Unraveling the role of Intralipid in suppressing off-target delivery and augmenting the therapeutic effects of anticancer nanomedicines

0542070 - ÚMCH 2022 RIV GB eng J - Článek v odborném periodiku
Islam, R. - Gao, S. - Islam, W. - Šubr, Vladimír - Zhou, J.-R. - Yokomizo, K. - Etrych, Tomáš - Maeda, H. - Fang, J.
Unraveling the role of Intralipid in suppressing off-target delivery and augmenting the therapeutic effects of anticancer nanomedicines.
Acta Biomaterialia. Roč. 126, May (2021), s. 372-383. ISSN 1742-7061. E-ISSN 1878-7568
Grant CEP: GA ČR(CZ) GA19-01417S
Grant ostatní: AV ČR(CZ) JSPS-16-05
Program: Bilaterální spolupráce
Institucionální podpora: RVO:61389013
Klíčová slova: EPR effect * off-target delivery * Intralipid
Obor OECD: Polymer science
Impakt faktor: 10.633, rok: 2021
Způsob publikování: Omezený přístup
https://www.sciencedirect.com/science/article/pii/S174270612100194X?via%3Dihub

Intralipid, a clinically used lipid emulsion, was reportedly utilized as one strategy to suppress off-target delivery of anticancer nanomedicines. Intralipid also effectively improved drug delivery to tumors and produced better therapeutic effects. However, the mechanisms involved—the why and how—in Intralipid's facilitation of delivery of nanomedicines to tumors have not yet been reported in detail. In this study, we investigated Intralipid and discovered the beneficial effects of Intralipid pretreatment when using three anticancer nanomedicines, including the clinically approved drug doxorubicin (Doxil). Intralipid pretreatment induced a 40% reduction in liver uptake of a polymeric nanoprobe used in photodynamic therapy as well as a 1.5-fold-increased nanomedicine accumulation in tumors. This increased accumulation consequently led to significantly better therapeutic effects, and this finding was validated by using Doxil. As an interesting result, Intralipid pretreatment significantly prolonged the plasma half-life of nanomedicines in normal healthy mice but not in tumor-bearing mice, which suggests that tumors become an alternative route of nanomedicine delivery when liver delivery is suppressed. Also, we found markedly increased tumor blood flow, as measured by fluorescence angiography, and significantly lower blood viscosity after Intralipid pretreatment. All our results together indicate that Intralipid treatment not only suppressed off-target nanomedicine delivery by the reticuloendothelial system, but more important, it enhanced nanomedicine delivery to tumors by improving tumor blood flow, which is key to satisfactory drug delivery via the enhanced permeability and retention effect. Significantly better therapeutic outcomes were thus achieved by the strategy of combining utilization of nanomedicines and Intralipid pretreatment.
Trvalý link: http://hdl.handle.net/11104/0319709