Synergistic Nanomedicine-Microcarrier for Transarterial Chemoembolization Against Hepatocellular Carcinoma
Qin Shi, Wen Zhang, Licheng Yang, Minjie Yang, Jingqin Ma, Jiaze Yu, Yongbin Cao, Jianjun Luo, Shengxiang Rao, Lingxiao Liu, Zhiping YanIntroduction:
Transarterial chemoembolization (TACE) has become a crucial treatment method for hepatocellular carcinoma (HCC) in recent years. However, its effect is limited by low sensitivity to chemotherapy and unsatisfactory loading performance of the embolic agent. This study aimed to explore a promising treatment strategy that combines nanomedicine with a microcarrier to enhance the efficacy of TACE.
Methods:
In this work, the porous microcarrier was used to carry doxorubicin-loaded zeolitic imidazolate framework-8 nanoparticles (M@ZIF-8-DOX) according to a conventional drug loading method. The physical and chemical properties were characterized. An in vitro cell assay was used to assess the cytotoxicity and cellular uptake ability of the embolic agent. To evaluate the antitumor performance and safety, the M@ZIF-8-DOX was delivered by the standard interventional procedure in the rabbit VX2 liver tumor model
Results:
The M@ZIF-8-DOX effectively slowed the release of DOX in the bloodstream and extended the blood circulation time. In vitro studies revealed that ZIF-8-DOX showed high tumor cellular uptake and increased the intracellular DOX concentration. Furthermore, it was observed that M@ZIF-8-DOX could significantly inhibit tumor growth and proliferation while promoting tumor cell necrosis. Safety evaluation further confirmed that the M@ZIF-8-DOX had negligible toxicity to major organs and hepatorenal function
Discussion:
The structures of the nanoparticles can be disrupted by the acidic and hypoxic tumor microenvironment to release drugs in a short time. They usually increase intracellular drug concentrations to improve chemotherapy sensitivity and reduce systemic toxicity. Moreover, the combination of embolic agents and nanomedicine has demonstrated an excellent synergistic effect, providing a new strategy for TACE.
Conclusion:
The M@ZIF-8-DOX is a simple and highly effective embolic agent for TACE, and the concept of nano platform synergistically enhanced embolization therapy may be profound effect in the development of nanodrugs for HCC.