPG). As soluções aquosas de
veliparib e as emulsões de
veliparib encapsulado em liposso-
mas de diferentes concentrações, foram utilizadas em ensaios in vitro de citotoxicidade da
molécula de
veliparib em células cancerígenas denominadas de carcinoma de células escamo-
sas (MET-1) e em células não cancerígenas de queratinócitos (HaCaT) e estudos de fototoxici-
dade irradiadas com UV. Estes testes permitiram analisar a viabilidade celular após a exposição
a diferentes concentrações do fármaco e o impacto da radiação UV na resposta celular. Os
resultados indicam que o
veliparib encapsulado em lipossomas é citotóxico nas células MET-1
e ao mesmo tempo reduz efeitos adversos nas células HaCaT sugerindo maior seletividade do
tratamento. Estes resultados demonstram que esta abordagem pode reduzir a toxicidade nos
tecidos saudáveis, melhorar a qualidade de vida dos pacientes e oferecer outra perspetiva de
terapia anticancerígena.
This study aims to improve knowledge of an innovative treatment based on the prevention of deoxyribonucleic acid (ADN) supplements using veliparib, an inhibitor molecule of a ADN replacement protein, Poly (ADP-ribose) Polymerase-1 (PARP1). To this end, veliparib molecules were encapsulated in liposomes so that the delivery of this inhibitor to cancer cells is more effective. To evaluate the effect of the inhibitor and the encapsulated inhibitor, cytotoxicity and phototoxicity studies were performed on two cell lines. In the development of this project, veliparib molecules were encapsulated in liposomes that were prepared from the mixture of 1,2-dipalmitoyl-sn-glycerophosphocholine (DPPC) with 1,2-dipalmitoyl-sn-glycero-3-phospho (DPPG). Aqueous solutions of veliparib and emulsions of veliparib encapsulated in liposomes of different concentrations were used in vitro cytotoxicity assays of the veliparib molecule on the indicated cancer cells of squamous cell carcinoma (MET-1) and non-cancerous keratinocyte cells (HaCaT) and phototoxicity studies irradiated with UV. These tests allowed us to analyze cell solutions after exposure to different concentrations of the drug and the impact of UV radiation on the cellular response. The results show that veliparib encapsulated in liposomes is cytotoxic in MET-1 cells and at the same time reduces the adverse effects in HaCaT cells, indicating greater treatment selectivity. These results demonstrate that this approach can reduce toxicity in healthy tissues, improve the quality of life of patients, and offer another perspective on anticancer therapy.
This study aims to improve knowledge of an innovative treatment based on the prevention of deoxyribonucleic acid (ADN) supplements using veliparib, an inhibitor molecule of a ADN replacement protein, Poly (ADP-ribose) Polymerase-1 (PARP1). To this end, veliparib molecules were encapsulated in liposomes so that the delivery of this inhibitor to cancer cells is more effective. To evaluate the effect of the inhibitor and the encapsulated inhibitor, cytotoxicity and phototoxicity studies were performed on two cell lines. In the development of this project, veliparib molecules were encapsulated in liposomes that were prepared from the mixture of 1,2-dipalmitoyl-sn-glycerophosphocholine (DPPC) with 1,2-dipalmitoyl-sn-glycero-3-phospho (DPPG). Aqueous solutions of veliparib and emulsions of veliparib encapsulated in liposomes of different concentrations were used in vitro cytotoxicity assays of the veliparib molecule on the indicated cancer cells of squamous cell carcinoma (MET-1) and non-cancerous keratinocyte cells (HaCaT) and phototoxicity studies irradiated with UV. These tests allowed us to analyze cell solutions after exposure to different concentrations of the drug and the impact of UV radiation on the cellular response. The results show that veliparib encapsulated in liposomes is cytotoxic in MET-1 cells and at the same time reduces the adverse effects in HaCaT cells, indicating greater treatment selectivity. These results demonstrate that this approach can reduce toxicity in healthy tissues, improve the quality of life of patients, and offer another perspective on anticancer therapy.
Descrição
Palavras-chave
Cancro sistema de entrega de fármaco lipossomas veliparib e inibidor PARP1