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Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?
Published on: June 13, 2014
Bimodal tumor-targeting from microenvironment responsive hyaluronan layer-by-layer (LbL) nanoparticles.
Erik C Dreaden1, Stephen W Morton, Kevin E Shopsowitz
1Koch Institute for Integrative Cancer Research, ‡Department of Chemical Engineering, and §Institute for Soldier Nanotechnologies, Massachusetts Institute of Technology , 500 Main Street, Cambridge, Massachusetts 02142, United States.
This study introduces a novel polymer drug carrier that targets tumors using pH-responsive and CD44 receptor-targeting strategies. This dual-action approach enhances tumor penetration and cellular uptake for improved cancer diagnostics and therapy.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Cellular heterogeneity in tumors presents a challenge for targeted drug delivery.
- Nanoscale drug carriers require effective strategies for tumor-specific delivery.
Purpose of the Study:
- To develop a tumor microenvironment-responsive nanoscale drug carrier with dual targeting mechanisms.
- To investigate the efficacy of pH-dependent and CD44 receptor-directed targeting for cancer therapy.
Main Methods:
- Fabrication of layer-by-layer (LbL) polymer nanoparticles using polyamine and hyaluronan.
- Evaluation of nanoparticle structural reorganization in response to hypoxic tumor pH.
- In vitro and in vivo assessment of nanoparticle cellular uptake, tumor penetration, and CD44 receptor binding.
Main Results:
- Hypoxic pH induced structural reorganization of hyaluronan-LbL nanoparticles.
- Nanoparticles demonstrated targeted cellular delivery, effective tumor penetration, and uptake in vitro and in vivo.
- Nanoscale drug carriers selectively bound CD44, diminished cancer cell migration, and co-localized with CD44 receptors in vivo.
Conclusions:
- Multimodal targeting using LbL nanoparticles is a potent strategy for tumor-specific cancer diagnostics and therapy.
- A single bilayer of polyamine and hyaluronan creates a dynamic interface for responsive nanoparticle function.

