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Endosomal pH-Responsive Fe-Based Hyaluronate Nanoparticles for Doxorubicin Delivery
Yangmun Bae1, Yoonyoung Kim1, Eun Seong Lee1,2
1Department of Biotechnology, The Catholic University of Korea, 43 Jibong-ro, Bucheon-si 14662, Gyeonggi-do, Korea.
Molecules (Basel, Switzerland)
|July 2, 2021
Summary
New pH-responsive nanoparticles loaded with chemotherapy drugs show improved tumor uptake and targeted drug release. These metal-based biopolymer nanoparticles offer a promising approach for enhanced cancer treatment strategies.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Drug Delivery Systems
Background:
- Targeted chemotherapy delivery remains a challenge in cancer treatment.
- Developing stimuli-responsive drug carriers can enhance therapeutic efficacy.
- Hyaluronic acid (HA) is a biopolymer that can target CD44 receptors overexpressed on tumor cells.
Purpose of the Study:
- To develop pH-responsive, metal-based biopolymer nanoparticles for tumor-specific chemotherapy.
- To investigate the potential of aminated hyaluronic acid (aHA) coupled with 2,3-dimethylmaleic anhydride (DMA) for creating drug-loaded nanoparticles.
- To evaluate the tumor cellular uptake and drug release characteristics of these nanoparticles.
Main Methods:
- Fabrication of doxorubicin (DOX)-loaded Fe-based hyaluronate nanoparticles (DOX@aHA-DMA/Fe NPs) via electrostatic complexation.
- Utilizing aminated hyaluronic acid (aHA) and 2,3-dimethylmaleic anhydride (DMA) as pH-responsive components.
- Assessing nanoparticle uptake in MDA-MB-231 cells (overexpressing CD44) using fluorescence intensity measurements.
- Investigating nanoparticle destabilization and drug release in an acidic environment.
Main Results:
- DOX@aHA-DMA/Fe NPs demonstrated enhanced cellular uptake in CD44-positive cancer cells compared to controls.
- Nanoparticle fluorescence intensity increased with higher DMA content (e.g., DOX@aHA-DMA0.60/Fe NPs showed ~9.3 × 10^2).
- The nanoparticles destabilized in acidic conditions, leading to accelerated doxorubicin release.
- The pH-responsive nature of the nanoparticles facilitated targeted drug delivery.
Conclusions:
- The developed DOX@aHA-DMA/Fe NPs are effective pH-responsive drug carriers for tumor-specific chemotherapy.
- The HA-mediated endocytosis and pH-triggered drug release contribute to improved therapeutic potential.
- These nanoparticles represent a promising strategy for enhancing cancer treatment by targeting acidic tumor microenvironments.
Keywords:
CD44 receptor-mediated endocytosisFe-based nanoparticlesendosomal pH-responsive hyaluronatetumor therapy
