Evaluating Dual-Targeted ECO/siRNA Nanoparticles against an Oncogenic lncRNA for Triple Negative Breast Cancer...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Differentiation antagonizing noncoding RNA (DANCR) is an oncogenic long noncoding RNA (lncRNA) frequently overexpressed in triple-negative breast cancer (TNBC).
• Targeting DANCR offers a potential therapeutic strategy for TNBC, a challenging cancer subtype with limited treatment options.
• Previous studies demonstrated the efficacy of RNA interference (RNAi) using ECO/siRNA nanoparticles to regulate DANCR.

Purpose of the Study:

• To develop dual-targeted nanoparticles for enhanced delivery of siDANCR to TNBC cells.
• To evaluate the therapeutic efficacy of these nanoparticles in vitro and in vivo.
• To assess the utility of magnetic resonance molecular imaging (MRMI) for monitoring treatment response.

Main Methods:

• Development of dual-targeted ECO/siDANCR nanoparticles targeting extradomain B fibronectin (EDB-FN) and cancer cell integrins.
• In vitro treatment of Hs578T (TNBC) and MCF-7 (ER+) cells to assess DANCR and EDB-FN down-regulation, and effects on invasion and spheroid formation.
• In vivo evaluation in mice bearing orthotopic xenografts using MRMI with an EDB-FN-targeted contrast agent (MT218) to monitor tumor response.

Main Results:

• In vitro studies showed significant down-regulation of DANCR and EDB-FN, with suppressed invasion and 3D spheroid formation.
• MRMI effectively differentiated between aggressive TNBC and ER+ MCF-7 tumors based on DANCR and EDB-FN expression.
• Dual-targeted ECO/siDANCR nanoparticles demonstrated superior tumor growth inhibition compared to controls and significantly reduced EDB-FN expression in TNBC tumors.

Conclusions:

• Dual-targeted ECO/siDANCR nanoparticles are effective in delivering therapeutic cargo to TNBC.
• MRMI with MT218 serves as a valuable tool for noninvasive evaluation of tumor response to targeted nanoparticle therapy.
• The combination of MRMI and dual-targeted nanoparticles offers a promising strategy for image-guided treatment of TNBC by targeting oncogenic lncRNAs.