Hepatocellular carcinoma (HCC) poses a serious threat to human health, underscoring the need for highly efficient local drug delivery systems. Kiwifruit-derived exosome-like nanovesicles (KELNs) were isolated via differential ultracentrifugation, characterized by saucer-shaped vesicles with a diameter of 145 nm, Zeta potential −13.7 ± 0.04 mV, and a glycerophospholipid bilayer. Hydrophobic drug resveratrol (Res) was loaded onto KELNs via co-incubation at 37 °C for 12 h under a 1:5 drug-to-carrier ratio (μg/μg), yielding KELNs-Res. This complex was in situ encapsulated within an injectable thermosensitive hydrogel (Gel) to form the nanocomposite Gel-KELNs-Res. This composite exhibits a rapid sol-gel transition at 36.5 ± 0.3 °C and possesses a porous microstructure. In vitro release experiments demonstrated sustained resveratrol release, with a cumulative release rate of 94.3% within 5 days. Compared to free Res, Gel-KELNs-Res significantly prolonged drug action time. It markedly inhibited HepG2 cell proliferation, migration, and invasion while significantly promoting apoptosis. This nanocomposite provides a strategy for sustained intratumoral Res delivery and holds promise as a local regional therapy for hepatocellular carcinoma.
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