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A sequentially responsive and structure-transformable nanoparticle with a comprehensively improved 'CAPIR cascade'

Chenfeng Xu1, Yu Sun, Yulin Yu

  • 1Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan 430030, China. zhipingzhang@mail.hust.edu.cn.

Nanoscale
|January 3, 2019
PubMed
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This study developed a smart nanoparticle system that improves drug delivery for cancer therapy by sequentially responding to tumor conditions. The enhanced nanoparticle system significantly boosts antitumor efficacy and extends survival rates.

Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Drug Delivery Systems

Background:

  • Intravenously administered drug delivery systems require efficient circulation, accumulation, penetration, internalization, and release (CAPIR) for optimal therapeutic outcomes.
  • Improving each step of the CAPIR cascade is crucial for enhancing treatment benefits and patient survival rates.

Purpose of the Study:

  • To develop a pH/matrix metalloproteinase-9 (MMP9) sequentially responsive nanoparticle system for enhanced cancer therapy.
  • To comprehensively improve the CAPIR cascade for superior therapeutic efficacy and survival rates.

Main Methods:

  • A doxorubicin (DOX)-conjugated peptide was used to assemble pH-responsive spherical nanoparticles (RGD-sNPs) at pH 7.4.
  • Utilized passive and active targeting for tumor accumulation, MMP9-triggered transformation into rod-like nanoparticles (S-NFs) for enhanced penetration and retention, and intracellular acidic pH for drug release.

Related Experiment Videos

  • Investigated nanoparticle transformation, tumor penetration, drug retention, cellular internalization, cytotoxicity, and in vivo antitumor efficacy.

    • Main Results:

    • RGD-sNPs demonstrated efficient tumor accumulation (∼15.1% ID g-1 at 24 h) and transformed into S-NFs in the tumor microenvironment.
    • S-NFs exhibited enhanced tumor penetration, prolonged drug retention (∼3.7% ID g-1 at 96 h), and a 2-fold increase in cellular internalization.
    • The system achieved rapid DOX release in weakly acidic intracellular conditions, leading to cytotoxicity and apoptosis, with remaining peptides forming cytotoxic fibers for synergistic antitumor effects.

    Conclusions:

    • The developed nanoparticle system effectively improves all stages of the CAPIR cascade, leading to enhanced antitumor efficacy.
    • This sequentially responsive and structure-transformable nanoparticle system offers a promising strategy for developing high-performance antitumor nanomedicines.
    • The RGD-sNPs significantly extended the median survival period to 55 days, demonstrating superior therapeutic potential.