1. Three-in-One Peptide Prodrug with Targeting, Assembly and Release Properties for Overcoming Bacterium-Induced Drug Resistance and Potentiating Anti-Cancer Immune Response.
- Author
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Gao G, Jiang YW, Chen J, Xu X, Sun X, Xu H, Liang G, Liu X, Zhan W, Wang M, Xu Y, Zheng J, and Wang G
- Subjects
- Humans, Cell Line, Tumor, Drug Resistance, Neoplasm drug effects, Animals, Immunotherapy, Peptides chemistry, Peptides pharmacology, Camptothecin pharmacology, Camptothecin chemistry, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents chemistry, Mice, Nanofibers chemistry, Ciprofloxacin pharmacology, Ciprofloxacin chemistry, Drug Liberation, Biotin chemistry, Prodrugs chemistry, Prodrugs pharmacology, Antineoplastic Agents chemistry, Antineoplastic Agents pharmacology, Colorectal Neoplasms drug therapy
- Abstract
The presence of bacteria in tumor results in chemotherapeutic drug resistance and weakens the immune response in colorectal cancer. To overcome bacterium-induced chemotherapeutic drug resistance and potentiate antitumor immunity, herein a novel molecule Biotin-Lys(SA-Cip-OH)-Lys(SA-CPT)-Phe-Phe-Nap (Biotin-Cip-CPT-Nap) is rationally designed containing four functional motifs (i.e., a biotin motif for targeting, Phe-Phe(-Nap) motif for self-assembly, ciprofloxacin derivative (Cip-OH) motif for antibacterial effect, and camptothecin (CPT) motif for chemotherapy). Using the designed molecule, a novel strategy of intracellular enzymatic nanofiber formation and synergistic antibacterium-enhanced chemotherapy and immunotherapy is achieved. Under endocytosis mediated by highly expressed biotin receptor in colorectal cancer cell membrane and the catalysis of highly expressed carboxylesterase in the cytoplasm, this novel molecule can be transformed into Biotin-Nap, which self-assembled into nanofibers. Meanwhile, antibiotic Cip-OH and chemotherapeutic drug CPT are released, overcoming bacterium-induced drug resistance and enhancing the therapeutic efficacy of immunotherapy towards colorectal cancer. This work offers a feasible strategy for the design of novel multifunctional prodrugs to improve the efficiency of colorectal cancer treatment., (© 2024 Wiley‐VCH GmbH.)
- Published
- 2024
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