A novel GSH responsive poly(alpha-lipoic acid) nanocarrier bonding with the honokiol-DMXAA conjugate for combination therapy

The key to improve the therapeutic efficacy for cancer treatment is to increase the delivery of drugs to tumors. For this purpose, tumor-microenvironment stimuli-responsive materials have great potential. Here, we prepared a new nanomedicine by bonding the conjugate of honokiol (HNK) and 5,6-dimethylxanthenone-4-acetic acid (DMXAA) to a glutathione (GSH)-responsive nanocarrier, poly(alpha-lipoic acid) polyethylene glycol. The nanomedicine would disintegrate due to the high level of GSH at the tumor sites, achieving the co-delivery of HNK and DMXAA, and realizing the combination therapy through close-range killing by HNK and long-range striking by DMXAA together. In a murine 4T1 breast tumor model, this strategy exhibited high tumor inhibition rate of 93%, and provided a valuable therapeutic choice for cancer therapy.