Self-Targeted Co-Delivery of an Antibiotic and a Cancer-Chemotherapeutic from Synthetic Liposomes for the Treatment of Infected Tumors
作者:
Wang, DY (Wang, Da-Yuan) [1] , [2] , [3] ; Cao, YL (Cao, Yuanlong) [1] , [2] , [3] ; Yang, G (Yang, Guang) [1] , [2] , [3] ; Zhang, SY (Zhang, Siyu) [1] ; van der Mei, HC (van der Mei, Henny C.) [2] , [3] ; Ren, YJ (Ren, Yijin) [4] , [5] ; van Kooten, TG (van Kooten, Theo G.) [2] , [3] ; de Groot, DJA (de Groot, Derk-Jan A.) [4] , [6] ; de Haan, JJ (de Haan, Jacco J.) [4] , [6] ; Shi, LQ (Shi, Linqi) [1] ; Busscher, HJ (Busscher, Henk J.) [2] , [3]
DOI
10.1002/adfm.202215153
在线发表
APR 2023
已索引
2023-05-05
文献类型
Article; Early Access
摘要
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-H2O 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.