Enhancing HIPEC for Ovarian Cancer using Adjunctive Biomaterials

Area of Science:

• Gynecologic Oncology
• Biomaterials Science
• Translational Medicine

Background:

• Ovarian cancer presents a high mortality rate due to late diagnosis and peritoneal metastasis.
• Current treatments like hyperthermic intraperitoneal chemotherapy (HIPEC) face limitations including drug resistance, adhesion formation, and systemic toxicity.
• There is a critical need for innovative therapies to improve HIPEC outcomes in advanced ovarian cancer.

Purpose of the Study:

• To investigate carbon monoxide gas-entrapping materials (CO-GEMs) as a multifunctional adjunctive therapy for HIPEC.
• To evaluate CO-GEMs' ability to enhance therapeutic efficacy, prevent peritoneal adhesions, and reduce cisplatin-induced nephrotoxicity in ovarian cancer models.

Main Methods:

• Utilized CO-GEMs to deliver carbon monoxide (CO) in conjunction with HIPEC in ovarian cancer models.
• Assessed tumor burden reduction, drug resistance pathway modulation (IL-17, TNF, NF-κB, ECM, VEGF), peritoneal adhesion formation, and cisplatin-induced nephrotoxicity (blood urea nitrogen levels).

Main Results:

• CO-GEMs significantly enhanced cisplatin efficacy, reducing metastatic tumor burden by 46.6% via downregulation of key resistance pathways.
• CO-GEMs effectively prevented peritoneal adhesion formation by reducing inflammatory cell infiltration and collagen deposition.
• Enteral CO-GEMs demonstrated significant nephroprotection against cisplatin-induced acute kidney injury.

Conclusions:

• CO-GEMs represent a promising multifunctional adjunctive therapy for HIPEC in advanced ovarian cancer.
• This approach simultaneously improves treatment efficacy, mitigates surgical complications, and reduces systemic toxicity.
• CO-GEMs offer an enhanced therapeutic index and improved safety profile, potentially transforming treatment outcomes.