Gold nanoparticles conjugated with cisplatin/doxorubicin/capecitabine lower the chemoresistance of hepatocellular carcinoma-derived cancer cells.
OBJECTIVE
The aim of the current study was to evaluate in vitro the anti-tumor efficacy of gold nanoparticles (GNPs) conjugated with conventional chemotherapy drugs for the treatment of liver cancer. This approach based on gold proposes a novel platform therapy with minimal toxicity and increased efficacy profiles for the destruction of hepatic cancer cells.


METHODS
GNPs, stabilized with a monolayer of L-aspartate and additional cytostatic drugs, were successfully used as a complex tumor-targeting drug-delivery system. The drugs (doxorubicin, cisplatin, and capecitabine) were non-covalently conjugated onto the hydrophilic assemblies of GNPs-L-Aspartate nanostructure. Transmission electron microscopy was used to characterize the morphological and structural properties of these drug-metallic nanostructures.


RESULTS
The cellular proliferation rates in the presence of the anti-cancer drugs delivered by the GNPs were found to be statistically lower than those of cells exposed to the cytostatic drugs alone, indicating that GNPs facilitated an increased susceptibility of cancer cells to cisplatin, doxorubicin, and capecitabine plus ribavirin.


CONCLUSIONS
This approach could offer a new chemotherapy strategy for patients diagnosed with unresectable hepatocellular carcinoma (HCC).
Department of Medicine, Division of Gastroenterology and Hepatology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. ciprian.tomuleasa@gmail.com
Ciprian
C
Tomuleasa
Olga
O
Soritau
Anamaria
A
Orza
Mircea
M
Dudea
Bobe
B
Petrushev
Ofelia
O
Mosteanu
Sergiu
S
Susman
Adrian
A
Florea
Emoke
E
Pall
Mihaela
M
Aldea
Gabriel
G
Kacso
Victor
V
Cristea
Ioana
I
Berindan-Neagoe
Alexandru
A
Irimie
D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D000069287:Capecitabine; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology / Q000648:ultrastructure; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology; D004317:Doxorubicin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology; D006046:Gold; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000648:ultrastructure; D053768:Metal Nanoparticles; D046529:Microscopy, Electron, Transmission; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D003841:Deoxycytidine; D000069287:Capecitabine; D006046:Gold; D004317:Doxorubicin; D002945:Cisplatin; D005472:Fluorouracil