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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389013%3A_____%2F21%3A00542070" target="_blank" >RIV/61389013:_____/21:00542070 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S174270612100194X?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S174270612100194X?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.actbio.2021.03.044" target="_blank" >10.1016/j.actbio.2021.03.044</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10404 - Polymer science

Projekt

<a href="/cs/project/GA19-01417S" target="_blank" >GA19-01417S: V nádoru aktivovatelná nanoléčiva jako vícestupňové systémy pro dopravu léčiv a experimentální léčbu hematologických malignit</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2021

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Acta Biomaterialia

ISSN

1742-7061

e-ISSN

1878-7568

Svazek periodika

126

Číslo periodika v rámci svazku

May

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

12

Strana od-do

372-383

Kód UT WoS článku

000646004400007

EID výsledku v databázi Scopus

2-s2.0-85103718542