Unraveling the role of Intralipid in suppressing off-target delivery and augmenting the therapeutic effects of anticancer nanomedicines
The result's identifiers
Result code in 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>
Result on the web
<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>
Alternative languages
Result language
angličtina
Original language name
Unraveling the role of Intralipid in suppressing off-target delivery and augmenting the therapeutic effects of anticancer nanomedicines
Original language description
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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10404 - Polymer science
Result continuities
Project
<a href="/en/project/GA19-01417S" target="_blank" >GA19-01417S: Tumor-microenvironment responsive nanomedicines as multistage drug delivery systems for experimental therapy of hematologic malignancies</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Acta Biomaterialia
ISSN
1742-7061
e-ISSN
1878-7568
Volume of the periodical
126
Issue of the periodical within the volume
May
Country of publishing house
GB - UNITED KINGDOM
Number of pages
12
Pages from-to
372-383
UT code for WoS article
000646004400007
EID of the result in the Scopus database
2-s2.0-85103718542