Trypsin-instructed bioactive peptide nanodrugs with cascading transformations to improve chemotherapy against colon cancer
Abstract Chemotherapy remains an effective treatment for colon cancer but is hampered by its limited response rate. Bioactive peptides, marked with intracellular transformations, have been reported as an effective approach to boosting chemotherapeutic activity. Herein, a promising trypsin-responsive...
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| Format: | Article |
| Language: | English |
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BMC
2025-01-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-025-03143-1 |
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| author | Can Wu Xiao Wei Zhang Manman Wang Jinpan Sun Jianfei Chen Yanbin Guan Xin Pang |
| author_facet | Can Wu Xiao Wei Zhang Manman Wang Jinpan Sun Jianfei Chen Yanbin Guan Xin Pang |
| author_sort | Can Wu |
| collection | DOAJ |
| description | Abstract Chemotherapy remains an effective treatment for colon cancer but is hampered by its limited response rate. Bioactive peptides, marked with intracellular transformations, have been reported as an effective approach to boosting chemotherapeutic activity. Herein, a promising trypsin-responsive bioactive peptide-based nanodrug is constructed, which could significantly prolong the drug retention time in vivo by cascading transformations and improve chemotherapeutic efficacy. Initially, 1-Pept co-assembles with Dox into a few nanofibers called 1-Pept/Dox NFs, inducing an enhanced cellular uptake via caveolae-mediated endocytosis by avoiding lysosomal degradation and further promoting perinuclear transportation, thus enlarging the drug efficacy in target areas. After nanofiber disassembly, the released 1-Pept converts into Pept under the catalysis of intracellular overexpressed trypsin, which then reassembles into denser Pept NFs, inducing a cascade of effects including disruption of the cytoskeleton, mitochondrial dysfunction, and activation of caspase-3. By the synergism of Pept NFs and Dox, caspase-3 can be further activated, and cause greater damage to nuclear, thereby leading to tumor ablation. As the first example of employing trypsin-mediated nanodrugs with cascading transformations to promote chemotherapeutic activity, this work promises a strategy for novel therapies for efficiently combating colon cancer. Graphical Abstract |
| format | Article |
| id | doaj-art-06579702cde74d4cb893c0ad2fcc5d1a |
| institution | Kabale University |
| issn | 1477-3155 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj-art-06579702cde74d4cb893c0ad2fcc5d1a2025-02-02T12:41:00ZengBMCJournal of Nanobiotechnology1477-31552025-01-0123112010.1186/s12951-025-03143-1Trypsin-instructed bioactive peptide nanodrugs with cascading transformations to improve chemotherapy against colon cancerCan Wu0Xiao Wei Zhang1Manman Wang2Jinpan Sun3Jianfei Chen4Yanbin Guan5Xin Pang6School of Pharmacy, Henan University of Chinese MedicineCollaborative Innovation Center of Research and Development on the Whole Industry Chain of Yu-Yao, Henan University of Chinese MedicineSchool of Pharmacy, Henan University of Chinese MedicineSchool of Pharmacy, Henan University of Chinese MedicineSchool of Pharmacy, Henan University of Chinese MedicineSchool of Pharmacy, Henan University of Chinese MedicineSchool of Pharmacy, Henan University of Chinese MedicineAbstract Chemotherapy remains an effective treatment for colon cancer but is hampered by its limited response rate. Bioactive peptides, marked with intracellular transformations, have been reported as an effective approach to boosting chemotherapeutic activity. Herein, a promising trypsin-responsive bioactive peptide-based nanodrug is constructed, which could significantly prolong the drug retention time in vivo by cascading transformations and improve chemotherapeutic efficacy. Initially, 1-Pept co-assembles with Dox into a few nanofibers called 1-Pept/Dox NFs, inducing an enhanced cellular uptake via caveolae-mediated endocytosis by avoiding lysosomal degradation and further promoting perinuclear transportation, thus enlarging the drug efficacy in target areas. After nanofiber disassembly, the released 1-Pept converts into Pept under the catalysis of intracellular overexpressed trypsin, which then reassembles into denser Pept NFs, inducing a cascade of effects including disruption of the cytoskeleton, mitochondrial dysfunction, and activation of caspase-3. By the synergism of Pept NFs and Dox, caspase-3 can be further activated, and cause greater damage to nuclear, thereby leading to tumor ablation. As the first example of employing trypsin-mediated nanodrugs with cascading transformations to promote chemotherapeutic activity, this work promises a strategy for novel therapies for efficiently combating colon cancer. Graphical Abstracthttps://doi.org/10.1186/s12951-025-03143-1Bioactive peptideCascading transformationsChemotherapyTrypsinColon cancer |
| spellingShingle | Can Wu Xiao Wei Zhang Manman Wang Jinpan Sun Jianfei Chen Yanbin Guan Xin Pang Trypsin-instructed bioactive peptide nanodrugs with cascading transformations to improve chemotherapy against colon cancer Journal of Nanobiotechnology Bioactive peptide Cascading transformations Chemotherapy Trypsin Colon cancer |
| title | Trypsin-instructed bioactive peptide nanodrugs with cascading transformations to improve chemotherapy against colon cancer |
| title_full | Trypsin-instructed bioactive peptide nanodrugs with cascading transformations to improve chemotherapy against colon cancer |
| title_fullStr | Trypsin-instructed bioactive peptide nanodrugs with cascading transformations to improve chemotherapy against colon cancer |
| title_full_unstemmed | Trypsin-instructed bioactive peptide nanodrugs with cascading transformations to improve chemotherapy against colon cancer |
| title_short | Trypsin-instructed bioactive peptide nanodrugs with cascading transformations to improve chemotherapy against colon cancer |
| title_sort | trypsin instructed bioactive peptide nanodrugs with cascading transformations to improve chemotherapy against colon cancer |
| topic | Bioactive peptide Cascading transformations Chemotherapy Trypsin Colon cancer |
| url | https://doi.org/10.1186/s12951-025-03143-1 |
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