TY - JOUR
T1 - Multiple layer-by-layer lipid-polymer hybrid nanoparticles for improved folfirinox chemotherapy in pancreatic tumor models
AU - Li, Feng
AU - Zhao, Xiao
AU - Wang, Hai
AU - Zhao, Ruifang
AU - Ji, Tianjiao
AU - Ren, He
AU - Anderson, Gregory J.
AU - Nie, Guangjun
AU - Hao, Jihui
N1 - Publisher Copyright:
© 2014 WILEY-VCH Verlag GmbH & Co. KGaA , Weinheim.
PY - 2015/2/4
Y1 - 2015/2/4
N2 - The FOLFIRINOX regimen, a combination of three chemotherapy agents (5-fl uorouracil, irinotecan, oxaliplatin) and folinic acid (a vitamin B derivatives reducing the side effect of 5-fl uorouracil), has proved to be effective in the treatment of pancreatic cancer, and is more effi cacious than the long-term reference standard, gemcitabine. However, the FOLFIRINOX is associated with high-grade toxicity, which markedly limits its clinical application. Encapsulation of drugs in nanocarriers that selectively target cancer cells promises to be an effective method for co-delivery of drug combinations and to mitigate the side effects of conventional chemotherapy. Here we reported the development of multiple layer-by-layer lipid-polymer hybrid nanoparticles with targeting capability that show excellent biocompatibility and synergistically combine the favorable properties of liposomes and polymer nanoparticles. Relative to nanoparticles consisting of polymer alone, these novel nanocarriers have a long half-life in vivo and a higher stability in serum. The nanocarriers were loaded with the three active antitumor constituents of FOLFIRINOX regimen. Little drugs were released from the nanoparticles in phosphate buffered saline (PBS) solution, but the cargoes were quickly released after the nanoparticles were taken up by tumor cells. These innovative drug-loaded nanoparticles achieved higher antitumor effi cacy and showed minimal side effects compared with the FOLFIRINOX regimen alone. Our study suggested that the multiple layer-by-layer hybrid nanoparticles have great potential for improving the chemotherapeutic effi cacy for the patients with pancreatic cancer. This platform also provides new opportunities for tailored design of nanoparticles that may offer therapeutics benefi ts for a range of other tumors.
AB - The FOLFIRINOX regimen, a combination of three chemotherapy agents (5-fl uorouracil, irinotecan, oxaliplatin) and folinic acid (a vitamin B derivatives reducing the side effect of 5-fl uorouracil), has proved to be effective in the treatment of pancreatic cancer, and is more effi cacious than the long-term reference standard, gemcitabine. However, the FOLFIRINOX is associated with high-grade toxicity, which markedly limits its clinical application. Encapsulation of drugs in nanocarriers that selectively target cancer cells promises to be an effective method for co-delivery of drug combinations and to mitigate the side effects of conventional chemotherapy. Here we reported the development of multiple layer-by-layer lipid-polymer hybrid nanoparticles with targeting capability that show excellent biocompatibility and synergistically combine the favorable properties of liposomes and polymer nanoparticles. Relative to nanoparticles consisting of polymer alone, these novel nanocarriers have a long half-life in vivo and a higher stability in serum. The nanocarriers were loaded with the three active antitumor constituents of FOLFIRINOX regimen. Little drugs were released from the nanoparticles in phosphate buffered saline (PBS) solution, but the cargoes were quickly released after the nanoparticles were taken up by tumor cells. These innovative drug-loaded nanoparticles achieved higher antitumor effi cacy and showed minimal side effects compared with the FOLFIRINOX regimen alone. Our study suggested that the multiple layer-by-layer hybrid nanoparticles have great potential for improving the chemotherapeutic effi cacy for the patients with pancreatic cancer. This platform also provides new opportunities for tailored design of nanoparticles that may offer therapeutics benefi ts for a range of other tumors.
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U2 - 10.1002/adfm.201401583
DO - 10.1002/adfm.201401583
M3 - Article
AN - SCOPUS:85028172309
SN - 1616-301X
VL - 25
SP - 788
EP - 798
JO - Advanced Functional Materials
JF - Advanced Functional Materials
IS - 5
ER -