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Functional Nanocomplexes with Vascular Endothelial Growth Factor A/C Isoforms Improve Collateral Circulation and
Bokang Qiao1, Jing-Jun Nie2, Yihui Shao1
1Key Laboratory of Remodeling-Related Cardiovascular Diseases (Ministry of Education), Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing Anzhen Hospital Affiliated to Capital Medical University, Beijing, 100029, China.
Heparin polysaccharide nanoparticles (HepNP) effectively deliver therapeutic proteins like VEGF-A and VEGF-C for cardiovascular disease treatment. This novel system enhances protein stability and targeted delivery, significantly improving cardiac function post-myocardial infarction.
Area of Science:
- Biomaterials Science
- Cardiovascular Medicine
- Drug Delivery Systems
Background:
- Protein-based therapies offer potential for treating cancer, immunological, and cardiovascular diseases.
- Instability and immunogenicity of proteins necessitate advanced delivery systems.
- Heparin polysaccharide nanoparticles (HepNP) are explored as a novel delivery vehicle for therapeutic proteins.
Purpose of the Study:
- To develop and evaluate a HepNP-based delivery system for vascular endothelial growth factor (VEGF) proteins for myocardial infarction (MI) therapy.
- To investigate the efficacy of dual delivery of VEGF-C and VEGF-A using HepNP for improved cardiac function and reduced scar formation.
- To assess the potential of HepNP for broader applications in protein-based therapies.
Main Methods:
- HepNP were synthesized and characterized for their ability to condense VEGF proteins.
- VEGF-C and VEGF-A were complexed with HepNP to form Hep@VEGF-C and Hep@VEGF-A.
- These complexes were administered intravenously in a rat model of MI using a graded delivery strategy.
- Cardiac function, scar formation, angiogenesis, and lymphangiogenesis were assessed post-treatment.
Main Results:
- HepNP efficiently condensed VEGF due to heparin's unique chemical properties.
- A graded delivery strategy of Hep@VEGF-C followed by Hep@VEGF-A significantly improved cardiac function (≈+74%) and reduced scar size (≈-39%) in MI models.
- Hep@VEGF-C promoted lymphangiogenesis and reduced edema, while Hep@VEGF-A's pro-angiogenic effects were limited by increased vascular permeability.
Conclusions:
- HepNP provides a stable and effective platform for delivering functional proteins like VEGF for cardiovascular disease treatment.
- The developed graded delivery system of VEGF-C and VEGF-A using HepNP offers a promising therapeutic strategy for myocardial infarction.
- HepNP's versatility in binding growth factors suggests broad applicability in treating various serious diseases requiring protein therapy.
