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

Bacterial therapy is emerging for the treatment of cancers though some scientific and clinical problems have not been addressed. Here, a living 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 inhibit the proliferation of A549 lung cancer cells, where LPE is the strongest one. Drug-loaded bacteria can delivers the cargos into the cells more quickly than the mixture of drugs and bacteria and the cargos alone. LPE also shows 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. Moreover, the bacterial formulations significantly enhance the expressions of immune markers (TNF-α, IL-4, and IFN-γ) and immune cells (leukocytes and neutrophils). After inhalation to the rat lungs, LPB shows much higher bacterial distribution in the lung than other organs. LPB is a promising medicine for inhalation treatment of primary lung cancer.