Panoply™ Human GNRHR Over-expressing Stable Cell Line

Cancer is a leading cause of death worldwide, particularly reproductive-related cancers (such as breast/cervical cancer in women and prostate cancer in men). Chemotherapy is the most common systemic cancer therapy, but its side effects are concerning. Developing effective novel anticancer strategies is crucial to improving efficacy and minimizing side effects. Here, researchers used high-throughput microfluidics to fabricate novel core-shell lipid nanoparticles (LNPs) for chemotherapy drug delivery. Gonadotropin-releasing hormone (GnRH), a molecule that targets the gonadotropin-releasing hormone receptor (GnRHR) overexpressed in cancer cells, was conjugated to chitosan (GnRH-CS) as a shell and used to modify the LNP surface for doxorubicin loading, forming an LNP-dox-GnRH complex. The modified surface enhanced the binding affinity of the LNP for breast and prostate cancer cells. In in vitro studies, the researchers demonstrated that LNP-dox-GnRH specifically targeted GnRHR-overexpressing cancer cells (such as MCF-7 and PC-3 cells) compared to non-targeted LNP-dox. In contrast, there was no difference in targeting between LNP-dox-GnRHR and non-targeted LNPs to the GnRHR-low-expressing cancer cell MDA-MB-436. Furthermore, enhanced anticancer activity of LNP-dox-GnRH was observed in both monolayer and spheroid cell cultures.

LNP-dox-GnRH and doxorubicin (free drug) exhibited anticancer activity against the proliferation of GnRHR-overexpressing cancer cells, including hormone-dependent MCF-7 and PC-3 cells, while MDA-MB-436 cells are hormone-independent. Using doxorubicin (free drug) as a control, the cytotoxic effect of LNP-dox-GnRH was demonstrated to be attributable to its surface targeting moiety. The results indicated that the efficacy of LNP-dox-GnRH in inducing cell death in GnRHR overexpressing MCF-7 cells and PC-3 cells was considerably superior to the cell death obtained from the free doxorubicin and LNP-dox treated groups, particularly in the case of the MCF-7 cells. In contrast, in MDA-MB-436 cells, no difference in cytotoxicity was observed between LNP-dox and LNP-dox-GnRH-treated groups, attributed to lower GnRH receptor expression (Figure 1). Based on these findings, the anticancer effect of the LNP-dox-GnRH-treated group may be enhanced compared with LNP-dox and free DOX (absorbed by passive diffusion) because LNP-dox-GnRH is more significantly internalized via receptor-mediated endocytosis.

Figure 1. Cell viability of MCF-7 (A), PC-3 (B), and MDA-MB-436 (C) after LNP-dox-GnRH, LNP-dox, and doxorubicin (free drug) treatments. (Bunwatcharaphansakun P, et al., 2025)