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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

  • Czech description

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • 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