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Updated: Aug 5, 2025

Cell Squeezing as a Robust, Microfluidic Intracellular Delivery Platform

Cell Squeezing as a Robust, Microfluidic Intracellular Delivery Platform

Published on: November 7, 2013

Mechanism-Driven Technology Development for Solving the Intracellular Delivery Problem of Hard-To-Transfect Cells.

Wanchuan Ding¹, Xuan Yang^2,3,4, Huoyue Lin¹

¹Department of Biomedical Engineering, College of Engineering and Applied Sciences, Nanjing University, Nanjing 210093, China.

|March 27, 2023

Summary

This summary is machine-generated.

Researchers found a new way to deliver molecules into difficult-to-transfect bone-marrow-derived mesenchymal stem cells (BMSCs). Coating nanoparticles with poly(disulfide) (PDS1) overcomes vesicle trapping, enhancing gene delivery and cell differentiation.

Keywords:

gene delivery nanomedicine quantum dot regenerative medicine stem cell tissue engineering transfection

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Last Updated: Aug 5, 2025

Cell Squeezing as a Robust, Microfluidic Intracellular Delivery Platform

Cell Squeezing as a Robust, Microfluidic Intracellular Delivery Platform

Published on: November 7, 2013

Direct Protein Delivery to Mammalian Cells Using Cell-permeable Cys2-His2 Zinc-finger Domains

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Published on: March 25, 2015

Engineering Cell-permeable Protein

Engineering Cell-permeable Protein

Published on: December 28, 2009

Area of Science:

Biotechnology
Cell Biology
Materials Science

Background:

Hard-to-transfect cells pose significant challenges for intracellular delivery, with limited understanding of underlying mechanisms.
Vesicle trapping has been identified as a key bottleneck for delivery into bone-marrow-derived mesenchymal stem cells (BMSCs).

Purpose of the Study:

To investigate methods for reducing vesicle trapping in BMSCs.
To develop effective nanoparticle-based delivery systems for BMSCs.
To explore the molecular basis for the difficulty in transfecting BMSCs.

Main Methods:

Screening of various vesicle trapping-reducing methods on BMSCs and HeLa cells.
Development and application of poly(disulfide) (PDS1)-coated nanoparticles for intracellular delivery.
Assessment of transfection efficiency for fluorescent protein plasmids and osteoblastic differentiation in BMSCs.
Mechanistic studies investigating the role of plasma membrane cholesterol content.

Main Results:

Most tested methods failed to reduce vesicle trapping in BMSCs, unlike in HeLa cells.
PDS1-coated nanoparticles effectively circumvented vesicle trapping in BMSCs via direct cell membrane penetration.
PDS1 nanoparticles significantly enhanced plasmid transfection and osteoblastic differentiation in BMSCs.
Higher cholesterol content in BMSC plasma membranes was implicated as a factor in impaired vesicle escape.

Conclusions:

Poly(disulfide) (PDS1) coating represents a breakthrough for overcoming vesicle trapping in hard-to-transfect BMSCs.
PDS1-coated nanoparticles offer a promising strategy for gene delivery and therapeutic applications in BMSCs.
Plasma membrane cholesterol levels may be a critical determinant of cellular barriers to nanoparticle delivery.