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Related Experiment Video

Updated: Aug 27, 2025

Isolation of Labile Multi-protein Complexes by in vivo Controlled Cellular Cross-Linking and Immuno-magnetic Affinity Chromatography
10:50

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Robust Reversible Cross-Linking Strategy for Intracellular Protein Delivery with Excellent Serum Tolerance.

Song Zhang1, Echuan Tan1, Ruijue Wang1

  • 1South China Advanced Institute for Soft Matter Science and Technology, School of Emergent Soft Matter, Guangdong Provincial Key Laboratory of Functional and Intelligent Hybrid Materials and Devices, South China University of Technology, Guangzhou, 510640, China.

Nano Letters
|September 29, 2022
PubMed
Summary

This study introduces a novel reversible cross-linking strategy to enhance polymer stability for effective intracellular protein delivery. The method improves serum tolerance, enabling robust protein release within cells.

Keywords:
intracellular protein deliverynanoparticlespolymersreversible cross-linkingserum tolerance

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Area of Science:

  • Biomaterials Science
  • Nanotechnology
  • Drug Delivery

Background:

  • Intracellular protein delivery is crucial for biomedical applications.
  • Existing delivery systems suffer from poor serum stability due to protein adsorption.
  • This limits their efficacy in physiological conditions.

Purpose of the Study:

  • To develop a robust strategy for intracellular protein delivery with enhanced serum stability.
  • To improve the performance of cationic polymers in biological environments.
  • To create a versatile delivery system for various proteins and cell types.

Main Methods:

  • Assembling nanoparticles using cargo proteins and cationic polymers.
  • Stabilizing nanoparticles with a glutathione-cleavable and traceless cross-linker.
  • Evaluating nanoparticle stability, cell internalization, and protein release in serum-containing media.

Main Results:

  • The cross-linked nanoparticles demonstrated high stability in serum.
  • Efficient cell internalization and cargo protein release were observed.
  • The delivery system showed responsiveness to intracellular glutathione and acidic pH.
  • The strategy proved versatile across different polymers, proteins, and cell lines.

Conclusions:

  • A facile and efficient reversible cross-linking strategy enhances serum tolerance of cationic polymers.
  • This approach enables robust intracellular protein delivery.
  • The developed system offers a promising solution for overcoming serum-related challenges in protein delivery.