A Dual Drug Delivery Platform for Cancer-Bacteria Cotargeting

Bacteria can associate with mammalian cells in different ways. While some are essential for the body, others can manipulate their local environment to cause tumor-like conditions or find refuge in already existing cancerous tissues or cells, impacting not only chemotherapy through drug transformation but also antibiotic resistance through immune evasion. Despite these facts, cancer and bacterial therapies continue to be administered independently. We have developed a dual drug delivery platform, called "dualosome", that not only targets cancer cells but also clears bacteria from the cancer niche. Dualosomes comprise liposomes loaded with an anticancer drug (doxorubicin) in their core and a cationic antibacterial peptide (sushi S3) on their surface. Folic acid is also attached to the liposomal surface to impart cancer cell specificity. The efficacy of dualosomes is demonstrated on model S. typhi-infected hepatoma (Huh-7) cells, and it shows that the copackaged system is at least 75% more effective in eliminating both cell types than either drug alone, in the nanoformulated or free form. This improved performance is attributed to the bacteria-linked doxorubicin activity, as well as the enhanced internalization of the liposomes due to their cationic surface charge. Overall, our system holds great promise for curbing cancer-related bacterial infections and drug resistance in both cell types.