Abstract 5751: Ultrasound responsive injectable hydrogels for on-demand drug delivery

Abstract

Abstract In this work, we developed ultrasound-responsive and injectable hydrogels for local and on-demand release of chemotherapeutics to solid tumors. Injectable hydrogels were prepared by using a zwitterionic monomer, sulfobetaine methacrylate (SBMA), without using any crosslinker. Gelation was performed at -20 oC using APS/TEMED as initiator, allowing the formation of strong electrostatic interactions between poly(SBMA) chains to physically crosslink the hydrogels. Monomer and initiator concentrations were carefully optimized to achieve injectable hydrogels with mechanical and thermal stability. To render ultrasound responsivity to the hydrogels, we loaded the hydrogels with hydrophobically (dodecyl) modified mesoporous silica nanoparticles (hMSNs) with sizes around 50 nm. When insonated with low-intensity focused ultrasound (LIUS), the hMSNs incept acoustic cavitation (i.e., growth and collapse of microsized bubbles), which in turn generates mechanical effects in the hydrogels such as shock waves or water jets. We found that loading the hydrogels with hMSN did not affect their injectability, and they remained mechanically stable at 37 °C for more than a week. hMSN-loaded hydrogels demonstrated strong ultrasound responsivity even at low particle concentrations (0.1 mg/mL) and ultrasound powers (25 W, 0.02% duty cycle). Finally, we loaded the hydrogels with a chemotherapy drug, doxorubicin (DOX, 0.2 mg/mL). DOX-loaded hydrogels demonstrated minimal release without LIUS treatment (<20% in a day). Application of LIUS (150 W, 1% duty cycle) for 5 min resulted in almost complete mechanical disintegration of the hydrogels, resulting in a burst DOX release. We also showed that the amount of released DOX could be controlled by tuning the LUIS power and its duration. In summary, we developed injectable hydrogels with strong ultrasound responsivity. These hydrogels hold great promise for local and on-demand drug delivery to solid tumors, which is currently under investigation in our laboratory. Citation Format: Li Xiang, Gulsu Sener, Adem Yildirim. Ultrasound responsive injectable hydrogels for on-demand drug delivery [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5751.