Enzyme functionalized PEOz modified magnetic polydopamine with enhanced penetration for cascade-augmented synergistic

Siyuan Hao1, Jingjie Zuo1, Haowu Huang1

  • 1Key Laboratory of Fermentation Engineering (Ministry of Education), Key Laboratory of Industrial Microbiology in Hubei, National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Cooperative Innovation Center of Industrial Fermentation (Ministry of Education & Hubei Province), School of Bioengineering and Food, Hubei University of Technology, Wuhan 430068, China.

Insights

This study introduces novel nanoparticles (FDPGP) for enhanced cancer therapy. These nanoparticles combine multiple treatments, improving tumor penetration and achieving superior anticancer effects with good biosafety.

Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Oncology

Background:

  • Reactive oxygen species (ROS)-mediated cancer therapies offer high selectivity and safety.
  • Traditional therapies face challenges in tumor microenvironment penetration and multimodal ablation, limiting efficacy.
  • Developing advanced nanoplatforms is crucial for overcoming these limitations in cancer treatment.

Purpose of the Study:

  • To construct a multifunctional nanoparticle system (FDPGP) for enhanced tumor ablation.
  • To investigate the synergistic effects of photothermal therapy (PTT), starvation therapy (ST), chemodynamic therapy (CDT), and chemotherapy (CT).
  • To evaluate the in vitro and in vivo performance of the FDPGP nanoplatform for breast cancer treatment.

Main Methods:

  • Fabrication of magnetic polydopamine nanoparticles dual-loaded with doxorubicin (DOX) and glucose oxidase (GOx), decorated with poly (2-ethyl-2-oxazoline) (PEOz).
  • In vitro evaluation of pH-responsive charge reversal, drug release, photothermal properties, and cascade reactions.
  • In vitro and in vivo assessment of cellular uptake, cytotoxicity, tumor penetration, therapeutic efficacy, and biosafety.

Main Results:

  • FDPGP nanoparticles demonstrated pH-responsive charge reversal, controlled drug release, and effective photothermal conversion.
  • GOx-mediated cascade reactions amplified oxidative stress, synergistically inhibiting breast cancer cells.
  • In vivo studies showed excellent tumor enrichment, penetration, superior anticancer efficacy, and good biosafety through multimodal therapy.

Conclusions:

  • The FDPGP nanoplatform effectively integrates PTT, ST, CDT, and CT for enhanced tumor ablation.
  • This multimodal approach significantly improves therapeutic outcomes and biosafety in preclinical cancer models.
  • The FDPGP system offers a promising strategy for developing advanced, collaboratively enhanced tumor therapies.

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