Interrogating the impact of aggregation‐induced emission nanoparticles on in vitro protein stability, ex vivo protein homeostasis, and in vivo biocompatibility
Abstract Aggregation‐induced emission (AIE) materials offer promising perspectives in disease diagnosis and therapeutics given their unique optical and photochemical properties. A key step toward translational applications for AIE materials is to systematically and vigorously evaluate their biosafet...
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| Format: | Article |
| Language: | English |
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Wiley
2022-12-01
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| Series: | Aggregate |
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| Online Access: | https://doi.org/10.1002/agt2.274 |
| _version_ | 1797976233093365760 |
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| author | Wang Wan Qun Zhao Biao Jing Congcong Peng Mengdie Wang Yanan Huang Wenhan Jin Bowen Zhong Zhenduo Zhang Xuepeng Dong Zhenming Gao Lihua Zhang Yu Liu |
| author_facet | Wang Wan Qun Zhao Biao Jing Congcong Peng Mengdie Wang Yanan Huang Wenhan Jin Bowen Zhong Zhenduo Zhang Xuepeng Dong Zhenming Gao Lihua Zhang Yu Liu |
| author_sort | Wang Wan |
| collection | DOAJ |
| description | Abstract Aggregation‐induced emission (AIE) materials offer promising perspectives in disease diagnosis and therapeutics given their unique optical and photochemical properties. A key step toward translational applications for AIE materials is to systematically and vigorously evaluate their biosafety and biocompatibility. While previous studies focus on cellular viability and toxicity, the impact of AIE materials on detailed stress responses manifesting cellular fitness has been less explored. Herein, this work provides the first piece of evidence to support amphiphilic functionalization of AIE nanoparticles minimizes the deterioration on proteome stability and cellular protein homeostasis (proteostasis). To this end, four scaffolds of AIE molecules were prepared, further functionalized into eight nanoparticles with two amphiphilic shells respectively, and characterized for their physicochemical properties. Thermal shift assay quantitatively demonstrates that AIE materials after amphiphilic functionalization into nanoparticles enhance proteome thermodynamic stability and ameliorate proteome aggregation propensity in cellular lysate, echoed by cell viability and fractionation experiments. Intriguingly, poor polydispersity index (PDI) of functionalized nanoparticles exaggerates their retention and aggregation in the cell. Comparative proteomic analysis uncovers that amphiphilic functionalization of AIE materials can minimize the deterioration of cellular protein homeostasis network. Finally, vigorous interrogation of functionalized AIE nanoparticles in mice model reveals the complexity of factors affecting the biocompatibility profiles in vivo, including materials’ size, PDI, and treatment frequencies. Overall, amphiphilic functionalization of AIE materials into nanoparticles is necessary to maintain proteome stability and balance cellular protein homeostasis. |
| first_indexed | 2024-04-11T04:47:50Z |
| format | Article |
| id | doaj.art-7527f9e9f4474583a2625b44ca3364bc |
| institution | Directory Open Access Journal |
| issn | 2692-4560 |
| language | English |
| last_indexed | 2024-04-11T04:47:50Z |
| publishDate | 2022-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Aggregate |
| spelling | doaj.art-7527f9e9f4474583a2625b44ca3364bc2022-12-27T06:37:38ZengWileyAggregate2692-45602022-12-0136n/an/a10.1002/agt2.274Interrogating the impact of aggregation‐induced emission nanoparticles on in vitro protein stability, ex vivo protein homeostasis, and in vivo biocompatibilityWang Wan0Qun Zhao1Biao Jing2Congcong Peng3Mengdie Wang4Yanan Huang5Wenhan Jin6Bowen Zhong7Zhenduo Zhang8Xuepeng Dong9Zhenming Gao10Lihua Zhang11Yu Liu12CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics Chinese Academy of Sciences Dalian ChinaCAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics Chinese Academy of Sciences Dalian ChinaCAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics Chinese Academy of Sciences Dalian ChinaCAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics Chinese Academy of Sciences Dalian ChinaCAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics Chinese Academy of Sciences Dalian ChinaCAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics Chinese Academy of Sciences Dalian ChinaCAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics Chinese Academy of Sciences Dalian ChinaCAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics Chinese Academy of Sciences Dalian ChinaCAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics Chinese Academy of Sciences Dalian ChinaThe Second Hospital of Dalian Medical University Dalian ChinaThe Second Hospital of Dalian Medical University Dalian ChinaCAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics Chinese Academy of Sciences Dalian ChinaCAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics Chinese Academy of Sciences Dalian ChinaAbstract Aggregation‐induced emission (AIE) materials offer promising perspectives in disease diagnosis and therapeutics given their unique optical and photochemical properties. A key step toward translational applications for AIE materials is to systematically and vigorously evaluate their biosafety and biocompatibility. While previous studies focus on cellular viability and toxicity, the impact of AIE materials on detailed stress responses manifesting cellular fitness has been less explored. Herein, this work provides the first piece of evidence to support amphiphilic functionalization of AIE nanoparticles minimizes the deterioration on proteome stability and cellular protein homeostasis (proteostasis). To this end, four scaffolds of AIE molecules were prepared, further functionalized into eight nanoparticles with two amphiphilic shells respectively, and characterized for their physicochemical properties. Thermal shift assay quantitatively demonstrates that AIE materials after amphiphilic functionalization into nanoparticles enhance proteome thermodynamic stability and ameliorate proteome aggregation propensity in cellular lysate, echoed by cell viability and fractionation experiments. Intriguingly, poor polydispersity index (PDI) of functionalized nanoparticles exaggerates their retention and aggregation in the cell. Comparative proteomic analysis uncovers that amphiphilic functionalization of AIE materials can minimize the deterioration of cellular protein homeostasis network. Finally, vigorous interrogation of functionalized AIE nanoparticles in mice model reveals the complexity of factors affecting the biocompatibility profiles in vivo, including materials’ size, PDI, and treatment frequencies. Overall, amphiphilic functionalization of AIE materials into nanoparticles is necessary to maintain proteome stability and balance cellular protein homeostasis.https://doi.org/10.1002/agt2.274aggregation‐induced emissionbiocompatibilitynanoparticlesprotein stabilityproteostasis |
| spellingShingle | Wang Wan Qun Zhao Biao Jing Congcong Peng Mengdie Wang Yanan Huang Wenhan Jin Bowen Zhong Zhenduo Zhang Xuepeng Dong Zhenming Gao Lihua Zhang Yu Liu Interrogating the impact of aggregation‐induced emission nanoparticles on in vitro protein stability, ex vivo protein homeostasis, and in vivo biocompatibility Aggregate aggregation‐induced emission biocompatibility nanoparticles protein stability proteostasis |
| title | Interrogating the impact of aggregation‐induced emission nanoparticles on in vitro protein stability, ex vivo protein homeostasis, and in vivo biocompatibility |
| title_full | Interrogating the impact of aggregation‐induced emission nanoparticles on in vitro protein stability, ex vivo protein homeostasis, and in vivo biocompatibility |
| title_fullStr | Interrogating the impact of aggregation‐induced emission nanoparticles on in vitro protein stability, ex vivo protein homeostasis, and in vivo biocompatibility |
| title_full_unstemmed | Interrogating the impact of aggregation‐induced emission nanoparticles on in vitro protein stability, ex vivo protein homeostasis, and in vivo biocompatibility |
| title_short | Interrogating the impact of aggregation‐induced emission nanoparticles on in vitro protein stability, ex vivo protein homeostasis, and in vivo biocompatibility |
| title_sort | interrogating the impact of aggregation induced emission nanoparticles on in vitro protein stability ex vivo protein homeostasis and in vivo biocompatibility |
| topic | aggregation‐induced emission biocompatibility nanoparticles protein stability proteostasis |
| url | https://doi.org/10.1002/agt2.274 |
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