Modular Peptide Probe for Pre/Intra/Postoperative Therapeutic to Reduce Recurrence in Ovarian Cancer.

Abstract

Even with optimal surgery, 80% of patients with ovarian cancer will have recurrence. Adjuvant therapy can reduce the recurrence of tumors; however, the therapeutic effect is still not prominent. Herein, we designed a modular peptide probe (TCDTMP), which can be self-assembled into nanoparticles (NPs) by loading in miR-145-5p or VEGF-siRNA. In vivo, (1) preoperative administration of TCDTMP/miR-145-5p ensured that NPs were adequately accumulated in tumors through active targeting and increased the expression of miR-145-5p in tumors, thereby inducing tumor cell apoptosis. (2) Intraoperatively, most of the tumors were removed, while the microscopic residual tumors were largely eliminated by TCDTMP/miR-145-5p-mediated photodynamic therapy (PDT). (3) Postoperatively, TCDTMP/VEGF-siRNA were given for antiangiogenesis therapy, thus delaying the recurrence of tumors. This treatment was named a preoperative (TCDTMP/miR-145-5p)||intraoperative (surgery and PDT)||postoperative (TCDTMP/VEGF-siRNA) therapeutic system and abbreviated as the PIP therapeutic system, which reduced the recurrence of ovarian cancer in subcutaneous tumor models, intraperitoneal metastasis models, and patient-derived tumor xenograft models. Our findings provide a therapeutic system based on modular peptide probes to reduce the recurrence of ovarian cancer after surgery, which provides a perspective for the surgical management of ovarian cancer.