Identification of a VEGFR-3 binding peptide TMVP1 for enhancing drug delivery efficiency and therapeutic efficacy against tumor lymphangiogensis
Abstract VEGFR-3 plays an indispensable role in lymphangiogenesis. Previous findings suggest that blocking the VEGFR-3 signaling pathway can inhibit lymph node metastasis effectively, thus reduce the incidence of distant metastasis. The development of new VEGFR-3 targeting drugs for early detection and effective treatments is, therefore, urgently requied. Here, in vitro biopanning of a phage-displayed peptide library was used to identify specific peptides binding to the extracellular domain of VEGFR-3. We obtained a novel VEGFR-3 targeting peptide TMVP1 (LARGR), our combined immunofluorescence and radiopharmaceutical studies revealed that FITC-TMVP1 and 99mTc-labeled TMVP1 specifically accumulated in VEGFR-3 positive lymphatic vessels of tumors after i.v administration in tumor xenograft models in vivo. The accumulation of the TMVP1 in lymphatic vessels was specific, because this accumulation can be significantly reduced by blocking experiments. To enhance the therapeutic efficacy of anticancer drugs, we fused TMVP1 to a proapoptotic peptide D(KLAKLAK)2, the fusion peptide strongly inhibited tumor lymphangiogenesis in vitro and in vivo, and specifically suppressed lung metastasis in a 4T1 breast cancer xenograft model. Our results suggest that TMVP1 is a promising therapeutic strategy for the development of new diagnostic tracers or alternative anticancer agents for tumor lymphangiogenesis and lymphatic metastasis..
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Preprint| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
ResearchSquare.com - (2022) vom: 20. Apr. Zur Gesamtaufnahme - year:2022 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Fan, Liangsheng [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.21203/rs.3.rs-1517169/v1 |
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| funding: |
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| 245 | 1 | 0 | |a Identification of a VEGFR-3 binding peptide TMVP1 for enhancing drug delivery efficiency and therapeutic efficacy against tumor lymphangiogensis |
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| 520 | |a Abstract VEGFR-3 plays an indispensable role in lymphangiogenesis. Previous findings suggest that blocking the VEGFR-3 signaling pathway can inhibit lymph node metastasis effectively, thus reduce the incidence of distant metastasis. The development of new VEGFR-3 targeting drugs for early detection and effective treatments is, therefore, urgently requied. Here, in vitro biopanning of a phage-displayed peptide library was used to identify specific peptides binding to the extracellular domain of VEGFR-3. We obtained a novel VEGFR-3 targeting peptide TMVP1 (LARGR), our combined immunofluorescence and radiopharmaceutical studies revealed that FITC-TMVP1 and 99mTc-labeled TMVP1 specifically accumulated in VEGFR-3 positive lymphatic vessels of tumors after i.v administration in tumor xenograft models in vivo. The accumulation of the TMVP1 in lymphatic vessels was specific, because this accumulation can be significantly reduced by blocking experiments. To enhance the therapeutic efficacy of anticancer drugs, we fused TMVP1 to a proapoptotic peptide D(KLAKLAK)2, the fusion peptide strongly inhibited tumor lymphangiogenesis in vitro and in vivo, and specifically suppressed lung metastasis in a 4T1 breast cancer xenograft model. Our results suggest that TMVP1 is a promising therapeutic strategy for the development of new diagnostic tracers or alternative anticancer agents for tumor lymphangiogenesis and lymphatic metastasis. | ||
| 700 | 1 | |a Cheng, Teng |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Fei |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Zhenzhong |e verfasserin |4 aut | |
| 700 | 1 | |a Dong, Qingjian |e verfasserin |4 aut | |
| 700 | 1 | |a Yuan, Yuan |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Xi |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Ying |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Xiaohua |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Ding |e verfasserin |4 aut | |
| 700 | 1 | |a Xi, Ling |e verfasserin |4 aut | |
| 700 | 1 | |a Luo, Danfeng |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Xiangyi |e verfasserin |4 aut | |
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