Octreotide modified liposomes that co-deliver paclitaxel and neferine effectively inhibit ovarian cancer metastasis by specifically binding to the SSTR2 receptors

Early detection of ovarian cancer is challenging, leading to high mortality rates. Paclitaxel has broad-spectrum anti-tumor activity and has been used clinically for the treatment of various cancers. However, the severe side effects of paclitaxel limit its use at high doses. Hence, it is imperative to develop a novel anti-neoplastic agent that can enhance therapeutic efficacy and selectively target tumor sites, thereby mitigating systemic toxicity. In this study, lipid nanoparticles with surface-modified octreotide were constructed by a thin film dispersion method to co-encapsulate paclitaxel and neferine, which are lipophilic compounds, within the phospholipid bilayer, improving their solubility. Liposomes modified with octreotide can increase its active targeting to SKOV3 cells through SSTR-mediated endocytosis and prolong the drug circulation time in vivo. The potential synergistic effects of paclitaxel and neferine were confirmed and quantified by Synergyfinder analysis software. In vitro experimental results showed that neferine can synergistically enhance the cytotoxicity of paclitaxel against human ovarian cancer cells, exerting anti-proliferative, apoptosis-inducing, invasion-suppressing, and angiogenesis-disrupting effects. The in vivo targeting and tumor inhibition of Octreotide-modified liposomes that co-deliver paclitaxel and neferine (OCT-PTX/Nef-Lips) were investigated in mice xenografted with SKOV3 cells. In vivo pharmacodynamic evaluation demonstrated the safe and effective ability of OCT-PTX/Nef-Lips to inhibit tumor volume growth, disrupt tumor tissue morphology, induce apoptosis in tumor cells, and suppress their proliferation. Furthermore, angiogenesis was inhibited through down-regulation of angiogenesis-related proteins (TIE-2, VEGFA, VE-Cadherin, Ang-2).