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Calcium phosphate-polymeric nanoparticle system for co-delivery of microRNA-21 inhibitor and doxorubicin
1Chemical Engineering Program, Department of Chemical and Environmental Engineering, University of Cincinnati, Cincinnati, OH, 45221-0012, United States.
Abstract:
Targeted combination therapy has shown promise to achieve maximum therapeutic efficacy by overcoming drug resistance. MicroRNA-21 (miR-21) is frequently overexpressed in various cancer types including breast and non-small cell lung cancer and its functions can be inhibited by miR inhibitor (miR-21i). A combination of miR-21i and a chemo drug, doxorubicin (Dox), can provide synergistic effects. Here, we developed a calcium phosphate (CaP)-coated nanoparticle (NP) formulation to co-deliver miR-21i along with Dox. This NP design can be used to deliver the two agents with different physiochemical properties. The NP formulation was optimized for particle size, polydispersity, Dox loading, and miR-21i loading. The NP formulation was confirmed to downregulate miR-21 levels and upregulate tumor suppressor gene levels. The cytotoxic efficacy of the combined miR-21i and Dox-containing NPs was found to be higher than that of Dox. Therefore, the CaP-coated hybrid lipid-polymeric NPs hold potential for the delivery of miR-21i and Dox.
Insights
This study developed calcium phosphate-coated nanoparticles to co-deliver a microRNA-21 inhibitor (miR-21i) and doxorubicin (Dox). This combination therapy enhances anti-cancer efficacy, offering a promising approach for targeted cancer treatment.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- MicroRNA-21 (miR-21) overexpression is common in breast and lung cancers, contributing to drug resistance.
- MicroRNA inhibitors (miR-21i) can counteract miR-21 function, and combining them with chemotherapy like doxorubicin (Dox) may yield synergistic effects.
Purpose of the Study:
- To develop and optimize a nanoparticle (NP) formulation for co-delivering miR-21i and Dox.
- To evaluate the efficacy of the combined therapy in preclinical cancer models.
Main Methods:
- Calcium phosphate (CaP)-coated hybrid lipid-polymeric nanoparticles were designed for co-delivery.
- Formulation optimization focused on particle size, polydispersity, and drug/inhibitor loading.
- In vitro studies assessed miR-21 downregulation, tumor suppressor gene upregulation, and cytotoxic efficacy.
Main Results:
- The optimized CaP-coated NPs successfully co-delivered both miR-21i and Dox.
- The NPs effectively downregulated miR-21 and upregulated tumor suppressor genes.
- The combination therapy demonstrated significantly higher cytotoxic efficacy compared to Dox alone.
Conclusions:
- CaP-coated hybrid NPs are a viable platform for co-delivering miR-21i and Dox.
- This targeted combination therapy shows potential for overcoming drug resistance and enhancing anti-cancer treatment efficacy.
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