NGR-modified nanovesicles target ALKBH5 to inhibit ovarian cancer growth and metastasis
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Surface-enhanced Resonance Raman Scattering Nanoprobe Ratiometry for Detecting Microscopic Ovarian Cancer via Folate Receptor Targeting
Published on: March 25, 2019
Cheng Du1, DaLu Wang2, Boquan Zhang3
1Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang 110004, China.
Abstract:
Background: Immunotherapy resistance in ovarian cancer (OC) poses a significant clinical hurdle. This study aims to investigate the potential of NGR-modified biomimetic nanovesicles (NGR-BNVs) for delivering ALKBH5 siRNA to reverse this resistance. Methods: In vitro and in vivo experiments were conducted to assess the efficiency of NGR-modified nanovesicles in delivering ALKBH5 siRNA. OC cell proliferation was evaluated, and apoptosis induction was measured. A mouse xenograft model was utilized to examine the effects on tumor volume and metastasis. Tumor immune microenvironment (TIME) analysis was performed to determine changes in immune cell proportions and immunomodulatory factors. Results: NGR-modified nanovesicles effectively delivered ALKBH5 siRNA, leading to a significant inhibition of OC cell proliferation and apoptosis induction. Treated groups in the mouse xenograft model exhibited reduced tumor volume and decreased metastatic signals. Analysis of the immune microenvironment revealed an increased proportion of CD8+ T cells, reduced Tregs and MDSCs, and notable changes in key immunomodulatory factors. Conclusion: This study highlights the potential of NGR-modified BNVs for overcoming immunotherapy resistance in OC by delivering ALKBH5 siRNA, resulting in modulation of the immune microenvironment and promising therapeutic outcomes.
Insights
NGR-modified nanovesicles delivering ALKBH5 siRNA show promise in overcoming ovarian cancer immunotherapy resistance by modulating the tumor immune microenvironment and reducing tumor growth and metastasis.
Area of Science:
- Oncology
- Nanomedicine
- Immunotherapy
Background:
- Ovarian cancer (OC) immunotherapy resistance is a major clinical challenge.
- Novel therapeutic strategies are needed to overcome this resistance.
Purpose of the Study:
- To investigate NGR-modified biomimetic nanovesicles (NGR-BNVs) for delivering ALKBH5 siRNA to reverse OC immunotherapy resistance.
- To evaluate the therapeutic efficacy and immune-modulating effects of NGR-BNVs carrying ALKBH5 siRNA.
Main Methods:
- In vitro and in vivo studies using OC cell lines and a mouse xenograft model.
- Assessment of nanovesicle delivery efficiency, OC cell proliferation, apoptosis, tumor volume, and metastasis.
- Analysis of the tumor immune microenvironment (TIME) including immune cell populations and immunomodulatory factors.
Main Results:
- NGR-BNVs effectively delivered ALKBH5 siRNA, inhibiting OC cell proliferation and inducing apoptosis.
- Significant reduction in tumor volume and metastasis was observed in treated mice.
- Modulation of TIME with increased CD8+ T cells and decreased Tregs and MDSCs.
Conclusions:
- NGR-modified biomimetic nanovesicles are a promising platform for delivering ALKBH5 siRNA in ovarian cancer.
- This approach can overcome immunotherapy resistance by reprogramming the tumor immune microenvironment.
- NGR-BNVs demonstrate potential for improved therapeutic outcomes in ovarian cancer.
