Prodigiosin-functionalized Lactobacillus acidophilus ghost: A bioinspired combination against colorectal cancer cells

Abstract

Lactobacillus acidophilus ghosts (LAGs) with the unique safety of a probiotic, inherent tropism for colon cells and multiple bioactivities offer great promise as drug carrier for colon targeting. We report herein on a novel bioinspired drug delivery system against colorectal cancer (CRC) cells based on LAGs functionalized with prodigiosin (PG), a proapoptotic bacterial metabolite. LAGs were prepared by a chemical method and highly purified by density gradient centrifugation. Multiple microscopic and staining techniques characterized LAGs by a relatively small size, size uniformity, a relatively large internal volume devoid of cytoplasmic and genetic materials and an intact negatively charged envelop. PG was highly bound to LAGs cell wall, generating a physiologically stable bioactive entity (PG-LAGs) active against HCT116 CRC cells at the cellular and molecular levels. Cell viability data underlined cytotoxicity of PG and LAGs and LAGs-induced enhancement of PG selectivity for HCT116 cells. Combination and Dose reduction indices anticipating dose reduction of PG and LAGs. Molecularly, PG-LAGs significantly modulated the expression of apoptosis-related biomarkers, caspase 3, P53 and BCL2, in favor of cytotoxicity against HCT116 cells relative to PG and 5-fluorouracil. Accordingly, LAGs offer promise as novel drug carrier for targeted colon delivery and PG-LAGs may bring therapeutic benefits in colorectal carcinoma.