Nanopartículas de ouro combinadas com fármacos na terapia de tumores pancreáticos

Objetivo: A inibição de «proteasome» é um método terapêutico usado no tratamento de mieloma múltiplo. Os fármacos que controlam a atividade do “proteasome” atuam ao nível celular provocando apoptose. O Velcade (bortezomib) foi o primeiro inibidor de “proteasome” aprovado clinicamente. Esta droga é atualmente utilizada em combinação com outros agentes anti tumorais. Neste estudo, mostra-se que a atividade bortezomib pode ser melhorada através de nanopartículas de ouro revestidas com polietileno-glicol.

Métodos: O mecanismo de absorção de nanopartículas de ouro em linhas de células pancreáticas, S2-013 e hTERT-HPNE, foi observado por microscopia laser confocal de varrimento.

Resultados: As células tumorais pancreáticas internalizam as nanopartículas em conjunto com o fármaco em poucos minutos, através da formação de vesículas por endocitose. Esta rápida absorção conduz a um aumento na concentração e difusão de bortezomib no citoplasma celular, provocando um aumento significativo da toxicidade sobre as células em comparação com a quimioterapia clássica.

Conclusão: As nanopartículas de ouro podem ser utilizadas como eficazes sistemas de libertação para aumentar a penetração e retenção de drogas em células tumorais.

Autores e afiliações:

Sílvia Castro Coelho ¹, Sandra Rocha ², Petras Juzenas ³, Paula Sampaio ⁴, Gabriela M. Almeida ⁵, Filipe Santos Silva ^5,6,7, Maria Carmo Pereira ¹, Manuel A.N. Coelho ¹

^1. LEPAE, Department of Chemical Engineering, Faculty of Engineering, University of Porto, Rua Roberto Frias, PT-4200-465 Porto, Portugal
^2. Department of Chemical and Biological Engineering, Chalmers University of Technology, Gothenburg SE-41296, Sweden

^3. Department of Radiation Biology, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Montebello NO-0310 Oslo, Norway

^4. Institute for Molecular Cell Biology (IBMC), Porto, Portugal

^5. Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal

^6. Medical Faculty, University of Porto, Porto, Portugal

^7. University of Nebraska Medical Center, United States of America

 Abstract:

Objectives: Proteasome inhibition is a current therapeutic strategy used in the treatment of multiple myeloma. Drugs controlling proteasome activity are ideally suited for unidirectional manipulation of cellular pathways such as apoptosis. The first proteasome inhibitor approved in clinics was bortezomib. This drug is currently used in combination with other anticancer agents. In this study, we show that bortezomib activity can be enhanced by using gold nanoparticles coated with poly(ethylene glycol).

Methods: The uptake mechanism of the gold nanoparticles in pancreatic cell lines, S2-013 and hTERT-HPNE, was observed by laser scanning confocal microscopy. The evaluation of the cytotoxicity was performed by PrestoBlue and Sulforhodamine B assays.

Results: Pancreatic cancer cells internalized the nanoparticles together with the drug in few minutes through the formation of endocytic vesicles. This rapid uptake leads to an increase in the concentration and diffusion of bortezomib in the cytoplasm yielding to an increased toxicity on the cells when compared to the drug alone.

Conclusion: Gold nanoparticles can be used as effective delivery systems to increasing the permeation and retention of drugs in cancer cells.

Revista:

Expert Opinion on Drug Delivery

Link:

http://informahealthcare.com/doi/abs/10.1517/17425247.2013.827659