A bioinspired stimuli-responsive amino acid-based antibacterial drug delivery system in cancer therapy

Abstract

The chronic bacterial inflammation triggered by microbiota is a well-established induction factor promoting colitis-associated colorectal cancer (CRC) and inflammatory bowel disease. Escherichia coli (E. coli) bacteria precisely involved in colon inflammation play a crucial role in promoting carcinogenesis. Herein, we report a combinatorial strategy to design an antibacterial drug delivery scaffold effective against E. coli able to deliver the anticancer drug doxorubicin in a stimuli-responsive manner. The living nature of reversible addition–fragmentation chain-transfer (RAFT) polymerization has been exploited for the formation of dual pH and temperature-responsive water-soluble diblock amphiphilic copolymers of poly(ethylene glycol methyl ether methacrylate) (PEGMA) and tyrosine. The self-assembled polymers exhibit significant changes in pH responsiveness, lower critical solution temperature (LCST) and hydrodynamic diameters upon polymerization and have been utilized for the delivery of the anticancer drug doxorubicin against a human hepatoma (HepG2) cell line. Upon delivery of the cargo material in acidic pH, the increment in surface charge of the material makes it active against bacteria. Such a combinational design of copolymers is expected to establish a new avenue for the use of bioresources in therapeutic applications.