ABSTRACT
Nanoparticles offer many promising advantages for improving current surgical regimens through their ability to detect and treat disseminated colorectal cancer (CRC). Hybrid Donor-Acceptor Polymer Particles (HDAPPs) have recently been shown to fluorescently detect and thermally ablate tumors in a murine model. Here, HDAPPS were functionalized with hyaluronic acid (HA) to improve their binding specificity to CT26 mouse CRC cells using HA to target the cancer stem cell marker CD44. In this work, we compared the binding of HA functionalized HDAPPs (HA-HDAPPs) in in vitro, ex vivo, and in vivo environments. The HA-HDAPPs bound to CT26 cells 2-fold more in vitro and 2.3-fold higher than un-functionalized HDAPPs ex vivo. Compared to intraoperative abdominal perfusion, intraperitoneal injection prior to laser stimulation for nanoparticle heat generation provides a superior modality of HA-HDAPPs delivery for CRC tumor selectivity. Photothermal treatment of disseminated CRC showed that only HA-HDAPPs delivered via intraperitoneal injection had a reduction in the tumor burden, and these nanoparticles also remained in the abdomen following resolution of the tumor. The results of this work confirm that HA-HDAPPs selectively bind to disseminated CRC, with ex vivo tumors having bound HA-HDAPPs capable of photothermal ablation. HA-HDAPPs demonstrated superior binding to tumor regions compared to HDAPPs. Overall, this study displays the theranostic potential of HDAPPs, emphasizing their capacity to detect and photothermally treat disseminated CRC tumors.
