Dual-targeting nanotherapeutics antagonize hyperinsulinemia-promoted tumor growth via activating cell autophagy

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Jiarun Huang1, Yuedan Liu1, Ting Liu1

  • 1The First Affiliated Hospital, and Department of Chemistry, Jinan University, Guangzhou 510632, China. tchentf@jnu.edu.cn.

Journal of Materials Chemistry. B
|October 9, 2019
PubMed

Insights

This study introduces dual-targeting selenium nanoparticles (u/A-SeNPs) to combat tumors in type 2 diabetes. These nanoparticles promote autophagy and ROS production, leading to cancer cell apoptosis and antagonizing hyperinsulinemia.

Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Cancer Research

Background:

  • Hyperinsulinemia in type 2 diabetes mellitus (T2DM) fuels tumor growth by suppressing autophagy.
  • Developing effective antitumor agents that counteract hyperinsulinemia by enhancing autophagy is crucial.

Purpose of the Study:

  • To develop dual-targeting modified selenium nanoparticles (u/A-SeNPs) as a biocompatible chemotherapeutic agent.
  • To investigate the efficacy of u/A-SeNPs in antagonizing hyperinsulinemia and inhibiting tumor progression.

Main Methods:

  • u/A-SeNPs were synthesized by modifying selenium nanoparticles with chitosan (CS) and grafting targeted peptides (uPA/ACPP).
  • The cellular uptake mechanism, reactive oxygen species (ROS) generation, and autophagy levels were analyzed.
  • Mitochondrial fragmentation and apoptosis induction were assessed using monodansylcadaverine (MDC) and mRFP-GFP-LC3 assays.

Main Results:

  • u/A-SeNPs demonstrated enhanced selectivity and antitumor activity.
  • The nanoparticles were effectively internalized into tumor cells via receptor-mediated endocytosis, leading to excessive ROS production.
  • u/A-SeNPs significantly upregulated autophagy levels and induced mitochondrial fragmentation, triggering apoptosis.

Conclusions:

  • A feasible method for synthesizing dual-targeting nanomedicines was established.
  • Se-based nanotherapeutics offer a novel strategy for tumor therapy in the context of hyperinsulinemia.

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