A biodegradable multifunctional porous microsphere composed of carrageenan for promoting imageable trans-arterial chemoembolization

Abstract

Trans-arterial chemoembolization (TACE) has been a mainstream treatment for hepatocellular carcinoma (HCC), accordingly there are more requirements for embolic agents’ properties, mainly concentrated on biodegradability and imaging function. A new kind of biodegradable multifunctional porous microspheres (BMPMs) with internal coarse plications are ingeniously designed and manufactured, consisting of carrageenan, inhexol and superparamagnetic iron oxide nanoparticle (SPIO). BMPMs’ sound roundness and excellent swelling behavior guarantee them to be smoothly transported into appointed arteries’ ends and achieve satisfactory embolization effect. Porous structure together with sulphate groups on BMPMs’ skeleton weaved by cross-linked carrageenan contributes to a marvelous doxorubicin hydrochloride (Dox) loading capacity over 45 mg Dox per mL of swollen microspheres, as well as a controllable degradation rate by allowing enzymes to infiltrate into BMPMs through holes, degrading 20–35% after two months in vitro. Inner coarse plications enable BMPMs to effectively combine with iohexol via hydrophilic effect and SPIO by blocking, which can further exhibit a decent imaging performance under digital subtraction system (DSA) and magnetic resonance imaging (MRI) for optimization of current TACE and development of a more advanced imageable TACE (iTACE). Safety evaluation and animal experiment manifest that BMPMs are reliable enough and hold great potential and competitiveness of being used in curing HCC.