Gold nanoparticle delivery-enhanced proteasome inhibitor effect in adenocarcinoma cells.
BACKGROUND
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.


OBJECTIVE
In this study, the enhancement of bortezomib activity was evaluated using gold nanoparticles coated with poly(ethylene glycol). The uptake mechanism of the gold nanoparticles in pancreatic cell lines, S2-013 and hTERT-HPNE, was assessed by laser scanning confocal microscopy (LSCM).


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 an increased toxicity on the cells when compared to the drug alone.


CONCLUSIONS
Gold nanoparticles can be used as effective delivery systems to increasing the permeation and retention of drugs in cancer cells.
University of Porto, Faculty of Engineering, Department of Chemical Engineering, LEPAE , Rua Roberto Frias, PT-4200-465 Porto , Portugal +351 225081679 ; +351 225081449 ; mcoelho@fe.up.pt.
Sílvia Castro
SC
Coelho
Sandra
S
Rocha
Petras
P
Juzenas
Paula
P
Sampaio
Gabriela M
GM
Almeida
Filipe Santos
FS
Silva
Maria Carmo
MC
Pereira
Manuel A N
MA
Coelho
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000970:Antineoplastic Agents / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects; D001897:Boronic Acids / Q000008:administration & dosage*; D000069286:Bortezomib; D016503:Drug Delivery Systems; D004357:Drug Synergism; D004847:Epithelial Cells / Q000187:drug effects; D006046:Gold / Q000737:chemistry*; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry*; D010183:Pancreatic Ducts / Q000166:cytology; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011092:Polyethylene Glycols / Q000737:chemistry; D061988:Proteasome Inhibitors / Q000008:administration & dosage*; D011719:Pyrazines / Q000008:administration & dosage*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D001897:Boronic Acids; D061988:Proteasome Inhibitors; D011719:Pyrazines; D011092:Polyethylene Glycols; D000069286:Bortezomib; D006046:Gold