Accurate delivery of pristimerin and paclitaxel by folic acid-linked nano-micelles for enhancing chemosensitivity in cancer therapy.

Chemoresistance remains a huge challenge for effective treatment of non-small cell lung cancer (NSCLC). Previous studies have shown Chinese herbal extracts possess great potential in ameliorating tumor chemoresistance, however, the efficacy is clinically limited mainly because of the poor tumor-targeting and in vivo stability. The construction of nano-delivery systems for herbal extracts has been shown to improve drug targeting, enhance therapeutic efficacy and reduce toxic and side effects. In this study, a folic acid (FA)-modified nano-herb micelle was developed for codelivery of pristimerin (PRI) and paclitaxel (PTX) to enhance chemosensitivity of NSCLC, in which PRI could synergistically enhance PTX-induced growth inhibition of A549 cancer cell. PTX was firstly grafted with the FA-linked polyethylene glycol (PEG) and then encapsulated with PRI to construct the PRI@FA-PEG-PTX (P@FPP) nano-micelles (NMs), which exhibited improved tumor-targeting and in vivo stability. This active-targeting P@FPP NMs displayed excellent tumor-targeting characteristics without obvious toxicity. Moreover, inhibition of tumor growth and metastasis induced by P@FPP NMs were significantly enhanced compared with the combined effects of the two drugs (PRI in combination of PTX), which associated with epithelial mesenchymal transition inhibition to some extent. Overall, this active-targeting NMs provides a versatile nano-herb strategy for improving tumor-targeting of Chinese herbal extracts, which may help in the promotion of enhancing chemosensitivity of NSCLC in clinical applications.