Glucocorticoid Receptor-mediated Delivery of Paclitaxel and Anticancer Gene p53 for Oral Cancer Therapeutics

Abstract Metastasis in its micro and macro state contributes to the poor survival and prognosis rate in Oral Squamous Cell Carcinoma (OSCC) patients. Conventional anti-cancer treatments such as surgery, chemotherapy, and radiotherapy are known for their non-selective killing of rapidly dividing cells, both normal and cancer. To address the drawbacks arising from these modalities, we aimed to target the Glucocorticoid Receptors (GR) of OSCC to selectively co-deliver the Paclitaxel and p53 gene that induces the drug sensitivity and cytotoxicity, thereby inducing the mesenchymal-epithelial transition. To optimize the failure of data replication in in vivo, research time, and cost for cancer research, we developed an ex vivo 3D model that mimics the in vivo TME in an in vitro culture. The efficacy of these GR-mediated liposomes was therefore analyzed on different platforms: 2D monolayer, 3D spheroids, and in vivo tumor model. The parameter of spheroid diameter in the 3D model was in synchrony with the cytotoxicity data from the monolayer culture. In contrast, significant tumor regression was observed in a developed syngenic mouse model of an aggressive oral cancer. On mechanistic investigation, the upregulated E-cadherin/Vimentin ratio and downregulated VEGFR2 levels verified MET induction and angiogenesis reduction in a mouse model.