Enhanced anticancer efficacy of cantharidin by mPEG-PLGA micellar encapsulation: An effective strategy for application of a poisonous traditional Chinese medicine.

Cantharidin (CTD), the main active component of a poisonous traditional Chinese medicine (PTCM) Mylabris, exhibits highly effective therapy of hepatocellular carcinoma (HCC); however, the severe toxicity of CTD on the digestive and urinary systems prevents its clinical application. Here, CTD-loaded micelles (mPEG-PLGA-CTD) were prepared for enhancement of the antitumor efficacy and reduction of the toxicity of CTD. mPEG-PLGA-CTD comprised uniform spherical particles with particle size of 25.32 ± 1.25 nm and zeta potential of -5.70 ± 0.76 mV, exhibiting good stability and biocompatibility. mPEG-PLGA-CTD showed high toxicity on HepG2 cells by improving apoptosis and inhibiting protein phosphatases 2A (PP2A) compared to the low toxicity on l-02 hepatocytes. Intravenous injection of mPEG-PLGA-CTD led to a long circulation half-life of drugs, enhanced drug accumulation in the tumor tissues, and reduced drug accumulation in the other organs (e.g., the kidney) due to the enhanced permeability and retention effect compared to injection of free CTD; more importantly, the highly efficient antitumor effect and low systemic toxicity were achieved. A micellar formulation is very useful for enhancement of therapeutic efficacy and reduction of systemic toxicity of PTCMs.