Tumor-targeted liposomal RNAi therapy suppresses breast cancer and modulates tumor microenvironment

Area of Science:

• Nanomedicine
• Biotechnology
• Cancer Research

Background:

• Liposomes face challenges in clinical translation due to poor tumor selectivity and inefficient nucleic acid delivery.
• Multifunctional nanocarriers are needed to overcome these limitations for effective cancer therapy.

Purpose of the Study:

• To design and evaluate multifunctional liposomes for targeted breast cancer treatment.
• To integrate tumor targeting, intrinsic cytotoxicity, and anti-angiogenesis via RNA interference.

Main Methods:

• Liposomes were engineered with phenylboronic acid (PBA) for targeting, ginsenoside Rh2 (Rh2) for stabilization and cytotoxicity, and small interfering RNA against vascular endothelial growth factor (siVEGF).
• In vitro and in vivo studies were conducted using a 4T1 orthotopic breast tumor model.
• Evaluated tumor accumulation, cellular uptake, cytotoxicity, immune cell infiltration, tumor growth, and microvascular density.

Main Results:

• PBA-modified liposomes demonstrated enhanced tumor accumulation and cellular uptake.
• The combination of Rh2 cytotoxicity and VEGF silencing showed synergistic antitumor activity.
• RhPLIPO-siVEGF significantly reduced tumor growth and microvascular density, with increased T cell and M1 macrophage infiltration.

Conclusions:

• The multifunctional liposomal system offers a potent and versatile nanoplatform for targeted breast cancer therapy.
• This approach integrates targeting, direct cytotoxicity, and RNA interference for enhanced therapeutic outcomes.
• The developed liposomes show promise for clinical translation with minimal adverse effects.