Theranostic nanoemulsions suppress macrophage-mediated acute inflammation in rats
Abstract In inflammatory diseases or following an injury, dysregulated inflammation is a common driver of pain and tissue damage. Macrophages are immune cells that contribute to the initiation, maintenance, and resolution of inflammation due to their phenotypic plasticity in response to signals from...
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| Format: | Article |
| Language: | English |
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BMC
2025-02-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-025-03164-w |
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| author | Riddhi Vichare Yalcin Kulahci Rebecca McCallin Fatih Zor Fatma Nurefsan Selek Lu Liu Caitlin Crelli Anneliese Troidle Michele Herneisey James M. Nichols Andrew J. Shepherd Vijay S. Gorantla Jelena M. Janjic |
| author_facet | Riddhi Vichare Yalcin Kulahci Rebecca McCallin Fatih Zor Fatma Nurefsan Selek Lu Liu Caitlin Crelli Anneliese Troidle Michele Herneisey James M. Nichols Andrew J. Shepherd Vijay S. Gorantla Jelena M. Janjic |
| author_sort | Riddhi Vichare |
| collection | DOAJ |
| description | Abstract In inflammatory diseases or following an injury, dysregulated inflammation is a common driver of pain and tissue damage. Macrophages are immune cells that contribute to the initiation, maintenance, and resolution of inflammation due to their phenotypic plasticity in response to signals from inflammatory microenvironments. Macrophages infiltrate and polarize toward a pro-inflammatory phenotype (M1-like), thereby increasing the severity of inflammation. Therefore, we aimed to suppress the pro-inflammatory activity of M1-like macrophages and decrease their infiltration at the site of inflammatory insult to resolve tissue inflammation. To achieve this, we developed a theranostic curcumin-loaded nanoemulsion platform that delivers a low dose of curcumin, a known anti-inflammatory phytochemical, to macrophages and allows in vivo tracking of macrophages by near-infrared fluorescence (NIRF) imaging technique. In vitro, we showed that curcumin-loaded nanoemulsion suppressed polarization of macrophages towards M1-like phenotype, consequently decreasing the release of pro-inflammatory cytokines and mediators like IL-6, IL- $$\:\beta\:,$$ TNF- $$\:\alpha\:$$ , and nitric oxide (NO). Furthermore, curcumin-loaded nanoemulsion increased the level of IL-10, an anti-inflammatory cytokine, and protected macrophages against ferroptosis compared to drug-free nanoemulsion. In a rodent model of Complete Freund’s adjuvant (CFA)-induced inflammation, we demonstrated that infiltrating macrophages sequestered curcumin-loaded nanoemulsion droplets and acted as cellular drug depots at the site of inflammation. This consequently decreased macrophage infiltration at the CFA-induced inflammation site in both sexes compared to drug-free nanoemulsion, as demonstrated by NIRF imaging, H&E staining, and immunofluorescence. Taken together, our results indicated that the anti-inflammatory efficacy of curcumin was significantly improved when directly delivered to pro-inflammatory macrophages via theranostic nanoemulsion. This work opens an avenue for exploring theranostic nanoemulsions as a platform for delivering natural anti-inflammatory products for immune modulation. Graphical abstract |
| format | Article |
| id | doaj-art-1e6b4ebad1a541239c792b695af173f1 |
| institution | Kabale University |
| issn | 1477-3155 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj-art-1e6b4ebad1a541239c792b695af173f12025-02-09T12:53:03ZengBMCJournal of Nanobiotechnology1477-31552025-02-0123112010.1186/s12951-025-03164-wTheranostic nanoemulsions suppress macrophage-mediated acute inflammation in ratsRiddhi Vichare0Yalcin Kulahci1Rebecca McCallin2Fatih Zor3Fatma Nurefsan Selek4Lu Liu5Caitlin Crelli6Anneliese Troidle7Michele Herneisey8James M. Nichols9Andrew J. Shepherd10Vijay S. Gorantla11Jelena M. Janjic12School of Pharmacy and Graduate School of Pharmaceutical Sciences, Duquesne UniversityDepartment of Surgery, Wake Forest University School of MedicineSchool of Pharmacy and Graduate School of Pharmaceutical Sciences, Duquesne UniversityDepartment of Surgery, Wake Forest University School of MedicineDepartment of Surgery, Wake Forest University School of MedicineSchool of Pharmacy and Graduate School of Pharmaceutical Sciences, Duquesne UniversitySchool of Pharmacy and Graduate School of Pharmaceutical Sciences, Duquesne UniversitySchool of Pharmacy and Graduate School of Pharmaceutical Sciences, Duquesne UniversitySchool of Pharmacy and Graduate School of Pharmaceutical Sciences, Duquesne UniversityDepartment of Symptom Research, Division of Internal Medicine, The University of Texas MD Anderson Cancer CenterDepartment of Symptom Research, Division of Internal Medicine, The University of Texas MD Anderson Cancer CenterDepartment of Surgery, Wake Forest University School of MedicineSchool of Pharmacy and Graduate School of Pharmaceutical Sciences, Duquesne UniversityAbstract In inflammatory diseases or following an injury, dysregulated inflammation is a common driver of pain and tissue damage. Macrophages are immune cells that contribute to the initiation, maintenance, and resolution of inflammation due to their phenotypic plasticity in response to signals from inflammatory microenvironments. Macrophages infiltrate and polarize toward a pro-inflammatory phenotype (M1-like), thereby increasing the severity of inflammation. Therefore, we aimed to suppress the pro-inflammatory activity of M1-like macrophages and decrease their infiltration at the site of inflammatory insult to resolve tissue inflammation. To achieve this, we developed a theranostic curcumin-loaded nanoemulsion platform that delivers a low dose of curcumin, a known anti-inflammatory phytochemical, to macrophages and allows in vivo tracking of macrophages by near-infrared fluorescence (NIRF) imaging technique. In vitro, we showed that curcumin-loaded nanoemulsion suppressed polarization of macrophages towards M1-like phenotype, consequently decreasing the release of pro-inflammatory cytokines and mediators like IL-6, IL- $$\:\beta\:,$$ TNF- $$\:\alpha\:$$ , and nitric oxide (NO). Furthermore, curcumin-loaded nanoemulsion increased the level of IL-10, an anti-inflammatory cytokine, and protected macrophages against ferroptosis compared to drug-free nanoemulsion. In a rodent model of Complete Freund’s adjuvant (CFA)-induced inflammation, we demonstrated that infiltrating macrophages sequestered curcumin-loaded nanoemulsion droplets and acted as cellular drug depots at the site of inflammation. This consequently decreased macrophage infiltration at the CFA-induced inflammation site in both sexes compared to drug-free nanoemulsion, as demonstrated by NIRF imaging, H&E staining, and immunofluorescence. Taken together, our results indicated that the anti-inflammatory efficacy of curcumin was significantly improved when directly delivered to pro-inflammatory macrophages via theranostic nanoemulsion. This work opens an avenue for exploring theranostic nanoemulsions as a platform for delivering natural anti-inflammatory products for immune modulation. Graphical abstracthttps://doi.org/10.1186/s12951-025-03164-wInflammationMacrophagesCurcuminNanoemulsionsTheranostic |
| spellingShingle | Riddhi Vichare Yalcin Kulahci Rebecca McCallin Fatih Zor Fatma Nurefsan Selek Lu Liu Caitlin Crelli Anneliese Troidle Michele Herneisey James M. Nichols Andrew J. Shepherd Vijay S. Gorantla Jelena M. Janjic Theranostic nanoemulsions suppress macrophage-mediated acute inflammation in rats Journal of Nanobiotechnology Inflammation Macrophages Curcumin Nanoemulsions Theranostic |
| title | Theranostic nanoemulsions suppress macrophage-mediated acute inflammation in rats |
| title_full | Theranostic nanoemulsions suppress macrophage-mediated acute inflammation in rats |
| title_fullStr | Theranostic nanoemulsions suppress macrophage-mediated acute inflammation in rats |
| title_full_unstemmed | Theranostic nanoemulsions suppress macrophage-mediated acute inflammation in rats |
| title_short | Theranostic nanoemulsions suppress macrophage-mediated acute inflammation in rats |
| title_sort | theranostic nanoemulsions suppress macrophage mediated acute inflammation in rats |
| topic | Inflammation Macrophages Curcumin Nanoemulsions Theranostic |
| url | https://doi.org/10.1186/s12951-025-03164-w |
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