Harnessing hyaluronic acid-based nanoparticles for combination therapy: A novel approach for suppressing systemic inflammation and to promote antitumor macrophage polarization

Vigneshkumar Rangasami, Sumanta Samanta, Vijay Parihar, Kenta Asawa, Keying Shu, Oommen P. Varghese, Yuji Teramura, Bo Nilsson, Jöns Hilborn, Robert A. Harris, Oommen P. Oommen

    Research output: Contribution to journalArticleScientificpeer-review

    4 Citations (Scopus)

    Abstract

    Anti-inflammatory drugs such as dexamethasone (DEX) are commonly administered to cancer patients along with anticancer drugs, however, the effect of DEX on human cancers is poorly understood. In this article, we have tailored self-assembled nanoparticles derived from hyaluronic acid (HA) wherein, anti-inflammatory DEX was used as a hydrophobic moiety for inducing amphiphilicity. The HA-DEX micelles were subsequently loaded with chemotherapeutic agent, doxorubicin (DOX) (HA-DEX-DOX) and was utilized to deliver drug cargo to human cancer cells expressing different levels of CD44 receptors. We found that DEX suppressed the cytotoxicity of DOX in HCT116, while it synergistically enhanced cytotoxicity in MCF-7 cells. When we tested DOX and HA-DEX-DOX in an ex-vivo human whole blood, we found activation of complement and the coagulation cascade in one group of donors. Encapsulation of DOX within the nanoparticle core eliminated such deleterious side-effects. The HA-DEX-DOX also polarized bone-marrow-derived anti-inflammatory M2 macrophages, to pro-inflammatory M1 phenotype with the upregulation of the cytokines TNF-α, iNOS and IL-1β.
    Original languageEnglish
    Article number117291
    JournalCarbohydrate Polymers
    Volume254
    DOIs
    Publication statusPublished - 27 Oct 2020
    Publication typeA1 Journal article-refereed

    Publication forum classification

    • Publication forum level 1

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