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

Abstract

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.

Tumor Microenvironment Responsive Nanomicelle with Folic Acid Modification Co-Delivery of Doxorubicin/Shikonin for Triple Negative Breast Cancer Treatment

“…The synthesis of folic acid grafted polyethylene glycol carboxyl (FA-PEG-COOH) was performed according to methods in a previous study [ 12 ]. In short, 1 g of FA and 1 g of EDCI were added into 30 mL DMSO and activated at 40 °C for 30 min.…”

“…Folic acid-grafted polyethylene glycol-doxorubicin (FA-PEG-DOX) was synthetized similar to the methods in reference [ 12 ]. A total of 0.1 g of DOX with 0.20 g of CDI, 0.2 g of DOX with 0.4 g of CDI, and 0.3 g of DOX with 0.6 g of CDI were dissolved in 10 mL DMSO and stirred at 40 °C for 4 h, respectively.…”

“…At present, the liposomes are the only types of nano drugs that have been applied in clinical use. Nanomicelles (NMs) exhibit structures and low molecular weights that are similar to those of liposomes, especially polyethylene glycol (PEG) micelles [ 11 , 12 ]. PEG micelles are usually composed of PEG-grafted ligands and drugs, which can provide higher drug loading [ 13 , 14 ] with simple structures.…”

Innovative Encapsulation Strategies for Food, Industrial, and Pharmaceutical Applications

“…P@FPP nano-micelles (NMs) greatly improved upon the combination potential of the two free drugs (PRI in conjunction with PTX) in terms of inhibiting tumor growth and metastasis. [171] In cervical cancer HeLa cells, PTXloaded PEG-b-PLA/zein NPs showed greater sustained release and cancer cell killing efficiency. Additionally, in a murine xenograft tumor model, PTX-NPs exhibited excellent biosafety and outstanding anti-tumor activity.…”

“…Moreover, co‐delivery of PTX and pristimerin (PRI) in nano‐micelles (PRI@FA‐PEG‐PTX (P@FPP)) effectively targeted tumor without notable toxicity. P@FPP nano‐micelles (NMs) greatly improved upon the combination potential of the two free drugs (PRI in conjunction with PTX) in terms of inhibiting tumor growth and metastasis [171] . In cervical cancer HeLa cells, PTX‐loaded PEG‐b‐PLA/zein NPs showed greater sustained release and cancer cell killing efficiency.…”