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Updated: Feb 14, 2026

Using Scaffold Liposomes to Reconstitute Lipid-proximal Protein-protein Interactions In Vitro
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Lipid Modified with Pyridinium Betaine Manipulates Liposomal Membrane Fusion Behavior for Spatially Confined

Huijuan Zheng1, Chunxiong Zheng1, Yongkang Du1

  • 1School of Chemistry, South China Normal University, Guangzhou, 510006, China.

Angewandte Chemie (International Ed. in English)
|February 13, 2026
PubMed

Insights

Researchers developed pH-responsive liposomes (SENDFUL) that precisely control membrane fusion in tumors. This targeted delivery enhances therapeutic efficacy and reduces systemic toxicity by confining fusion to acidic tumor environments.

Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Drug Delivery

Background:

  • Fusogenic delivery systems enhance cancer therapy but lack precise control, causing toxicity.
  • Current fusion-regulating strategies are often insensitive and unidirectional, limiting efficacy and safety.

Purpose of the Study:

  • To design a pH-responsive regulator for precise control of liposomal membrane fusion.
  • To develop a self-adaptive, environment-responsive fusogenic liposome (SENDFUL) for tumor-specific delivery.

Main Methods:

  • Synthesized a pyridinium betaine-capped lipid (DSPCPA) as a pH-responsive regulator.
  • Formulated SENDFUL liposomes incorporating DSPCPA for tunable membrane fusion.
  • Constructed a STING pathway nanoagonist using SENDFUL for in vitro and in vivo studies.

Main Results:

  • SENDFUL exhibits reversible pH-dependent charge switching, enabling fusogenic activity in acidic tumor microenvironments.
  • Protonation of DSPCPA at pH 6.5 triggers tumor-specific membrane fusion and lysosome-bypassing cytosolic delivery.
  • SENDFUL-based STING agonist demonstrated potent antitumor immunity with minimal toxicity.

Conclusions:

  • SENDFUL provides precise spatial regulation of liposomal membrane fusion.
  • This technology offers a safe and efficient platform for tumor-specific intracellular drug delivery.
  • SENDFUL advances cancer therapy by enhancing drug delivery and reducing systemic side effects.
Keywords:
Biomaterialcancer therapycytoplasmic deliverymembrane fusionnanocarrier

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