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Boronate Building Blocks for Intracellular Protein Delivery
Qianyi Ren1, Yiyun Cheng1, Jia Lv1
1Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, 200241, China.
Advanced Healthcare Materials
|November 11, 2022
Summary
Boronate building blocks offer a versatile solution for intracellular protein delivery, overcoming challenges like cellular uptake and endosomal escape. These modifications enable targeted delivery and controlled release of therapeutic proteins within cells.
Area of Science:
- Biotechnology
- Materials Science
- Cell Biology
Background:
- Intracellular protein delivery is crucial for biotherapeutics but faces challenges such as protein binding, cellular uptake, endosomal escape, and release.
- Boronate building blocks are promising for overcoming these limitations due to their reactivity and stimuli-responsive nature.
Purpose of the Study:
- To explore the use of boronate building blocks for efficient intracellular protein delivery.
- To highlight the mechanisms by which boronates facilitate protein transport and release within cells.
Main Methods:
- Utilizing boronate ligands to form reversible bonds with cell surface carbohydrates (e.g., sialic acid) for receptor-mediated endocytosis.
- Modifying cargo proteins with boronates to enhance binding to nanocarriers.
- Investigating stimuli-responsive release of proteins within endolysosomes triggered by acidity, reactive oxygen species, or adenosine triphosphate.
- Decorating nanocarriers with boronate ligands for improved native protein binding via nitrogen-boron coordination.
Main Results:
- Boronate ligands facilitate protein entry into the cytosol via receptor-mediated endocytosis.
- Boronate modification enhances protein complexation with nanocarriers.
- Boronate-tagged proteins exhibit stimuli-responsive release within the cell, with potential nuclear transport.
- Boronate decoration on nanocarriers improves affinity for native proteins.
Conclusions:
- Boronate building blocks are highly effective for intracellular protein delivery systems.
- Their versatile reactivity and stimuli-responsive properties enable efficient cargo transport, release, and potential nuclear localization.
- Boronate-based supramolecular and dynamic nanoassemblies represent a promising strategy for advanced biotherapeutics.
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