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Updated: Jun 23, 2026
Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?
Published on: June 13, 2014
Polymeric nanoparticles for sustained down-regulation of annexin A2 inhibit prostate tumor growth
Arthur R Braden1, Michael T Kafka, Linda Cunningham
1Department of Molecular Biology and Immunology, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.
Abstract:
Prostate cancer is the most frequently diagnosed cancer and the second leading cause of cancer related death in Western men. In prostate intraepithelial neoplasia annexin A2 expression is absent however upon loss of androgen dependence annexin A2 is subsequently over-expressed. Regaining regulatory control of annexin A2 presents a means of therapy in the treatment of hormone refractory prostate cancers. In an effort to regain control of aberrant annexin A2 expression we have formulated poly lactide-co-glycolide (PLGA) nanoparticles loaded with pDrive-sh AnxA2 plasmid DNA. These nanoparticles are capable of sustained intracellular delivery of pDrive-sh AnxA2 plasmid DNA vector for long-term siRNA mediated down-regulation of annexin A2. Intra-tumoral administration of pDrive-sh AnxA2 loaded nanoparticles to xenograft prostate tumors in nude mice demonstrates an overall decrease in tumor growth. The decrease in tumor growth is through a reduction of annexin A2 and VEGF mRNA and protein levels within the tumor mass. Administration of blank nanoparticles demonstrated no alteration in tumor growth or annexin A2 and VEGF at either the mRNA or protein levels. Our findings suggest that the use of sustained-release polymeric nanoparticles for down-regulation of annexin A2 expression may serve as an effective adjuvant treatment option for prostate cancer.
Insights
Poly lactide-co-glycolide (PLGA) nanoparticles effectively delivered pDrive-sh AnxA2 plasmid DNA to prostate tumors, reducing tumor growth by down-regulating annexin A2 and VEGF. This offers a potential adjuvant therapy for hormone-refractory prostate cancer.
Area of Science:
- Oncology
- Nanotechnology
- Molecular Biology
Background:
- Prostate cancer is a leading cause of cancer death in Western men.
- Annexin A2 is overexpressed in hormone-refractory prostate cancer, making it a therapeutic target.
- Current treatments for advanced prostate cancer have limitations.
Purpose of the Study:
- To develop and evaluate poly lactide-co-glycolide (PLGA) nanoparticles for sustained delivery of pDrive-sh AnxA2 plasmid DNA.
- To assess the efficacy of annexin A2 down-regulation using siRNA-mediated gene silencing in prostate cancer models.
- To investigate the impact of annexin A2 reduction on tumor growth and related biomarkers.
Main Methods:
- Formulation of PLGA nanoparticles loaded with pDrive-sh AnxA2 plasmid DNA.
- Intra-tumoral administration of nanoparticles to xenograft prostate tumors in nude mice.
- Quantification of annexin A2 and VEGF mRNA and protein levels via RT-qPCR and Western blotting.
- Assessment of tumor growth and volume changes.
Main Results:
- Sustained intracellular delivery of pDrive-sh AnxA2 plasmid DNA was achieved.
- Intra-tumoral administration of loaded nanoparticles significantly reduced prostate tumor growth.
- Annexin A2 and VEGF mRNA and protein levels were decreased within the tumor mass.
- Blank nanoparticles showed no significant effect on tumor growth or biomarker levels.
Conclusions:
- Sustained-release PLGA nanoparticles are effective for delivering gene-silencing agents to prostate tumors.
- Down-regulation of annexin A2 using this nanoparticle system reduces tumor growth.
- This approach holds promise as an adjuvant therapy for hormone-refractory prostate cancer.
