Non-thermal Acoustic Enhancement of Chemotherapeutic Effects of Cisplatin on Xenografted Cervical Cancer in Mice

Abstract

Background/aim: We examined the effect of low-intensity focused ultrasound (FUS) on unbinding cisplatin from plasma proteins and enhancing its chemotherapeutic efficacy using a mouse model of xenograft human cervical cancer.

Materials and methods: FUS, operating in a pulsed mode, was applied to a dialysis cassette immersed in a normal saline bath containing both bovine serum albumin (BSA) and cisplatin, and the unbound level of cisplatin diffused into the cassette was measured. To assess the in vivo efficacy of the technique, athymic nu/nu mice were inoculated with human cervical cancer cells under four different combinatory conditions, with and without the administration of cisplatin and FUS. FUS was delivered to the tumor mass for 1 h across four separate sessions spanning a period of 10 days, following the intraperitoneal injection of cisplatin.

Results: In vitro equilibrium dialysis revealed that non-thermal application of FUS increased the concentration of unbound cisplatin compared to cassettes that were not exposed to sonication, suggesting successful unbinding. Assessment of tumor growth in vivo showed that FUS following cisplatin administration resulted in a significant reduction in tumor growth, whereas the administration of cisplatin alone exhibited plateau growth. Without administration of cisplatin, equivalent rates of aggressive tumor growth were observed regardless of the application of FUS.

Conclusion: Pulsed application of FUS can unbind cisplatin from albumin and enhance its tumoricidal effects in cervical cancer. Further assessment of intratumoral/systemic cisplatin concentration is required to quantify its selective delivery to the tumor.

Keywords: Low intensity pulsed ultrasound; chemotherapy; cisplatin; therapeutic ultrasound; uterine cervical neoplasms.