Artesunate-loaded porous PLGA microsphere as a pulmonary delivery system for the treatment of non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) has emerged to be a significant cause of cancer mortality worldwide. Artesunate (ART) extracted from Chinese herb Artemisia annua L, has been proven to possess desirable anti-cancer efficacy, especially for the metastatic NSCLC treatment. Moreover, the poly(lactic-co-glycolic acid) (PLGA) microsphere has been considered to be a potential pulmonary delivery system for the sustained drug release to enhance the therapeutic efficacy of lung cancer. Herein, the ART-loaded porous PLGA microsphere was prepared through the emulsion solvent evaporation approach. The microsphere was demonstrated to possess highly porous structure and ideal aerodynamic diameter for the pulmonary administration. Meanwhile, sustained ART release was obtained from the porous microsphere within 8 days. The release solution collected from the microsphere could be effectively uptake by the cells and further induce the cell apoptosis and the cell cycle arrest at G2/M phase to execute the anti-proliferative effect, using human lung adenocarcinoma cell line A549 as a model. Additionally, strong inhibitory effect on the cell migration and invasion could be obtained after the treatment with release solution. Taken together, our results demonstrated that the ART-loaded PLGA porous microsphere could achieve excellent anti-cancer efficacy, providing a potential approach for the NSCLC treatment via the pulmonary administration.

Dual ATP/reduction-responsive polyplex to achieve the co-delivery of doxorubicin and miR-23b for the cancer treatment.

Combination therapy based on the co-delivery of therapeutic genes and anti-cancer drugs has emerged as a promising approach in the cancer treatment, and stimuli-responsive delivery systems could further improve the therapeutic efficacy. Herein, an ATP aptamer and its complementary DNA were used to form Duplex into which doxorubicin (DOX) was loaded to construct DOX-Duplex, and then the lipoic acid-modified oligoethyleneimine (LA-OEI) was employed as a carrier to realize the co-delivery of DOX-Duplex and miR-23b. The ternary nanocomplex LA-OEI/miR-23b/DOX-Duplex showed excellent anti-proliferative effect by inducing the cell apoptosis via mitochondrial signaling pathway and arresting the cell cycle at S phase. Meanwhile, the co-delivery of DOX-Duplex and miR-23b could efficiently inhibit the metastasis of cancer cells by reducing the expression level of MMP-9. The favorable anti-tumor efficacy of ternary nanocomplex was attributed to the rapid drug release in response to intracellular ATP concentration and reduction conditions and the synergistic effect between DOX-Duplex and miR-23b. Thus, ATP aptamer and reduction-responsive polymer provided a convenient platform to construct dual stimuli-responsive systems for the co-delivery of gene and drug in the cancer treatment.