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Promoting Dual-Targeting Anticancer Effect by Regulating the Dynamic Intracellular Self-Assembly.

Shijin Zhang1, Ye Zhang1

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ACS Applied Materials & Interfaces
|August 22, 2020
PubMed
Summary

Researchers developed a novel nanodelivery system by functionalizing drug carriers with subcellular-targeting peptides. This approach enhances drug loading and achieves synergistic anticancer effects by simultaneous release of chemotherapy drugs and targeting excipients.

Keywords:
ER stressanticancerchlorambucildual-targetinginstructed self-assembly

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Area of Science:

  • Nanomedicine
  • Drug Delivery Systems
  • Cancer Therapeutics

Background:

  • Nanomedicine offers promise for complex diseases but faces high R&D costs.
  • Current nanotechnology applications focus on drug delivery to improve bioavailability and control.
  • Existing nanodelivery systems often lack multifunctional capabilities, limiting their therapeutic potential.

Purpose of the Study:

  • To develop a cost-effective nanodelivery system with enhanced functionality.
  • To engineer excipients with subcellular-targeting abilities to improve drug delivery.
  • To investigate the synergistic anticancer effects of simultaneously released targeted drugs and excipients.

Main Methods:

  • Covalent conjugation of fluorescent endoplasmic reticulum-targeted peptides to chlorambucil.
  • Development of a nanodelivery system utilizing these modified peptides.
  • In vitro assessment of drug-loading efficiency and intracellular release dynamics.
  • Visualization of enzyme-catalyzed hydrolysis and drug release within cells.

Main Results:

  • Achieved enhanced drug-loading efficiency of chlorambucil with ER-targeted peptides.
  • Demonstrated simultaneous release of nucleus-targeting chlorambucil and ER-targeting excipients via intracellular hydrolysis.
  • Observed synergistic anticancer effects attributed to the targeted and simultaneous drug release.
  • Elucidated the influence of intracellular self-assembly on enzymatic drug release.

Conclusions:

  • Functionalizing nanodelivery systems with subcellular-targeting excipients is a viable strategy to overcome cost barriers in nanomedicine.
  • Simultaneous release of targeted drugs and excipients can achieve synergistic therapeutic outcomes.
  • Intracellular self-assembly dynamics play a crucial role in enzyme-catalyzed drug release mechanisms.