Multi-Targeted and On-Demand Non-Coding RNA Regulation Nanoplatform against Metastasis and Recurrence of...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• MicroRNA (miR) dysregulation is a key driver of triple-negative breast cancer (TNBC) progression, including growth, metastasis, and recurrence.
• Targeting multiple dysregulated miRs simultaneously presents a significant therapeutic challenge in TNBC treatment.

Purpose of the Study:

• To develop a multi-targeting, on-demand nanoplatform (MTOR) for precise regulation of dysregulated miRs in TNBC.
• To evaluate the efficacy of MTOR in suppressing TNBC growth, metastasis, and recurrence in preclinical models.

Main Methods:

• MTOR nanoplatform functionalized with urokinase-type plasminogen activator peptide and hyaluronan ligands for active targeting of TNBC and cancer stem cells.
• Lysosomal hyaluronidase-triggered shell detachment and nuclear targeting of the TAT-enriched core.
• Simultaneous downregulation of microRNA-21 and upregulation of microRNA-205 expression within TNBC cells.

Main Results:

• MTOR demonstrated active targeting of TNBC cells and breast cancer stem cell-like cells (BrCSCs).
• On-demand miR regulation by MTOR led to significant inhibition of tumor growth, metastasis, and recurrence in various TNBC mouse models.
• Synergistic therapeutic effects were observed, highlighting the potential of MTOR in TNBC treatment.

Conclusions:

• The MTOR nanoplatform offers a novel strategy for precise, on-demand regulation of multiple miRs in TNBC.
• This approach shows significant promise for overcoming challenges in TNBC therapy by targeting growth, metastasis, and recurrence.
• MTOR opens new therapeutic avenues for managing aggressive breast cancer subtypes.