Abstract
Background: Transarterial Chemoembolization was introduced as a palliative treatment for patients with unresectable HCC. However, the drug delivery system seems to be inconsistent and unstable in maintaining a high concentration of drugs at tumor sites. This study evaluated the embolic activity and anti-tumor effects of poly (ethylene glycol) diacrylate (PEGdA) and thiolated gelatin poly (ethylene glycol) (Gel-PEG-Cys) cross-linked hydrogels loaded with cisplatin in vivo HCC models.
Methods: The delivery system is UV-sensitive hydrogels containing a chemotherapeutic drug (cisplatin). Hydrogels were made at 0.5%(w/v) photoinitiator, 10% (w/v) PEGdA, and 10% (w/v) Gel-PEG-Cys. The nude mice with orthotopic liver tumor (developed from MHCC97L cell line, located at the left lobe) were injected with hydrogels from the left branch of portal vein with the exposure of UV light. Then the development of tumor in mice were visualized using in vivo imaging system (Perkin Elmer IVIS Spectrum). The anti-tumor capacities and the associated mechanism were further explored.
Results: Severe liver damage was induced by lack of blood supply without cardiovascular nor pulmonary embolism in nude mice after hydrogel injection (Fig.A). In addition, hydrogels were found blocking in the tiny branches of portal vein around the tumor area. Cisplatin-loaded hydrogels significantly decreased the development of HCC compared to the control (Fig.B). Mice treated with cisplatin-loaded hydrogels exhibited a significant 1.8-fold decrease in signal intensity of HCC tumor compared to the control (P=0.024) after 4 weeks (Fig.C). Besides, increased inflammatory cell infiltration and tumor apoptosis and necrosis were observed in the tumor area.
Conclusions: The injectable and biodegradable hydrogels may offer the advantage of transarterial chemoembolization locally to maximize their effects on hepatocellular carcinoma.