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Abstract Title:

Solubilization and delivery of Ursolic-acid for modulating tumor microenvironment and regulatory T cell activities in cancer immunotherapy.

Abstract Source:

J Control Release. 2020 Jan 8 ;320:168-178. Epub 2020 Jan 8. PMID: 31926193

Abstract Author(s):

Ning Zhang, Shounan Liu, Sanyuan Shi, Yuetan Chen, Fengwei Xu, Xiaohui Wei, Yuhong Xu

Article Affiliation:

Ning Zhang

Abstract:

Ursolic acid (UA) is a potent triterpenoid compound found in plants and fruits with activities modulating key cell signaling pathways involving STATs, NF-κB, and TRAIL. But it's highly hydrophobic and very poorly soluble in nature. It had been prepared as nanocrystals, solid dispersion and loaded in nanoparticles but the achieved systemic exposure and circulation half-life were not ideal. We reported the development of UA-liposomes made by HPβCD assisted active loading. Compared to lipid suspensions of UA (Lipid-UA) with similar lipid composition, the novel process enabled the formation of UA-Ca crystalline structures inside the liposomes and therefore sustained release of UA in vivo. While the UA-liposomes were not generally toxic towards 4T1 triple negative breast cancer cells, they could effectively modulate CD4CD25Foxp3T cells from 4T1 tumor bearing mouse by inhibiting STAT5 phosphorylation and IL-10 secretion. In vivo administration of UA-liposomes at 10 mg/kg dose led to reduced numbers of myeloid derived suppressor cells (MDSCs) and regulatory T cells (Tregs) residing in tumor tissues. These changes signified the correction of the tumor mediated immune-suppressive microenvironment. The UA-liposomes treatment alone was already effective in deterring tumor growth. Such a formulation may be highly promising as an immunotherapy agent and be combined with chemotherapeutics or targeted drugs.

Study Type : Animal Study

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