CD133 Targeted PVP/PMMA Microparticle Incorporating Levamisole for the Treatment of Ovarian Cancer

Abstract

Levamisole (LEVA) is used to treat worm infections, but it can also inhibit cancer cell growth by inhibiting the aldehyde dehydrogenase pathway. Therefore, here, we developed a drug carrier targeting CD133, a biomarker overexpressed in ovarian cancer cells. The particle structure and cytotoxicity of the prepared LEVA-containing particles—called LEVA/PVP/PMMA microparticles (MPs) (because it used matrix material polyvinylpyrrolidone (PVP) and poly(methylmethacrylate) (PMMA))—were investigated in the ovarian cancer cell lines SKOV-3 and CP70. The particle size of the MPs was determined to be 1.0–1.5 µm and to be monodispersed. The hydrophilic property of PVP created a porous MP surface after the MPs were soaked in water for 20 min, which aided the leaching of the hydrophilic LEVA out of the MPs. The encapsulation efficiency of LEVA/PVP/PMMA MPs could reach up to 20%. Free-form LEVA released 50% of drugs in <1 h and 90% of drugs in 1 day, whereas the drug release rate of LEVA/PVP/PMMA MPs was much slower; 50% released in 4 h and only 70% of drugs released in 1 day. In the in vitro cell model test, 5 mM free-form LEVA and 0.1 g/mL CD133 targeted LEVA/PVP/PMMA MPs reduced SKOV-3 cell viability by 60%; 0.1 g/mL LEVA/PVP/PMMA MPs was equivalent to a similar dosage of the free drug. In addition, the cytotoxicity of CD133-conjugated LEVA/PVP/PMMA MPs shows a different cytotoxicity response toward cell lines. For SKOV-3 cells, treatment with free-form LEVA or CD133-conjugated LEVA/PVP/PMMA MPs exerted dose-dependent cytotoxic effects on SKOV-3 cell viability. However, CD133-conjugated LEVA/PVP/PMMA MPs demonstrated no significant dose-dependent cytotoxic efficacy toward CP70 cells.

The potential immunomodulatory effect of levamisole in humans and farm animals

“…Moreover, it was suggested that levamisole mimics the function of nonsteroidal anti-inflammatory drugs and inhibits endothelial cell proliferation, migration, and tube formation [80] . Wang et al [81] evaluated the effect of levamisole on an ovarian cancer cell line. They observed that levamisole exhibited a substantial effect on decreasing the rate of proliferation and growth of ovarian cancer cells in a dose-dependent manner [81] .…”

“…Wang et al [81] evaluated the effect of levamisole on an ovarian cancer cell line. They observed that levamisole exhibited a substantial effect on decreasing the rate of proliferation and growth of ovarian cancer cells in a dose-dependent manner [81] . Concomitant use of levamisole with common anticancer drugs such as chlorambucil, leucovorin, and fluorouracil has been shown to be strongly synergistic, and as a result, researchers have recommended the concomitant use of levamisole with anticancer agents [82 , 83] .…”

Significantly high expression of NUP37 leads to poor prognosis of glioma patients by promoting the proliferation of glioma cells

“…Koppany Visnyei et al confirmed that emetine inhibited the proliferation of glioma cells 39 . Levamisole minimizes drug side effects and inhibits the activity of ovarian cancer cells 40 . Riboflavin has a blue light activation effect, which produce reactive oxygen species (ROS) to inhibit the activity of cancer cells 41 .…”

“…39 Levamisole minimizes drug side effects and inhibits the activity of ovarian cancer cells. 40 Riboflavin has a blue light activation effect, which produce reactive oxygen species (ROS) to inhibit the activity of cancer cells. 41 Some drugs have new therapeutic effects that allow them play an unexpected role in the treatment of certain diseases, which accelerates the process of drug development.…”

Advances in the role of GPX3 in ovarian cancer (Review)

“…CD133 + is a glycosylated membrane protein that was initially discovered in murine neuroepithelial stem cells and is identified as a marker for CSCs in brain tumors (65). A study by Liou (65) revealed that CD133 can modulate cell cycle progression by affecting Wnt signaling and promoting the invasiveness of tumor cells (64)(65)(66)(67). CD117 is a tyrosine kinase receptor, and peritoneal fluid obtained from patients with OC having CD117 + cells can form tumors with the same self-renewal and differentiation capacity as cells derived from the tumor (68).…”