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Related Experiment Video

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A Modular Platform for Enhanced Drug Delivery to Glioblastoma Using Targeted Multidomain Protein Assemblies.

Andrew L Wang1,2, Aparajita Bhattacharya1,2, Frances Lee1

  • 1Department of Chemical and Biomolecular Engineering, New York University Tandon School of Engineering, 6 MetroTech Center, Brooklyn, NY, 11201, USA.

Angewandte Chemie (International Ed. in English)
|July 3, 2025
PubMed
Summary

Researchers engineered protein nanocarriers to improve hydrophobic drug delivery for glioblastoma multiforme (GBM) treatment. The enhanced targeted multidomain protein assembly (TMPA) showed increased drug loading and cellular uptake, demonstrating potential for GBM therapy.

Keywords:
CancerDrug deliveryMicellesProtein engineeringSelf‐assembly

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Area of Science:

  • Biotechnology
  • Nanomedicine
  • Oncology

Background:

  • Protein-based nanocarriers offer biodegradability and biological barrier penetration.
  • Targeted delivery of hydrophobic drugs is crucial for treating glioblastoma multiforme (GBM).

Purpose of the Study:

  • To engineer protein nanocarriers for improved hydrophobic drug delivery in GBM treatment.
  • To enhance the efficacy of targeted multidomain protein assembly (TMPA) through modular protein engineering.

Main Methods:

  • Iterative protein engineering to modify coiled-coil and RGD peptide regions.
  • Assessing hydrodynamic size, drug loading capacity (doxorubicin), and cellular uptake (U87 GBM cells).
  • In vivo pharmacokinetic analysis and ex vivo fluorescence imaging in GBM-bearing mice.

Main Results:

  • Increased multiplicity (m) of targeting regions enhanced TMPA's micellar size and drug loading (1.7-fold increase in doxorubicin encapsulation).
  • TMPA demonstrated a 1.3-fold improvement in U87 human GBM cell uptake.
  • In vivo studies showed prolonged distribution-phase half-life and preferential tumor localization of NIR-TMPA in GBM-bearing mice.

Conclusions:

  • Modular protein engineering effectively improved TMPA's properties for GBM therapy.
  • TMPA exhibits enhanced drug delivery and tumor accumulation, highlighting its therapeutic potential.
  • Further development of TMPA derivatives could advance targeted GBM treatment strategies.