y Role of sphingomyelin on the interaction of the anticancer drug gemcitabine hydrochloride with cell membrane models

Autor(es)

Materon, Elsa M. ^{[1, 2]} ; Nascimento, Gustavo F. ^[1] ; Shimizu, Flavio M. ^{[1, 3]} ; Camara, Amanda S. ^[1] ; Sandrino, Bianca ^[1] ; Faria, Ronaldo C. ^[2] ; Oliveira Jr, Osvaldo N.

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sao Carlos Inst Phys, POB 369, BR-13560970 Sao Carlos, SP - Brazil

^[2] Univ Fed Sao Carlos, Chem Dept, CP 676, BR-13565905 Sao Carlos, SP - Brazil

^[3] Univ Campinas UNICAMP, Gleb Wataghin Inst Phys IFGW, Dept Appl Phys, BR-13083859 Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: COLLOIDS AND SURFACES B-BIOINTERFACES; v. 196, DEC 2020.
• Citações Web of Science: 0

Resumo

The fight against drug resistance in chemotherapy requires a molecular-level understanding of the drug interaction with cell membranes, which today is feasible with membrane models. In this study, we report on the interaction of gemcitabine (GEM), a pyrimidine nucleoside antimetabolite used to treat pancreatic cancer, with Langmuir films that mimic healthy and cancerous cell membranes. The cell membrane models were made with eight compositions of a quaternary mixture containing 1,2-dipalmitoyl-sn-glycerol-3-phosphocholine (DPPC), 1,2-dipalmitoyl-sn-glycero-3-phosphoserine (DPPS), sphingomyelin (SM), and cholesterol (CHOL). The relative concentration of SM was increased so that four of these compositions represented cancerous cells. GEM was found to increase the mean molecular area, also increasing their surface elasticity, with stronger interactions being observed for membranes corresponding to cancerous cells. More specifically, GEM penetrated deepest in the membrane with the highest SM concentration (40 mol%), as inferred from polarization-modulated infrared reflection absorption spectroscopy (PM-IRRAS). This finding was confirmed with molecular dynamics simulations that also indicated how GEM approaches the membrane, which could be useful for guiding the design of drug delivery systems. The experimental and simulation results are consistent with the preferential attachment of GEM onto cancerous cells and highlight the role of SM on drug-cell interactions. (AU)

• Processo FAPESP: 12/15543-7 - Biossensores para detectar Escherichia coli usando o conceito de línguas eletrônicas
• Beneficiário: Flavio Makoto Shimizu
• Linha de fomento: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 17/24053-7 - Desenvolvimentos de métodos eletroquímicos simples para a detecção de biomarcadores visando o diagnóstico de doenças
• Beneficiário: Ronaldo Censi Faria
• Linha de fomento: Auxílio à Pesquisa - Regular
• Processo FAPESP: 17/04712-6 - Estudo das interações do fármaco cloridrato de gencitabina com modelos de membranas lipídicas
• Beneficiário: Gustavo Freitas Do Nascimento
• Linha de fomento: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 18/22214-6 - Rumo à convergência de tecnologias: de sensores e biossensores à visualização de informação e aprendizado de máquina para análise de dados em diagnóstico clínico
• Beneficiário: Osvaldo Novais de Oliveira Junior
• Linha de fomento: Auxílio à Pesquisa - Temático