TY - JOUR
T1 - Bio-and hemo-compatible silk fibroin pegylated nanocarriers for 5-fluorouracil chemotherapy in colorectal cancer
T2 - In vitro studies
AU - Hudiță, Ariana
AU - Radu, Ionuț Cristian
AU - Zaharia, Cătălin
AU - Ion, Andreea Cristina
AU - Ginghină, Octav
AU - Gălățeanu, Bianca
AU - Măruțescu, Luminița
AU - Grama, Florin
AU - Tsatsakis, Aristidis
AU - Gurevich, Leonid
AU - Costache, Marieta
N1 - Funding Information:
This work was supported by a grant of Ministry of Research and Innovation, CNCS-version UEFISCDI,of theprojectmanuscript.number PN-III-P1-1.1-PD-2016-1966?MagNaNoTer, within PNCDI III. Funding: This work was supported by a grant of Ministry of Research and Innovation, CN.
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021
Y1 - 2021
N2 - 5-fluorouracil (5-FU) remains the gold standard of treatment for colorectal cancer, but its poor bioavailability and high systemic toxicity highlight the urgent need for the development of novel delivery strategies to increase the efficacy of 5-FU treatment. The present study is aimed to design and validate a PEGylated Silk Fibroin Nanocarrier (SF/PEG nanoparticles (NPs)) as an efficient 5-FU delivery system for potential intravenous administration. Using the human adenocarcinoma HT–29 cell line as an in vitro model for colorectal cancer, the cytotoxicity screening of the SF/PEG NPs showed that pristine nanocarriers were highly biocompatible, while the addition of 5-FU triggers a dramatic reduction in tumor cell viability, proliferation potential and mitochondrial integrity as well as a significant increase in nitric oxide production. Despite their high in vitro cytotoxicity, the 5-FU SF/PEG NPs were found hemocompatible as no impact on red blood cells hemolysis or the phagocytic activity of the granulocytes was observed. Exposure of HT–29 tumor cells and blood samples to 5-FU SF/PEG NPs augmented the tumor necrosis factor-α levels. Moreover, 5-FU SF/PEG NPs showed an impact on tumor cell migration and invasive potential as both of these processes were inhibited by the NP treatment.
AB - 5-fluorouracil (5-FU) remains the gold standard of treatment for colorectal cancer, but its poor bioavailability and high systemic toxicity highlight the urgent need for the development of novel delivery strategies to increase the efficacy of 5-FU treatment. The present study is aimed to design and validate a PEGylated Silk Fibroin Nanocarrier (SF/PEG nanoparticles (NPs)) as an efficient 5-FU delivery system for potential intravenous administration. Using the human adenocarcinoma HT–29 cell line as an in vitro model for colorectal cancer, the cytotoxicity screening of the SF/PEG NPs showed that pristine nanocarriers were highly biocompatible, while the addition of 5-FU triggers a dramatic reduction in tumor cell viability, proliferation potential and mitochondrial integrity as well as a significant increase in nitric oxide production. Despite their high in vitro cytotoxicity, the 5-FU SF/PEG NPs were found hemocompatible as no impact on red blood cells hemolysis or the phagocytic activity of the granulocytes was observed. Exposure of HT–29 tumor cells and blood samples to 5-FU SF/PEG NPs augmented the tumor necrosis factor-α levels. Moreover, 5-FU SF/PEG NPs showed an impact on tumor cell migration and invasive potential as both of these processes were inhibited by the NP treatment.
KW - 5FU
KW - Colorectal cancer
KW - Cytotoxicity
KW - Drugs delivery systems
KW - Inflammation
KW - Migration and invasion
KW - Polymeric nanoparticles
UR - http://www.scopus.com/inward/record.url?scp=85107007965&partnerID=8YFLogxK
U2 - 10.3390/pharmaceutics13050755
DO - 10.3390/pharmaceutics13050755
M3 - Journal article
AN - SCOPUS:85107007965
SN - 1999-4923
VL - 13
JO - Pharmaceutics
JF - Pharmaceutics
IS - 5
M1 - 755
ER -