Two‐Pronged Attack: Dual Activation of Fat Reduction Using Near‐Infrared‐Responsive Nanosandwich for Targeted Anti‐Obesity Treatment
Abstract Excessive fat accumulation and chronic inflammation are two typical characteristics of obesity. AMP‐activated protein kinase (AMPK), a master regulator of energy metabolism, is involved in adipogenesis, lipogenesis, and inflammation modulation in adipose tissue (AT). Thus, effective lipid r...
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| Format: | Article |
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Wiley
2024-11-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202406985 |
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| author | Qiaqia Xiao Lu Tang Siying Chen Yijun Mei Chuying Wang Jing Yang Jing Shang Shengliang Li Wei Wang |
| author_facet | Qiaqia Xiao Lu Tang Siying Chen Yijun Mei Chuying Wang Jing Yang Jing Shang Shengliang Li Wei Wang |
| author_sort | Qiaqia Xiao |
| collection | DOAJ |
| description | Abstract Excessive fat accumulation and chronic inflammation are two typical characteristics of obesity. AMP‐activated protein kinase (AMPK), a master regulator of energy metabolism, is involved in adipogenesis, lipogenesis, and inflammation modulation in adipose tissue (AT). Thus, effective lipid reduction and anti‐inflammation through AMPK regulation play vital roles in treating obesity. Herein, an anti‐obesity nanosandwich is fabricated through attaching polymetformin (PolyMet) onto photothermal agent black phosphorus nanosheets (BP). PolyMet activates AMPK to inhibit adipogenesis, promote browning, and mitigate AT inflammation by decreasing macrophage infiltration, repolarizing macrophage phenotype, and downregulating pro‐inflammatory cytokines. Additionally, BP induces lipolysis and apoptosis of adipocytes and macrophages through a photothermal effect. By further functionalization using hyaluronic acid (HA) and MMP2 substrate‐linking P3 peptide‐modified HA (P3‐HA), an enhanced anti‐obesity effect is obtained by dual‐targeting of P3 and HA, and HA‐mediated CD44 poly‐clustering after MMP2 cleavage. Upon laser irradiation, the designed nanosandwich (P3‐HA/PM@BP) effectively inhibits obesity development in obese mice, increases M2/M1 ratio in AT, reduces the serum levels of cholesterol/triglyceride and improves insulin sensitivity, exhibiting promising research potential to facilitate the clinical development of modern anti‐obesity therapies. |
| format | Article |
| id | doaj-art-1fde09a6cde4424b8fbc92f661f21808 |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-1fde09a6cde4424b8fbc92f661f218082024-11-20T19:25:40ZengWileyAdvanced Science2198-38442024-11-011143n/an/a10.1002/advs.202406985Two‐Pronged Attack: Dual Activation of Fat Reduction Using Near‐Infrared‐Responsive Nanosandwich for Targeted Anti‐Obesity TreatmentQiaqia Xiao0Lu Tang1Siying Chen2Yijun Mei3Chuying Wang4Jing Yang5Jing Shang6Shengliang Li7Wei Wang8State Key Laboratory of Natural Medicines School of Pharmacy China Pharmaceutical University Nanjing 211198 P. R. ChinaState Key Laboratory of Natural Medicines School of Pharmacy China Pharmaceutical University Nanjing 211198 P. R. ChinaState Key Laboratory of Natural Medicines School of Pharmacy China Pharmaceutical University Nanjing 211198 P. R. ChinaState Key Laboratory of Natural Medicines School of Pharmacy China Pharmaceutical University Nanjing 211198 P. R. ChinaState Key Laboratory of Natural Medicines School of Pharmacy China Pharmaceutical University Nanjing 211198 P. R. ChinaState Key Laboratory of Natural Medicines School of Pharmacy China Pharmaceutical University Nanjing 211198 P. R. ChinaNMPA Key Laboratory for Research and Evaluation of Cosmetics China Pharmaceutical University Nanjing 211198 P. R. ChinaCollege of Pharmaceutical Sciences Soochow University Suzhou 215123 P. R. ChinaState Key Laboratory of Natural Medicines School of Pharmacy China Pharmaceutical University Nanjing 211198 P. R. ChinaAbstract Excessive fat accumulation and chronic inflammation are two typical characteristics of obesity. AMP‐activated protein kinase (AMPK), a master regulator of energy metabolism, is involved in adipogenesis, lipogenesis, and inflammation modulation in adipose tissue (AT). Thus, effective lipid reduction and anti‐inflammation through AMPK regulation play vital roles in treating obesity. Herein, an anti‐obesity nanosandwich is fabricated through attaching polymetformin (PolyMet) onto photothermal agent black phosphorus nanosheets (BP). PolyMet activates AMPK to inhibit adipogenesis, promote browning, and mitigate AT inflammation by decreasing macrophage infiltration, repolarizing macrophage phenotype, and downregulating pro‐inflammatory cytokines. Additionally, BP induces lipolysis and apoptosis of adipocytes and macrophages through a photothermal effect. By further functionalization using hyaluronic acid (HA) and MMP2 substrate‐linking P3 peptide‐modified HA (P3‐HA), an enhanced anti‐obesity effect is obtained by dual‐targeting of P3 and HA, and HA‐mediated CD44 poly‐clustering after MMP2 cleavage. Upon laser irradiation, the designed nanosandwich (P3‐HA/PM@BP) effectively inhibits obesity development in obese mice, increases M2/M1 ratio in AT, reduces the serum levels of cholesterol/triglyceride and improves insulin sensitivity, exhibiting promising research potential to facilitate the clinical development of modern anti‐obesity therapies.https://doi.org/10.1002/advs.202406985anti‐inflammationblack phosphorus nanosheetlipid reductionnanomedicineobesity |
| spellingShingle | Qiaqia Xiao Lu Tang Siying Chen Yijun Mei Chuying Wang Jing Yang Jing Shang Shengliang Li Wei Wang Two‐Pronged Attack: Dual Activation of Fat Reduction Using Near‐Infrared‐Responsive Nanosandwich for Targeted Anti‐Obesity Treatment Advanced Science anti‐inflammation black phosphorus nanosheet lipid reduction nanomedicine obesity |
| title | Two‐Pronged Attack: Dual Activation of Fat Reduction Using Near‐Infrared‐Responsive Nanosandwich for Targeted Anti‐Obesity Treatment |
| title_full | Two‐Pronged Attack: Dual Activation of Fat Reduction Using Near‐Infrared‐Responsive Nanosandwich for Targeted Anti‐Obesity Treatment |
| title_fullStr | Two‐Pronged Attack: Dual Activation of Fat Reduction Using Near‐Infrared‐Responsive Nanosandwich for Targeted Anti‐Obesity Treatment |
| title_full_unstemmed | Two‐Pronged Attack: Dual Activation of Fat Reduction Using Near‐Infrared‐Responsive Nanosandwich for Targeted Anti‐Obesity Treatment |
| title_short | Two‐Pronged Attack: Dual Activation of Fat Reduction Using Near‐Infrared‐Responsive Nanosandwich for Targeted Anti‐Obesity Treatment |
| title_sort | two pronged attack dual activation of fat reduction using near infrared responsive nanosandwich for targeted anti obesity treatment |
| topic | anti‐inflammation black phosphorus nanosheet lipid reduction nanomedicine obesity |
| url | https://doi.org/10.1002/advs.202406985 |
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