pH-Sensitive Cationic Liposomes for Oridonin and siRNA Co-Delivery to Inhibit Triple-Negative Breast Cancer

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Triple-negative breast cancer (TNBC) presents a poor prognosis due to chemoresistance and stem-like properties.
• Targeting Connexin 26 (CX26) is a strategy to overcome TNBC therapeutic challenges.
• Simultaneous delivery of therapeutic agents is needed for enhanced efficacy.

Purpose of the Study:

• To develop pH-sensitive nanocomposite cationic liposomes for co-delivery of oridonin and siCX26 in TNBC.
• To evaluate the stability and therapeutic efficacy of the developed liposome system.
• To assess the potential of this system in inhibiting TNBC growth and inducing apoptosis.

Main Methods:

• Oridonin liposomes were prepared and then co-loaded with siCX26, modified with carboxymethyl chitosan (CMCS) to form pH-sensitive nanocomposite cationic liposomes (CMCS-Ori-siCX26-LipoPH+).
• Liposome stability was assessed by particle size and zeta-potential measurements.
• Apoptosis and intracellular signaling were evaluated using TUNEL staining and western blotting; in vivo studies were conducted in nude mice.

Main Results:

• The CMCS-Ori-siCX26-LipoPH+ liposomes maintained siRNA integrity for 8 hours and particle stability for 12 days.
• The liposomes significantly enhanced apoptosis in MDA-MB-231 cells at pH 6.5, delivering siRNA to the cytoplasm and preventing lysosomal degradation.
• In vivo studies demonstrated that CMCS-Ori-siCX26-LipoPH+ inhibited tumor growth and induced apoptosis in nude mice.

Conclusions:

• The developed pH-sensitive nanocomposite cationic liposome system effectively co-delivers oridonin and siCX26 to TNBC.
• This system demonstrates significant potential for inducing tumor cell apoptosis and inhibiting tumor growth in TNBC.
• The findings suggest a promising therapeutic strategy for managing aggressive TNBC subtypes.