Engineered Polymeric Nanovector for Intracellular Peptide Delivery in Antitumor Therapy
Xi Zhang,1,* Mingming Zhang,1,* Sijun Huang,1 Kiyoshi Ohtani,2 Li Xu,1 Yi Guo1 1Key Laboratory for Molecular Enzymology and Engineering, the Ministry of Education, National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, 130012, People’s...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2023-09-01
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| Series: | International Journal of Nanomedicine |
| Subjects: | |
| Online Access: | https://www.dovepress.com/engineered-polymeric-nanovector-for-intracellular-peptide-delivery-in--peer-reviewed-fulltext-article-IJN |
| _version_ | 1797678104887427072 |
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| author | Zhang X Zhang M Huang S Ohtani K Xu L Guo Y |
| author_facet | Zhang X Zhang M Huang S Ohtani K Xu L Guo Y |
| author_sort | Zhang X |
| collection | DOAJ |
| description | Xi Zhang,1,* Mingming Zhang,1,* Sijun Huang,1 Kiyoshi Ohtani,2 Li Xu,1 Yi Guo1 1Key Laboratory for Molecular Enzymology and Engineering, the Ministry of Education, National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, 130012, People’s Republic of China; 2Department of Biomedical Sciences, School of Biological and Environmental Sciences, Kwansei Gakuin University, Sanda, Hyogo, 669-1337, Japan*These authors contributed equally to this workCorrespondence: Li Xu; Yi Guo, Key Laboratory for Molecular Enzymology and Engineering, the Ministry of Education, National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, 130012, People’s Republic of China, Email xuli@jlu.edu.cn; guoyi@jlu.edu.cnObjective: This study aimed to deliver a polypeptide from the Bax-BH3 domain (BHP) through the synthesis of self-assembled amphiphile nanovectors (NVs) and to assess their potential for cancer therapeutic applications and biological safety in vitro and in vivo. These findings provide valuable options for cancer intervention and a novel approach for the rational design of therapeutics.Methods: We studied the antitumor activity of BHP by preparing RGDfK-PHPMA-b-Poly (MMA-alt-(Rhob-MA)) (RPPMMRA) and encapsulating it in BHP-NV. We also performed a series of characterizations and property analyses of RPPMMRA, including its size, stability, and drug-carrying capacity. The biocompatibility of RPPMMRA was evaluated in terms of cytotoxicity and hemolytic effects. The pro-apoptotic capacity of BHP was evaluated in vitro using mitochondrial membrane potential, flow cytometry, and apoptosis visualization techniques. The potential therapeutic effects of BHP on tumors were explored using reverse molecular docking. We also investigated the in vivo proapoptotic effect of BHP-NV in a nude mouse tumor model.Results: NVs were successfully prepared with hydrated particle sizes ranging from 189.6 nm to 256.6 nm, spherical overall, and were able to remain stable in different media for 72 h with drug loading up to 15.2%. The NVs were be successfully internalized within 6 h with good biocompatibility. Neither BHP nor NV showed significant toxicity when administered alone, however, BHP-NV demonstrated significant side effects in vitro and in vivo. The apoptosis rate increased significantly from 14.13% to 66.34%. Experiments in vivo showed that BHP-NV exhibited significant apoptotic and tumor-suppressive effects.Conclusion: A targeted fluorescent NV with high drug delivery efficiency and sustained release protected the active center of BHP, constituting BHP-NV for targeted delivery. RPPMMRA demonstrated excellent biocompatibility, stability, and drug loading ability, whereas and BHP-NV demonstrated potent antitumor effects in vivo and in vitro.Graphical Abstract: Keywords: HPMA copolymers, BH3 domain, pro-apoptotic, polypeptide drugs, RGDfK |
| first_indexed | 2024-03-11T22:54:50Z |
| format | Article |
| id | doaj.art-99bb18937ea14f349939f419370ff277 |
| institution | Directory Open Access Journal |
| issn | 1178-2013 |
| language | English |
| last_indexed | 2024-03-11T22:54:50Z |
| publishDate | 2023-09-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | International Journal of Nanomedicine |
| spelling | doaj.art-99bb18937ea14f349939f419370ff2772023-09-21T19:08:58ZengDove Medical PressInternational Journal of Nanomedicine1178-20132023-09-01Volume 185343536386791Engineered Polymeric Nanovector for Intracellular Peptide Delivery in Antitumor TherapyZhang XZhang MHuang SOhtani KXu LGuo YXi Zhang,1,* Mingming Zhang,1,* Sijun Huang,1 Kiyoshi Ohtani,2 Li Xu,1 Yi Guo1 1Key Laboratory for Molecular Enzymology and Engineering, the Ministry of Education, National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, 130012, People’s Republic of China; 2Department of Biomedical Sciences, School of Biological and Environmental Sciences, Kwansei Gakuin University, Sanda, Hyogo, 669-1337, Japan*These authors contributed equally to this workCorrespondence: Li Xu; Yi Guo, Key Laboratory for Molecular Enzymology and Engineering, the Ministry of Education, National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, 130012, People’s Republic of China, Email xuli@jlu.edu.cn; guoyi@jlu.edu.cnObjective: This study aimed to deliver a polypeptide from the Bax-BH3 domain (BHP) through the synthesis of self-assembled amphiphile nanovectors (NVs) and to assess their potential for cancer therapeutic applications and biological safety in vitro and in vivo. These findings provide valuable options for cancer intervention and a novel approach for the rational design of therapeutics.Methods: We studied the antitumor activity of BHP by preparing RGDfK-PHPMA-b-Poly (MMA-alt-(Rhob-MA)) (RPPMMRA) and encapsulating it in BHP-NV. We also performed a series of characterizations and property analyses of RPPMMRA, including its size, stability, and drug-carrying capacity. The biocompatibility of RPPMMRA was evaluated in terms of cytotoxicity and hemolytic effects. The pro-apoptotic capacity of BHP was evaluated in vitro using mitochondrial membrane potential, flow cytometry, and apoptosis visualization techniques. The potential therapeutic effects of BHP on tumors were explored using reverse molecular docking. We also investigated the in vivo proapoptotic effect of BHP-NV in a nude mouse tumor model.Results: NVs were successfully prepared with hydrated particle sizes ranging from 189.6 nm to 256.6 nm, spherical overall, and were able to remain stable in different media for 72 h with drug loading up to 15.2%. The NVs were be successfully internalized within 6 h with good biocompatibility. Neither BHP nor NV showed significant toxicity when administered alone, however, BHP-NV demonstrated significant side effects in vitro and in vivo. The apoptosis rate increased significantly from 14.13% to 66.34%. Experiments in vivo showed that BHP-NV exhibited significant apoptotic and tumor-suppressive effects.Conclusion: A targeted fluorescent NV with high drug delivery efficiency and sustained release protected the active center of BHP, constituting BHP-NV for targeted delivery. RPPMMRA demonstrated excellent biocompatibility, stability, and drug loading ability, whereas and BHP-NV demonstrated potent antitumor effects in vivo and in vitro.Graphical Abstract: Keywords: HPMA copolymers, BH3 domain, pro-apoptotic, polypeptide drugs, RGDfKhttps://www.dovepress.com/engineered-polymeric-nanovector-for-intracellular-peptide-delivery-in--peer-reviewed-fulltext-article-IJNhpma copolymersbh3 domainpro-apoptoticpolypeptide drugsrgdfk |
| spellingShingle | Zhang X Zhang M Huang S Ohtani K Xu L Guo Y Engineered Polymeric Nanovector for Intracellular Peptide Delivery in Antitumor Therapy International Journal of Nanomedicine hpma copolymers bh3 domain pro-apoptotic polypeptide drugs rgdfk |
| title | Engineered Polymeric Nanovector for Intracellular Peptide Delivery in Antitumor Therapy |
| title_full | Engineered Polymeric Nanovector for Intracellular Peptide Delivery in Antitumor Therapy |
| title_fullStr | Engineered Polymeric Nanovector for Intracellular Peptide Delivery in Antitumor Therapy |
| title_full_unstemmed | Engineered Polymeric Nanovector for Intracellular Peptide Delivery in Antitumor Therapy |
| title_short | Engineered Polymeric Nanovector for Intracellular Peptide Delivery in Antitumor Therapy |
| title_sort | engineered polymeric nanovector for intracellular peptide delivery in antitumor therapy |
| topic | hpma copolymers bh3 domain pro-apoptotic polypeptide drugs rgdfk |
| url | https://www.dovepress.com/engineered-polymeric-nanovector-for-intracellular-peptide-delivery-in--peer-reviewed-fulltext-article-IJN |
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