Impacts of Intralipid on Nanodrug Abraxane Therapy and on the Innate Immune System.

Autor: Chen YJ; National Institute of Cancer Research, National Health Research Institutes, Miaoli, County, Taiwan., Tsai CY; Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli, County, Taiwan., Cheng YM; National Institute of Cancer Research, National Health Research Institutes, Miaoli, County, Taiwan., Nieh SW; National Institute of Cancer Research, National Health Research Institutes, Miaoli, County, Taiwan., Yeh TK; Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli, County, Taiwan., Chen CP; Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli, County, Taiwan., Wang MH; Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli, County, Taiwan., Chou LH; Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli, County, Taiwan., Chiu TY; Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli, County, Taiwan., Liu L; National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA., Ho C; Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA, USA. chienho@andrew.cmu.edu., Chen CT; Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli, County, Taiwan. ctchen@nhri.edu.tw., Liu TW; National Institute of Cancer Research, National Health Research Institutes, Miaoli, County, Taiwan. walter@nhri.edu.tw.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2020 Feb 18; Vol. 10 (1), pp. 2838. Date of Electronic Publication: 2020 Feb 18.
DOI: 10.1038/s41598-020-59813-7
Abstrakt: A major obstacle to nanodrugs-mediated cancer therapy is their rapid uptake by the reticuloendothelial system that decreases the systemic exposure of the nanodrugs to tumors and also increases toxicities. Intralipid has been shown to reduce nano-oxaliplatin-mediated toxicity while improving bioavailability. Here, we have found that Intralipid reduces the cytotoxicity of paclitaxel for human monocytic cells, but not for breast, lung, or pancreatic cancer cells. Intralipid also promotes the polarization of macrophages to the anti-cancer M1-like phenotype. Using a xenograft breast cancer mouse model, we have found that Intralipid pre-treatment significantly increases the amount of paclitaxel reaching the tumor and promotes tumor apoptosis. The combination of Intralipid with half the standard clinical dose of Abraxane reduces the tumor growth rate as effectively as the standard clinical dose. Our findings suggest that pre-treatment of Intralipid has the potential to be a powerful agent to enhance the tumor cytotoxic effects of Abraxane and to reduce its off-target toxicities.
Databáze: MEDLINE
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