Posters
Reconstitution of miRNA-205 in Docetaxel Resistant Prostate Cancer Cells: A Nanotherapeutic Approach
Presenting Author Academic/Professional Position
Faculty
Discipline/Specialty (Author 1)
Immunology and Microbiology
Discipline/Specialty (Author 2)
Immunology and Microbiology
Presentation Type
Poster
Discipline Track
Biomedical Science
Abstract Type
Research/Clinical
Abstract
Background: Prostate cancer (PrCa) is the second most diagnosed cancer and cause of death in men globally. Docetaxel (Dtxl) based first line chemotherapy is the main available therapeutic choice for PrCa patients. However, most (almost all) patients develop resistance to Dtxl treatment, making it difficult to treat such patients with no effective adjuvant therapy. Although cabazitaxel may be used to treat these patients, it is associated with many severe side effects including low white blood cells and allergic reactions. Therefore, finding an alternative strategy to reduce Dtxl resistance is of high importance for treating PrCa. miR-205 is a widely studied tumor suppressor microRNA in PrCa which is often downregulated in advanced stages of this cancer. Successful restoration of miR-205 may lead to reversal of Dtxl resistance and PrCa tumor regression.
Methods: We generated a self-assembly of miR-205 employing iron oxide magnetic nanoparticles (MNP) layered with polyethylene imine (PEI) polymer. An optimized nanoformulation (MNP-miR-205) was confirmed with DLS, gel retardation and biochemical analyses. Further, chemo-sensitizing and anti-cancerous properties of MNP-miR-205 were evaluated with Dtxl resistant PrCa cell lines and xenograft mouse models of these cell lines. Biodistribution of the formulation was additionally evaluated by incorporation of indocyanine green (ICG) dye to it.
Results: Our results indicated that MNP-miR-205 formulation is equipped with optimal particle size and zeta potential making it suitable for cancer cell delivery. Hemolysis data revealed that MNP-miR-205 is hemocompatible. This formulation showed an excellent cellular uptake via endocytosis related pathways escaping endosomal and lysosomal degradation. Additionally, our formulation exhibited chemo-sensitization properties by making Dtxl resistant cells more sensitive towards Dtxl treatment as demonstrated by induced apoptotic mediated cell death, Caspase 3/7 activity and decreased mitochondrial membrane potential. Moreover, our novel formulation indicated superior tumor uptake and anti-tumor activities as evident by high tumor accumulation and decreased tumor volume and weight with improved overall mice survival.
Conclusion: To conclude, this innovative nanoformulation addresses the unmet clinical need of not only developing chemo-sensitization treatment for Dtxl resistant PrCa but also providing a safer imaging platform, thus making it an excellent theranostic tool which can collectively result in improved prostate cancer management.
Also presented as an Oral Presentation.
Recommended Citation
Chauhan, Neeraj; Ghali, Eswara Naga Hanuma Kumar; Tiwari, Rahul; Enriquez, Iris; Baru, Rajasekhar; Chauhan, Subhash C.; and Yallapu, Murali M., "Reconstitution of miRNA-205 in Docetaxel Resistant Prostate Cancer Cells: A Nanotherapeutic Approach" (2025). Research Symposium. 117.
https://scholarworks.utrgv.edu/somrs/2025/posters/117
Reconstitution of miRNA-205 in Docetaxel Resistant Prostate Cancer Cells: A Nanotherapeutic Approach
Background: Prostate cancer (PrCa) is the second most diagnosed cancer and cause of death in men globally. Docetaxel (Dtxl) based first line chemotherapy is the main available therapeutic choice for PrCa patients. However, most (almost all) patients develop resistance to Dtxl treatment, making it difficult to treat such patients with no effective adjuvant therapy. Although cabazitaxel may be used to treat these patients, it is associated with many severe side effects including low white blood cells and allergic reactions. Therefore, finding an alternative strategy to reduce Dtxl resistance is of high importance for treating PrCa. miR-205 is a widely studied tumor suppressor microRNA in PrCa which is often downregulated in advanced stages of this cancer. Successful restoration of miR-205 may lead to reversal of Dtxl resistance and PrCa tumor regression.
Methods: We generated a self-assembly of miR-205 employing iron oxide magnetic nanoparticles (MNP) layered with polyethylene imine (PEI) polymer. An optimized nanoformulation (MNP-miR-205) was confirmed with DLS, gel retardation and biochemical analyses. Further, chemo-sensitizing and anti-cancerous properties of MNP-miR-205 were evaluated with Dtxl resistant PrCa cell lines and xenograft mouse models of these cell lines. Biodistribution of the formulation was additionally evaluated by incorporation of indocyanine green (ICG) dye to it.
Results: Our results indicated that MNP-miR-205 formulation is equipped with optimal particle size and zeta potential making it suitable for cancer cell delivery. Hemolysis data revealed that MNP-miR-205 is hemocompatible. This formulation showed an excellent cellular uptake via endocytosis related pathways escaping endosomal and lysosomal degradation. Additionally, our formulation exhibited chemo-sensitization properties by making Dtxl resistant cells more sensitive towards Dtxl treatment as demonstrated by induced apoptotic mediated cell death, Caspase 3/7 activity and decreased mitochondrial membrane potential. Moreover, our novel formulation indicated superior tumor uptake and anti-tumor activities as evident by high tumor accumulation and decreased tumor volume and weight with improved overall mice survival.
Conclusion: To conclude, this innovative nanoformulation addresses the unmet clinical need of not only developing chemo-sensitization treatment for Dtxl resistant PrCa but also providing a safer imaging platform, thus making it an excellent theranostic tool which can collectively result in improved prostate cancer management.
Also presented as an Oral Presentation.
