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Evaluation of Polymeric Gene Delivery Nanoparticles by Nanoparticle Tracking Analysis and High-throughput Flow Cytometry

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Multifunctional degradable highly branched-linear poly(β-amino esters) for efficient YAP gene delivery.

Linjing Shi¹, Sen Luo¹, Zhuo Huang¹

¹Department of Dermatology, Department of Bone and Joint Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China.

Biomaterials Science

|February 25, 2026

Summary

Researchers developed a novel polymer, H-LPAE-1, for efficient Yes-associated protein (YAP) gene delivery in cancer cells. This breakthrough offers a promising strategy for cancer research and skin tissue repair applications.

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Area of Science:

Polymer Chemistry
Gene Therapy
Oncology

Background:

The Yes-associated protein (YAP) gene is crucial for cancer pathogenesis and skin tissue repair.
Developing safe and efficient YAP gene delivery systems is essential for clinical applications but remains challenging.

Purpose of the Study:

To synthesize novel highly branched-linear poly(β-amino esters) (H-LPAEs) for efficient YAP gene delivery.
To evaluate the transfection efficiency and safety profile of synthesized H-LPAEs in cancer cells.

Main Methods:

A two-step linear oligomer combination branching strategy was used to synthesize H-LPAEs.
Gene transfection efficiency was assessed using RT-PCR and western blot analyses.
Cytotoxicity assays were performed to evaluate the safety profile.

Main Results:

H-LPAE-1 demonstrated exceptional gene transfection efficiency, reaching up to 76.6% across various cell types.
The synthesized H-LPAEs effectively condensed DNA into nanosized polyplexes, facilitating cellular uptake.
H-LPAE-1 showed a superior safety profile and highly efficient YAP DNA delivery in cutaneous squamous cell carcinoma (SCC).

Conclusions:

The study presents a novel and easy-to-operate "oligomer combination branching strategy" for synthesizing H-LPAEs.
H-LPAE-1 is identified as a promising candidate for effective YAP gene delivery in cancer therapy and tissue regeneration.