TRPC6-targeted dexamethasone nanobubbles with ultrasound-guided theranostics for adriamycin-induced nephropathy
Abstract Background Glucocorticoid (GC) intolerance and systemic toxicity pose significant challenges in the treatment of primary nephrotic syndrome (PNS), underscoring the urgent need for targeted therapies that maximize efficacy while minimizing adverse effects. To address these challenges, we dev...
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BMC
2025-05-01
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| Series: | Journal of Nanobiotechnology |
| Online Access: | https://doi.org/10.1186/s12951-025-03487-8 |
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| author | Lin Wu Yang Liu Ziqi Fu Honglei Guo Kang Liu Jiafa Ren Zhimin Huang Fang Yang Huijuan Mao |
| author_facet | Lin Wu Yang Liu Ziqi Fu Honglei Guo Kang Liu Jiafa Ren Zhimin Huang Fang Yang Huijuan Mao |
| author_sort | Lin Wu |
| collection | DOAJ |
| description | Abstract Background Glucocorticoid (GC) intolerance and systemic toxicity pose significant challenges in the treatment of primary nephrotic syndrome (PNS), underscoring the urgent need for targeted therapies that maximize efficacy while minimizing adverse effects. To address these challenges, we developed TRPC6-targeted dexamethasone-loaded nanobubbles (Dex@NBs-TRPC6)—an innovative therapeutic platform that enables selective podocyte delivery alongside real-time monitoring capabilities. Results The Dex@NBs-TRPC6 nanobubble system comprises polyethylene glycol-modified lipid vesicles encapsulating dexamethasone (Dex), conjugated with TRPC6-specific antibody for precise podocyte targeting delivery. Comprehensive in vivo and in vitro evaluations demonstrated the robust kidney and podocyte-targeting capabilities of Dex@NBs-TRPC6. Functional assays in mouse podocyte cells revealed that Dex@NBs-TRPC6 significantly outperformed free Dex and non-targeted nanobubbles (Dex@NBs) in mitigating cell apoptosis and inflammation. In an adriamycin-induced mouse nephropathy model, Dex@NBs-TRPC6, administered at half the dosage of free Dex, markedly alleviated proteinuria, glomerular and tubular damage, renal apoptosis, inflammation and fibrosis. Notably, Dex@NBs-TRPC6 attenuated the overexpression of hepatic gluconeogenic genes PCK1 and GCP6, a common adverse effect associated with Dex. Furthermore, leveraging the acoustic response properties of Dex@NBs-TRPC6, this delivery system integrates ultrasound imaging capabilities, enabling real-time visualization and therapeutic monitoring. Conclusions By simultaneously enhancing therapeutic efficacy, minimizing systemic toxicity, and enabling personalized imaging-guided treatment, Dex@NBs-TRPC6 introduces a transformative approach to GC-based renal therapy. |
| format | Article |
| id | doaj-art-c38b2ab63cc049ec9c2946eb9b3236c9 |
| institution | DOAJ |
| issn | 1477-3155 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj-art-c38b2ab63cc049ec9c2946eb9b3236c92025-08-20T03:16:32ZengBMCJournal of Nanobiotechnology1477-31552025-05-0123112110.1186/s12951-025-03487-8TRPC6-targeted dexamethasone nanobubbles with ultrasound-guided theranostics for adriamycin-induced nephropathyLin Wu0Yang Liu1Ziqi Fu2Honglei Guo3Kang Liu4Jiafa Ren5Zhimin Huang6Fang Yang7Huijuan Mao8Department of Nephrology, First Affiliated Hospital with Nanjing Medical University, Nanjing Medical UniversityState Key Laboratory of Digital Medical Engineering, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Sciences and Medical Engineering, Southeast UniversityDepartment of Nephrology, First Affiliated Hospital with Nanjing Medical University, Nanjing Medical UniversityDepartment of Nephrology, First Affiliated Hospital with Nanjing Medical University, Nanjing Medical UniversityDepartment of Nephrology, First Affiliated Hospital with Nanjing Medical University, Nanjing Medical UniversityDepartment of Nephrology, First Affiliated Hospital with Nanjing Medical University, Nanjing Medical UniversityDepartment of Nephrology, First Affiliated Hospital with Nanjing Medical University, Nanjing Medical UniversityState Key Laboratory of Digital Medical Engineering, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Sciences and Medical Engineering, Southeast UniversityDepartment of Nephrology, First Affiliated Hospital with Nanjing Medical University, Nanjing Medical UniversityAbstract Background Glucocorticoid (GC) intolerance and systemic toxicity pose significant challenges in the treatment of primary nephrotic syndrome (PNS), underscoring the urgent need for targeted therapies that maximize efficacy while minimizing adverse effects. To address these challenges, we developed TRPC6-targeted dexamethasone-loaded nanobubbles (Dex@NBs-TRPC6)—an innovative therapeutic platform that enables selective podocyte delivery alongside real-time monitoring capabilities. Results The Dex@NBs-TRPC6 nanobubble system comprises polyethylene glycol-modified lipid vesicles encapsulating dexamethasone (Dex), conjugated with TRPC6-specific antibody for precise podocyte targeting delivery. Comprehensive in vivo and in vitro evaluations demonstrated the robust kidney and podocyte-targeting capabilities of Dex@NBs-TRPC6. Functional assays in mouse podocyte cells revealed that Dex@NBs-TRPC6 significantly outperformed free Dex and non-targeted nanobubbles (Dex@NBs) in mitigating cell apoptosis and inflammation. In an adriamycin-induced mouse nephropathy model, Dex@NBs-TRPC6, administered at half the dosage of free Dex, markedly alleviated proteinuria, glomerular and tubular damage, renal apoptosis, inflammation and fibrosis. Notably, Dex@NBs-TRPC6 attenuated the overexpression of hepatic gluconeogenic genes PCK1 and GCP6, a common adverse effect associated with Dex. Furthermore, leveraging the acoustic response properties of Dex@NBs-TRPC6, this delivery system integrates ultrasound imaging capabilities, enabling real-time visualization and therapeutic monitoring. Conclusions By simultaneously enhancing therapeutic efficacy, minimizing systemic toxicity, and enabling personalized imaging-guided treatment, Dex@NBs-TRPC6 introduces a transformative approach to GC-based renal therapy.https://doi.org/10.1186/s12951-025-03487-8 |
| spellingShingle | Lin Wu Yang Liu Ziqi Fu Honglei Guo Kang Liu Jiafa Ren Zhimin Huang Fang Yang Huijuan Mao TRPC6-targeted dexamethasone nanobubbles with ultrasound-guided theranostics for adriamycin-induced nephropathy Journal of Nanobiotechnology |
| title | TRPC6-targeted dexamethasone nanobubbles with ultrasound-guided theranostics for adriamycin-induced nephropathy |
| title_full | TRPC6-targeted dexamethasone nanobubbles with ultrasound-guided theranostics for adriamycin-induced nephropathy |
| title_fullStr | TRPC6-targeted dexamethasone nanobubbles with ultrasound-guided theranostics for adriamycin-induced nephropathy |
| title_full_unstemmed | TRPC6-targeted dexamethasone nanobubbles with ultrasound-guided theranostics for adriamycin-induced nephropathy |
| title_short | TRPC6-targeted dexamethasone nanobubbles with ultrasound-guided theranostics for adriamycin-induced nephropathy |
| title_sort | trpc6 targeted dexamethasone nanobubbles with ultrasound guided theranostics for adriamycin induced nephropathy |
| url | https://doi.org/10.1186/s12951-025-03487-8 |
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