Estudo in vitro dobortezomib conjugado com nanopartículas de ouro em células tumorais pancreáticas e em células tumorais do pulmão

As nanopartículas de ouro têm sido alvo de bastante investigação, tornando-se um vector bastante promissor para o diagnóstico e tratamento do cancro. O presente estudo revela o efeito do bortezomib (BTZ), um inibidor de proteassomas, conjugado com nanopartículas de ouro (PEGAuNPs) em células tumorais pancreáticas e células tumorais do pulmão. Os resultados mostram um notável aumento do efeito do BTZ na inibição de crescimento das células tumorais humanas (S2-013 e A549) quando conjugado com as PEGAuNPs. Por outro lado, ocorre a diminuição de toxicidade deste nanosistema nas células normais humanas (TERT-HPNE).

Autores e Afiliações:

Sílvia Castro Coelho ^a, Gabriela M. Almeida ^b,c, Filipe Santos-Silva ^b,d,e,f, Maria Carmo Pereira ^a and Manuel A. N. Coelho ^a

^a LEPABE, Department of Chemical Engineering, Faculty of Engineering, University of Porto, Porto, Portugal;

^b Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal;

^c Expression Regulation in Cancer Group, IPATIMUP, Porto, Portugal;

^d Public Awareness of Cancer Unit, IPATIMUP, Porto, Portugal;

^e Faculty of Medicine, University of Porto, Porto, Portugal;

^f Department of Biochemistry and Molecular Biology, Eppley Institute, University of Nebraska Medical Center, Omaha, NE, USA.

Abstract:

Objectives: Gold nanoparticles have become promising vectors for cancer diagnosis and treatment. The present study investigates the effect of bortezomib (BTZ), a proteasome inhibitor, conjugated with pegylated gold nanoparticles (PEGAuNPs) in pancreatic and lung cancer cells.
Methods: Synthesized gold nanoparticles (PEGAuNPs) were conjugated with bortezomib antitumor drug. We investigated the cytotoxicity induced by BTZ conjugated with functionalized gold nanopar- ticles in vitro, in the human pancreatic (S2-013) and lung (A549) cancer cell lines.

Results: We found an efficient of conjugation of BTZ with PEGAuNPs. In vitro assays showed that after 72 h’ incubation with PEGAuNPs-BTZ cancer cells revealed alterations in morphology; also for S2-013 and A549 cancer cells, the IC50 value of free BTZ is respectively 1.5 and 4.3 times higher than the IC50 value of PEGAuNPs-BTZ. Furthermore, for TERT-HPNE, the IC50 value is around 63 times lower for free BTZ than the conjugated nanovehicle. Cell growth inhibition results showed a remarkable enhancement in the effect of BTZ when conjugated with AuNPs.

Conclusions: Our findings showed that conjugation with PEGAuNPs enhance the BTZ growth-inhibition effect on human cancer cells (S2-013 and A549) and decreases its toxicity against normal cells (TERT- HPNE).

Revista: Expert Opinion on Drug Delivery


Link: http://www.tandfonline.com/doi/full/10.1080/17425247.2016.1178234