Paclitaxel-in-liposome-in-bacteria for inhalation treatment of primary lung cancer

Abstract

Bacterial therapy is emerging for the treatment of cancers though some scientific and clinical problems have not been addressed. Here, a live drug-loaded carrier, paclitaxel-in-liposome-in-bacteria (LPB), was prepared for inhalation treatment of primary lung cancer, where liposomal paclitaxel (LP) was highly effectively internalized into bacteria (E. coli or L. casei) to get LP-in-E. coli (LPE) or LP-in-L. casei (LPL) by electroporation that had no influence on the growth of these bacteria. Bacteria, LP, the simple mixture of LP and bacteria, and LPB remarkably inhibited the proliferation of A549 lung cancer cells, where LPE was the strongest one. Drug-loaded bacteria delivered the cargos into the cells more quickly than the mixture of drugs and bacteria and the cargos alone. LPE also showed the highest anticancer effect on the rat primary lung cancer among them with the downregulation of VEGF and HIF-1α and the improvement of cancer cell apoptosis after intratracheal administration. Moreover, the bacterial formulations significantly enhanced the expressions of immune markers (TNF-α, IL-4, and IFN-γ) and immune cells (leukocytes and neutrophils). LPB showed much higher bacterial distribution in the lung than other organs after intratracheal administration. LPB is a promising medicine for inhalation treatment of primary lung cancer.

Keywords: Escherichia coli; Inhalation; Lactobacillus casei; Liposome; Lung cancer; Paclitaxel; Paclitaxel (PubChem CID: 36314).