Staudinger Reaction-Responsive Coacervates for Cytosolic Antibody Delivery and TRIM21-Mediated Protein Degradation Article Swipe
Yishu Bao
,
Zhiyi Xu
,
Kai Cheng
,
Xiaojing Li
,
Fangke Chen
,
Dingdong Yuan
,
Fang Zhang
,
Audrey Run-Yu
,
Xiangze Zeng
,
Yuan‐Di Zhao
,
Jiang Xia
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1021/jacs.4c17054
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1021/jacs.4c17054
A low-molecular-weight compound whose structure strikes a fine balance between hydrophobicity and hydrophilicity may form coacervates via liquid-liquid phase separation in an aqueous solution. These coacervates may encapsulate and convoy proteins across the plasma membrane into the cell. However, releasing the cargo from the vehicle to the cytosol is challenging. Here, we address this issue by designing phase-separating coacervates, which are disassembled by the bioorthogonal Staudinger reaction. We constructed and selected triphenylphosphine-based compounds that formed phase-separated coacervates in an aqueous solution. Reacting the coacervates with azides resulted in microdroplet dissolution, so they received the name Staudinger Reaction-Responsive Coacervates, SR-Coa. SR-Coa could encapsulate proteins, including antibodies, and translocate them across the plasma membrane into the cell. Further treatment of the cell with ethyl azidoacetate induced the cargo dispersion from the puncta to the cytosolic distribution. We showcased an application of the SR-Coa/ethyl azidoacetate system in facilitating the translocation of the EGFR/antibody complex into the cell, which induced EGFR degradation via the TRIM21-dependent pathway both in vitro and in vivo. Besides the membrane protein EGFR, this system could also degrade endogenous protein EZH2. Taken together, here we report a strategy of controlling molecular coacervates by a bioorthogonal reaction in the cell for cytosolic protein delivery and demonstrate its use in promoting targeted protein degradation via the proteasome-dependent pathway.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1021/jacs.4c17054
- OA Status
- hybrid
- Cited By
- 5
- References
- 63
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4406319414
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4406319414Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1021/jacs.4c17054Digital Object Identifier
- Title
-
Staudinger Reaction-Responsive Coacervates for Cytosolic Antibody Delivery and TRIM21-Mediated Protein DegradationWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
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2025Year of publication
- Publication date
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2025-01-13Full publication date if available
- Authors
-
Yishu Bao, Zhiyi Xu, Kai Cheng, Xiaojing Li, Fangke Chen, Dingdong Yuan, Fang Zhang, Audrey Run-Yu, Xiangze Zeng, Yuan‐Di Zhao, Jiang XiaList of authors in order
- Landing page
-
https://doi.org/10.1021/jacs.4c17054Publisher landing page
- Open access
-
YesWhether a free full text is available
- OA status
-
hybridOpen access status per OpenAlex
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https://doi.org/10.1021/jacs.4c17054Direct OA link when available
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Coacervate, Chemistry, Cytosol, Bioorthogonal chemistry, Membrane, Biophysics, Biochemistry, Combinatorial chemistry, Click chemistry, Enzyme, BiologyTop concepts (fields/topics) attached by OpenAlex
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5Total citation count in OpenAlex
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2025: 5Per-year citation counts (last 5 years)
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63Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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| referenced_works | https://openalex.org/W4280616471, https://openalex.org/W4205379795, https://openalex.org/W4312064763, https://openalex.org/W2974568688, https://openalex.org/W4388479805, https://openalex.org/W4388892208, https://openalex.org/W3017485915, https://openalex.org/W3045619116, https://openalex.org/W3120553915, https://openalex.org/W3136546688, https://openalex.org/W4296691508, https://openalex.org/W4402827313, https://openalex.org/W4399861933, https://openalex.org/W3172027657, https://openalex.org/W4392756096, https://openalex.org/W3195114088, https://openalex.org/W4385945646, https://openalex.org/W2769995426, https://openalex.org/W2774294088, https://openalex.org/W4399843146, https://openalex.org/W4200463801, https://openalex.org/W4386809661, https://openalex.org/W4293780525, https://openalex.org/W4391338569, https://openalex.org/W2980403657, https://openalex.org/W3175628958, https://openalex.org/W2793266847, https://openalex.org/W1995961820, https://openalex.org/W2885614068, https://openalex.org/W3153006541, https://openalex.org/W2327059830, https://openalex.org/W2618923743, https://openalex.org/W4210968794, https://openalex.org/W2019407979, https://openalex.org/W4287837103, https://openalex.org/W4226034681, https://openalex.org/W2982671040, https://openalex.org/W3101342963, https://openalex.org/W3168096544, https://openalex.org/W4220848114, https://openalex.org/W4385851144, https://openalex.org/W4404588802, https://openalex.org/W4386305232, https://openalex.org/W2006192357, https://openalex.org/W2041568570, https://openalex.org/W4256503849, https://openalex.org/W2002916661, https://openalex.org/W1978407833, https://openalex.org/W2088497317, https://openalex.org/W2286017331, https://openalex.org/W2592928047, https://openalex.org/W1971698744, https://openalex.org/W1263616324, https://openalex.org/W2001216208, https://openalex.org/W4310277275, https://openalex.org/W2039595390, https://openalex.org/W2002616862, https://openalex.org/W3129289758, https://openalex.org/W4402030050, https://openalex.org/W4225124642, https://openalex.org/W2022754521, https://openalex.org/W2052172534, https://openalex.org/W2177603935 |
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