Abstract:
ObjectiveTo design and synthesize a novel permeable hydrogel loaded with a radiation agent for the implantation radiotherapy of tumors.
MethodsThe polymer PECT-RGDPECT:poly(ε-caprolactone-co-1, 4, 8-trioxa4.6spiro-9-undecanone)-poly(ethylene glycol)-poly(ε-caprolactone-co-1, 4, 8-trioxa4.6spiro-9-undecanone); RGD:Arg-Gly-Asp was synthesized by esterification reaction, and an 131I-labeled hyaluronic acid was prepared by amidation reaction and chloramine-T method. The chemical structure of them was characterized by 1H-NMR, and the 131I-labeled hyaluronic acid was isolated and purified by precipitation and centrifugation. Hydrogel formation was verified by vial flipping experiment, and the cytotoxicity of the polymer materials was evaluated by MTT assay. The in vivo stability and degradation of the injected hydrogel were studied using a radioactive small animal live imaging system. The in vivo antitumor effect of the 131I@PECT-RGD hydrogel was investigated by inhibiting tumor growth volume and tumor tissue section.
ResultsThe polymer PECT-RGD was non-cytotoxic and could form a stable hydrogel under the normal physiological temperature(37℃). This hydrogel is capable of self-degradation in vivo. Compared with the PBS group, the 131I@PECT-RGD hydrogel and the 131I@PECT gel showed significantly higher anti-tumor efficiency (P < 0.05, F=71.968). A significant difference in anti-tumor efficiency was found between the 131I@PECT and 131I@PECT-RGD hydrogels (P < 0.05, t=7.276). No significant difference in body weight was found among the three groups (P > 0.05, F=3.878). HE staining showed that only a small part of the tumor tissue was necrotic in the PBS group, whereas a large part of the tumor tissue was necrotic in the 131I@PECT group; the tumor tissue of the 131I@PECT-RGD group was generally necrotic.
ConclusionsThe 131I@PECT-RGD hydrogel could be injected into tumor tissue in situ and display great biocompatibility, self-degradation ability, and anti-tumor activity. Thus, this hydrogel has potential applications in local radiotherapy.