3:45 PM Abstract No. 317 Thermoresponsive Nanonet as a carrier for transarterial immunomodulatory chemoembolization: an experimental study for rabbit liver cancer model

Abstract

Poly (polyethyleneglycol citrate-co-N-isopropylacrylamide) is referred to thermoresponsive nanonets that are liquid at room temperature and become a gel at physiologic temperature. Our purpose is to assess whether thermoresponsive nanonets are suitable biocarrier for transarterial Immunomodulatory chemoembolization to treat vascular malignant tumors. The Poly was mixed with Iodixanol to provide radio-opacity (poly-iodixanol). Poly(ethylene glycol)-bl-poly(propylene sulfide) (PEG-bl-PPS) nanocarriers were stably loaded with immunostimulant imiquimod (TLR7 agonist). Subsequently, doxorubicin and imiquimod-loaded nanocarriers (IM-NC) were added to the poly-iodixanol to synthesize immunomodulatory chemoembolization Nanonet (ICE-Nanonet). VX-2 tumor was directly implanted into the rabbit liver via laparotomy and was monitored with ultrasound. When the tumor reached about 2 cm, transarterial embolization was performed using; Saline only (Gr.1), Poly only (Gr.2) or ICE-Nanonet (Gr.3). Animals were euthanized at either one or 2 weeks after transarterial embolization. Histopathologic categorization was performed based on the distribution pattern of viable tumor cells and tumor necrosis: Cat A as peripheral viable tumor cells with central necrosis and Cat B as tumor necrosis seen at both central and periphery of tumor mass. Sixteen animals [Gr.1 (n = 4), Gr.2 (n = 2) and Gr.3 (n = 10)] that had successful liver tumor implantation and embolization were included. Histopathological examinations were performed in 2, 2, and 7 animals in Gr.1, Gr.2, and Gr.3, respectively. Viable tumor cells were seen in all specimens. Cat.A pattern was seen in all Gr.1 (100%, n = 2/2), 50% in Gr.2 (n = 1/2) and 14.3% in Gr.3 (n = 1/7). Cat.B pattern was seen in 85.7% in Gr.3 (n = 6/7), 50% in Gr.2 (n = 1/2) and no animal showed Cat.B pattern in Gr.1. Immunomodulatory chemoembolization using nanonet compound is feasible and appears to have preliminary efficacy over control in this pilot study. Using poly-dependent embolization for localized sustained delivery of immunomodulatory nanotherapeutics may have future potential for initiating additional tumor control in the rabbit liver cancer model.