Curcumin-loaded pH-responsive hybrid nanovesicles from Bergenia purpurascens root exosomes for synergistic lung cancer treatment.

Lung cancer, with its high incidence and mortality rates, urgently demands innovative therapeutic strategies to address the limitations of conventional treatments, such as nonspecific toxicity and the development of drug resistance. Plant-derived exosomes have recently emerged as promising natural nanocarriers, owing to their inherent biocompatibility, low immunogenicity, and intrinsic bioactive properties. In this work, a novel hybrid nanovesicle system (HNVs) was developed by fusing exosomes isolated from Bergenia purpurascens roots (BPR-Exos), which inherently inhibit tumor migration through the ID1-Snail pathway, with pH-sensitive liposomes. This design integrated the biological activity of BPR-Exos with the engineered capability of tumor-acid-responsive drug release. Upon encapsulation of the anticancer drug curcumin (Cur), HNVs@Cur demonstrated high encapsulation efficiency, potentiated cellular uptake, and sustained release. Both in vitro and in vivo studies showed that HNVs@Cur significantly suppressed the proliferation, migration, invasion of lung cancer cells, and inducing apoptosis. Furthermore, HNVs@Cur exhibited favorable tumor-targeting ability and biosafety. Taken together, this novel hybrid nanovesicle system represents a promising synergistic strategy for targeted lung cancer therapy, providing a valuable reference for further therapeutic development.