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Published on: March 25, 2019
Modular Peptide Probe for Pre/Intra/Postoperative Therapeutic to Reduce Recurrence in Ovarian Cancer
Jun Dai1, Yong Cheng2, Jun Wu2
1Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430032, China.
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.
Insights
A novel modular peptide probe system (PIP) effectively reduces ovarian cancer recurrence by combining preoperative, intraoperative, and postoperative therapies. This innovative approach targets tumor cells and inhibits angiogenesis, offering a new strategy for surgical management.
Area of Science:
- Biomedical Engineering
- Oncology
- Nanotechnology
Background:
- Ovarian cancer recurrence remains high (80%) despite optimal surgery.
- Current adjuvant therapies show limited efficacy in preventing tumor recurrence.
Purpose of the Study:
- To develop a modular peptide probe-based therapeutic system (PIP) to reduce ovarian cancer recurrence.
- To investigate the efficacy of a multi-stage therapeutic strategy involving preoperative, intraoperative, and postoperative interventions.
Main Methods:
- Design of a modular peptide probe (TCDTMP) capable of self-assembling into nanoparticles (NPs).
- Loading NPs with miR-145-5p for preoperative apoptosis induction and VEGF-siRNA for postoperative anti-angiogenesis.
- Integration of TCDTMP/miR-145-5p with photodynamic therapy (PDT) for intraoperative residual tumor elimination.
Main Results:
- Preoperative TCDTMP/miR-145-5p actively targeted tumors, induced apoptosis, and increased miR-145-5p expression.
- Intraoperative PDT effectively eliminated microscopic residual tumors post-surgery.
- Postoperative TCDTMP/VEGF-siRNA suppressed tumor recurrence through anti-angiogenesis.
Conclusions:
- The PIP therapeutic system significantly reduced ovarian cancer recurrence in various preclinical models.
- This modular peptide probe-based system offers a promising perspective for improving ovarian cancer surgical management.
