Self-Targeted Co-Delivery of an Antibiotic and a Cancer-Chemotherapeutic from Synthetic Liposomes for the Treatment of Infected Tumors

Da Yuan Wang, Yuanlong 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*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

9 Citations (Scopus)
35 Downloads (Pure)

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-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.

Original languageEnglish
Article number2215153
Number of pages14
JournalAdvanced Functional Materials
Volume33
Issue number32
Early online dateApr-2023
DOIs
Publication statusPublished - 8-Aug-2023

Keywords

  • antibiotics
  • chemotherapeutics
  • gemcitabine
  • infections
  • membrane fusion
  • nanoparticles
  • tumor treatments
  • Zeta potentials

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