Three-in-One Peptide Prodrug with Targeting, Assembly and Release Properties for Overcoming Bacterium-Induced Drug Resistance and Potentiating Anti-Cancer Immune Response
© 2024 Wiley-VCH GmbH..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
Advanced materials (Deerfield Beach, Fla.) - (2024) vom: 05. März, Seite e2312153 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Gao, Ge [VerfasserIn] |
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| Links: |
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| Themen: |
Chemotherapeutic drug resistance |
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| Anmerkungen: |
Date Revised 13.03.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1002/adma.202312153 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM369340310 |
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| 520 | |a © 2024 Wiley-VCH GmbH. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a chemotherapeutic drug resistance | |
| 650 | 4 | |a enzymes | |
| 650 | 4 | |a immunotherapy | |
| 650 | 4 | |a peptides | |
| 650 | 4 | |a self-assembly | |
| 700 | 1 | |a Jiang, Yao-Wen |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Jiaxuan |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Xiaodi |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Xianbao |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Haidong |e verfasserin |4 aut | |
| 700 | 1 | |a Liang, Gaolin |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Xiaoyang |e verfasserin |4 aut | |
| 700 | 1 | |a Zhan, Wenjun |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Meng |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Yixin |e verfasserin |4 aut | |
| 700 | 1 | |a Zheng, Junnian |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Gang |e verfasserin |4 aut | |
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