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Related Experiment Video

Updated: Feb 4, 2026

Preparation of Neutrally-charged, pH-responsive Polymeric Nanoparticles for Cytosolic siRNA Delivery
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A modular assembly pH-sensitive charge reversal siRNA delivery system.

Qiong Sun1, Chunming Tang1, Zhigui Su1

  • 1State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Advanced Pharmaceuticals and Biomaterials, China Pharmaceutical University, Nanjing 210009, China. zhangcan@cpu.edu.cn.

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|October 11, 2018
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Summary

This study presents a novel pH-sensitive charge-reversal siRNA delivery system (PC) for cancer therapy. The PC system enhances tumor cellular uptake and therapeutic efficacy by reversing charge in acidic tumor environments.

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Area of Science:

  • Biotechnology
  • Nanomedicine
  • Molecular Therapy

Background:

  • Cationic lipids and polymers are common non-viral siRNA vectors but cause toxicity and aggregation.
  • Existing charge shielding strategies for siRNA delivery remain insufficient.
  • There is a need for safer and more effective siRNA delivery systems for cancer therapy.

Purpose of the Study:

  • To develop a facile modular assembly strategy for a pH-sensitive charge-reversal siRNA delivery system (PC).
  • To evaluate the PC system's ability to enhance tumor cellular uptake, intracellular siRNA release, and therapeutic efficacy.
  • To demonstrate the potential of this platform for cancer therapy.

Main Methods:

  • A modular assembly strategy was used to create pH-sensitive charge-reversal siRNA delivery systems (PC) by adjusting module ratios.
  • The PC system's charge properties at different pH values were characterized.
  • The PC system's ability to facilitate siRNA release and cellular uptake was assessed.
  • The therapeutic efficacy of PC loaded with survivin siRNA (cpusiRNA2) was evaluated in vitro and in vivo.

Main Results:

  • The developed PC system exhibits electronegativity at neutral pH and reverses to electropositive at acidic pH.
  • The PC system demonstrated enhanced tumor cellular uptake and efficient intracellular siRNA release.
  • cpusiRNA2 loaded in the PC system specifically down-regulated survivin expression.
  • Remarkable tumor therapeutic efficacy was observed in vitro and in vivo.

Conclusions:

  • The facile modular assembly strategy provides a promising platform for designing effective siRNA delivery systems.
  • The pH-sensitive charge-reversal PC system offers a potential solution for overcoming the limitations of current non-viral vectors.
  • This approach holds significant promise for advancing siRNA-based cancer therapy.