Self‐Targeted Co‐Delivery of an Antibiotic and a Cancer‐Chemotherapeutic from Synthetic Liposomes for the Treatment of Infected Tumors
Da‐Yuan Wang, Y. Cao, Guang Yang, Siyu Zhang, Henny C. van der Mei, Yijin Ren, Theo G. van Kooten, Derk‐Jan A. de Groot, Jacco J. de Haan, Linqi Shi, Henk J. Busscher
Abstract
Abstract Intra‐tumor bacteria promote tumor growth and inactivate cancer‐chemotherapeutics, causing poor treatment prognoses. Combined administration of cancer‐chemotherapeutics and antibiotics may disturb the oral and intestinal microflora in critically‐ill patients. To establish intra‐tumor co‐delivery of cancer‐chemotherapeutics and antibiotics, gemcitabine and ciprofloxacin are loaded in so‐called “self‐targeting”, highly blood‐compatible, synthetic DCPA‐H 2 O liposomes equipped with complexed water for pH‐responsiveness. Liposomal pH‐responsiveness can be maintained by in‐shell loading of gemcitabine and in‐core loading of ciprofloxacin. These dual‐loaded liposomes are stealthily transported in the blood circulation to accumulate in the acidic environment of an infected tumor. Upon tumor self‐targeting, liposomes are fused with tumor cells and infecting bacteria and are disassembled to simultaneously release gemcitabine and ciprofloxacin. Treatment of mice with these self‐targeting liposomes yields significantly higher responses of Escherichia coli infected tumors with respect to both infection and tumor volume than gemcitabine and ciprofloxacin co‐delivered from non‐self‐targeting liposomes or free gemcitabine with or without ciprofloxacin in solution.