Longitudinal assessment of ultrasound-guided complementary microRNA therapy of hepatocellular carcinoma

Journal of Controlled Release : Official Journal of the Controlled Release Society
Sayan Mullick ChowdhuryJuergen Karl Willmann

Abstract

Hepatocellular carcinoma (HCC) is the second-leading cause of cancer related deaths worldwide and new strategies to efficiently treat HCC are critically needed. The aim of this study was to assess the longitudinal treatment effects of two complementary miRNAs (miRNA-122 and antimiR-21) encapsulated in biodegradable poly lactic-co-glycolic acid (PLGA) - poly ethylene glycol (PEG) nanoparticles (PLGA-PEG-NPs), administered by an ultrasound-guided and microbubble-mediated delivery approach in doxorubicin-resistant and non-resistant human HCC xenografts. Using in vitro assays, we show that repeated miRNA treatments resulted in gradual reduction of HCC cell proliferation and reversal of doxorubicin resistance. Optimized US parameters resulted in a 9-16 fold increase (p = 0.03) in miRNA delivery in vivo in HCC tumors after two US treatments compared to tumors without US treatment. Furthermore, when combined with doxorubicin (10 mg/kg), longitudinal miRNA delivery showed a significant inhibition of tumor growth in both resistant and non-resistant tumors compared to non-treated, and doxorubicin treated controls. We also found that ultrasound-guided miRNA therapy was not only effective in inhibiting HCC tumor growth but also allowed low...Continue Reading

Citations

Jan 29, 2019·Frontiers in Pharmacology·Qiang LuFenghua Zhou
Dec 10, 2020·Expert Opinion on Drug Delivery·Vikas KumarHyung Sik Kim
Feb 1, 2020·Journal of Controlled Release : Official Journal of the Controlled Release Society·Jennifer C WischhusenRamasamy Paulmurugan
May 26, 2021·Biomaterials Science·Mohammed Mehadi Hassan ChowdhuryMd Nurunnabi
Oct 17, 2020·ACS Pharmacology & Translational Science·Yi LiuRamasamy Paulmurugan

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