Microalgae-based biodegradable embolic agent for the treatment of hepatocellular carcinoma through transarterial embolization

Transarterial chemoembolization (TACE) serves as a locoregional therapy for hepatocellular carcinoma (HCC) patients. Nevertheless, the rapid dissociation of conventional TACE (cTACE) preparations, attributed to the instability of the emulsion, often leads to inadequate concentrations of chemotherapeutic agents within the tumor site. Consequently, there exists a pressing demand for an embolic agent that possesses facile injectability and the capacity to provide continuous delivery of chemotherapy drugs. Herein, we leveraged the inherent drug-loading capabilities and distinctive structural attributes of Spirulina platensis (SP) to formulate a novel microalgae embolic agent, doxorubicin loaded-Spirulina platensis (DOX-SP). The DOX-SP formulation exhibited a notable capacity for drug loading and demonstrated the ability to sustain drug release in response to acidic tumor microenvironments (TME). The spiral structure and micron-scale size of SP contributed to effective vascular embolization and continuous localized release of DOX. Furthermore, the biodegradability of SP as a natural biomaterial ensured good biosafety, with its degradation products potentially enhancing the pH of TME. In a rat model of in-situ hepatocellular carcinoma, DOX-SP effectively suppressed tumor growth and significantly reduced tumor size following intra-arterial injection, while exhibiting minimal adverse effects. Taken together, the high drug loading capacity, effective vascular embolization, pH sensitivity, TME pH modulation, and biodegradability of DOX-SP made it a promising embolic agent for hepatocellular carcinoma treatment.