An alternative way to break the matrix barrier: an experimental study of a LIFU-mediated, visualizable targeted nanoparticle synergistic amplification for the treatment of malignant fibroblasts
Malignant fibroblasts (MFs) are widely present in various diseases and are characterized by connective tissue proliferation; these cells act as a physical barrier that severely limits drug delivery and affects disease outcomes. Based on this, we constructed the smart, integrated, theranostic, target...
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Frontiers Media S.A.
2024-11-01
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| Series: | Frontiers in Bioengineering and Biotechnology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fbioe.2024.1486369/full |
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| author | Xiangzhi Zhao Zhengchao Fan Junan Zhou Ying Li Weiwei Zhu Song Su Jizhu Xia |
| author_facet | Xiangzhi Zhao Zhengchao Fan Junan Zhou Ying Li Weiwei Zhu Song Su Jizhu Xia |
| author_sort | Xiangzhi Zhao |
| collection | DOAJ |
| description | Malignant fibroblasts (MFs) are widely present in various diseases and are characterized by connective tissue proliferation; these cells act as a physical barrier that severely limits drug delivery and affects disease outcomes. Based on this, we constructed the smart, integrated, theranostic, targeted lipid nanoprobe HMME-RG3@PFH to overcome the bottleneck in the early diagnosis and treatment of MF-related diseases. The protein glucose transporter protein 1 (GLUT-1) is overexpressed on MFs, and its ideal substrate, ginsenoside RG3 (RG3), significantly enhances the targeted uptake of HMME-RG3@PFH by MFs in a hypoxic environment and endows the nanomaterial with stealthiness to prolong its circulation. Perfluorohexane (PFH), a substance that can undergo phase change, was encapsulated in the lipid core and vaporized for ultrasound-enhanced imaging under low-intensity focused ultrasound (LIFU) irradiation. Moreover, hematoporphyrin monomethyl ether (HMME) was loaded into the lipid bilayer for photoacoustic molecular imaging and sonodynamic therapy (SDT) of MFs under the combined effects of LIFU. Additionally, HMME-RG3@PFH instantaneously burst during visualization to promote targeted drug delivery. In addition, the increased number of exposed RG3 fragments can regulate the MFs to enter a quiescent state. Overall, this nanoplatform ultimately achieves dual-modal imaging with targeted and precise drug release for visualization and synergistic amplification therapy, providing a new possibility for the early diagnosis and precise treatment of MF-related diseases. |
| format | Article |
| id | doaj-art-1b21c50d24e145dabbf64b8024f1709e |
| institution | OA Journals |
| issn | 2296-4185 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Bioengineering and Biotechnology |
| spelling | doaj-art-1b21c50d24e145dabbf64b8024f1709e2025-08-20T02:26:38ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852024-11-011210.3389/fbioe.2024.14863691486369An alternative way to break the matrix barrier: an experimental study of a LIFU-mediated, visualizable targeted nanoparticle synergistic amplification for the treatment of malignant fibroblastsXiangzhi Zhao0Zhengchao Fan1Junan Zhou2Ying Li3Weiwei Zhu4Song Su5Jizhu Xia6Department of Ultrasound, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, ChinaDepartment of Ultrasound, Sichuan Provincial Second Hospital of Traditional Chinese Medicine, Chengdu, Sichuan, ChinaDepartment of General Surgery (Hepatobiliary Surgery), The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, ChinaDepartment of Plastic and Burns Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, ChinaDepartment of Ultrasound, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, ChinaDepartment of General Surgery (Hepatobiliary Surgery), The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, ChinaDepartment of Ultrasound, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, ChinaMalignant fibroblasts (MFs) are widely present in various diseases and are characterized by connective tissue proliferation; these cells act as a physical barrier that severely limits drug delivery and affects disease outcomes. Based on this, we constructed the smart, integrated, theranostic, targeted lipid nanoprobe HMME-RG3@PFH to overcome the bottleneck in the early diagnosis and treatment of MF-related diseases. The protein glucose transporter protein 1 (GLUT-1) is overexpressed on MFs, and its ideal substrate, ginsenoside RG3 (RG3), significantly enhances the targeted uptake of HMME-RG3@PFH by MFs in a hypoxic environment and endows the nanomaterial with stealthiness to prolong its circulation. Perfluorohexane (PFH), a substance that can undergo phase change, was encapsulated in the lipid core and vaporized for ultrasound-enhanced imaging under low-intensity focused ultrasound (LIFU) irradiation. Moreover, hematoporphyrin monomethyl ether (HMME) was loaded into the lipid bilayer for photoacoustic molecular imaging and sonodynamic therapy (SDT) of MFs under the combined effects of LIFU. Additionally, HMME-RG3@PFH instantaneously burst during visualization to promote targeted drug delivery. In addition, the increased number of exposed RG3 fragments can regulate the MFs to enter a quiescent state. Overall, this nanoplatform ultimately achieves dual-modal imaging with targeted and precise drug release for visualization and synergistic amplification therapy, providing a new possibility for the early diagnosis and precise treatment of MF-related diseases.https://www.frontiersin.org/articles/10.3389/fbioe.2024.1486369/fullsonodynamic therapyMalignant fibroblastshematoporphyrin monomethyl etherginsenoside RG3dual-modal imaginglow-intensity focused ultrasound |
| spellingShingle | Xiangzhi Zhao Zhengchao Fan Junan Zhou Ying Li Weiwei Zhu Song Su Jizhu Xia An alternative way to break the matrix barrier: an experimental study of a LIFU-mediated, visualizable targeted nanoparticle synergistic amplification for the treatment of malignant fibroblasts Frontiers in Bioengineering and Biotechnology sonodynamic therapy Malignant fibroblasts hematoporphyrin monomethyl ether ginsenoside RG3 dual-modal imaging low-intensity focused ultrasound |
| title | An alternative way to break the matrix barrier: an experimental study of a LIFU-mediated, visualizable targeted nanoparticle synergistic amplification for the treatment of malignant fibroblasts |
| title_full | An alternative way to break the matrix barrier: an experimental study of a LIFU-mediated, visualizable targeted nanoparticle synergistic amplification for the treatment of malignant fibroblasts |
| title_fullStr | An alternative way to break the matrix barrier: an experimental study of a LIFU-mediated, visualizable targeted nanoparticle synergistic amplification for the treatment of malignant fibroblasts |
| title_full_unstemmed | An alternative way to break the matrix barrier: an experimental study of a LIFU-mediated, visualizable targeted nanoparticle synergistic amplification for the treatment of malignant fibroblasts |
| title_short | An alternative way to break the matrix barrier: an experimental study of a LIFU-mediated, visualizable targeted nanoparticle synergistic amplification for the treatment of malignant fibroblasts |
| title_sort | alternative way to break the matrix barrier an experimental study of a lifu mediated visualizable targeted nanoparticle synergistic amplification for the treatment of malignant fibroblasts |
| topic | sonodynamic therapy Malignant fibroblasts hematoporphyrin monomethyl ether ginsenoside RG3 dual-modal imaging low-intensity focused ultrasound |
| url | https://www.frontiersin.org/articles/10.3389/fbioe.2024.1486369/full |
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