(PM P3) Gold Nanorod-Mediated Hyperthermia Can Improve Chemotherapeutic Efficacy in HIPEC

Introduction: Treatment of peritoneal surface malignancies with cytoreductive surgery and HIPEC has substantial risk of local recurrence and causes off-target toxicity. We sought to reinvent HIPEC utilizing a gold nanorod (GNR) platform to provide precision delivery of mild hyperthermia (42⁰C) to increase chemotherapeutic efficacy and reduce toxicity.

Methods: A biocompatible hydrogel film containing GNRs and cisplatin (CisPt) was designed to create controlled, mild hyperthermia that can be generated from NIR laser treatment of GNRs. The concentration of GNRs and duration of hyperthermia was determined using dose-response curves to titrate to goal temperature parameters. Loading and release efficiency of CisPt at an IC50 dose was quantified. SNU-16 was treated with GNR-, CisPt- or GNR+CisPt-film and NIR laser to determine cytotoxicity.

Results: Thirty seconds of NIR irradiation to film with GNR concentration of 2.35x1010 particles/ml achieved mild hyperthermia (42⁰C) in a controlled fashion. CisPt-film was loaded with 80% efficiency and released with 90% efficiency. Treatment of SNU-16 with GNR+CisPt-film and NIR laser to 42⁰C resulted in significantly increased cytotoxicity compared to CisPt-film (p<0.05).

Conclusion: NIR laser treatment of hydrogel film containing gold nanorods and chemotherapy improved the efficacy of cisplatin in gastric cancer cells. Preclinical evidence of improved efficacy utilizing a biocompatible hydrogel GNR-CisPt film could lead to clinical trials in peritoneal malignancies. If successful, treatment of other cancers could benefit from this film as a method to decrease the incidence of local recurrence in any surgical resection bed.