Platelet-based biomimetic nanoparticle-loaded hydrogels targeting tumor angiogenesis and cancer stem cells to prevent postoperative hepatocellular carcinoma recurrence

Despite advancements in hepatocellular carcinoma (HCC) after surgical resection treatment, the persistence of residual tumors, liver cancer stem cells (LCSCs), and angiogenesis remains the primary reason for postoperative recurrence. Moreover, considering the low drug accumulation of traditional administration methods and the lack of enhanced permeability and retention (EPR) effect at the tumor site after HCC surgery, it is challenging in efficiently delivering drugs to the residual tumor site. Thus, platelet-based biomimetic nanoparticle-loaded thermosensitive hydrogels (B/S@PM-ZIF-8-Bsp/Gel) were developed, which not only had hemostatic function but also enhanced the adhesion at the surgical incisions of tumor due to Bletilla striata polysaccharide (Bsp) addition. The released B/S@PM-ZIF-8 from hydrogels could be actively recruited to surgical incisions by imitating the role of platelet. By application of B/S@PM-ZIF-8-Bsp/Gel, the combination of Bufalin (BFL) and Sorafenib (SFN) enhanced the inhibitory effects on the proliferation of tumor cells and LCSCs, and downregulated the expression of vascular endothelial growth factor (VEGF). Compared to multiple injection administrations of B/S@PM-ZIF-8, single-dose B/S@PM-ZIF-8-Bsp/Gel was more effective with average tumor fluorescence intensity 13.5 times lower than that of B/S@PM-ZIF-8, thus reducing the frequency of administration. The novel hydrogels were expected to offer an alternative treatment method for postoperative recurrence of HCC.