pH-Sensitive carboxymethyl chitosan-modified cationic liposomes for sorafenib and siRNA co-delivery

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Combination therapy using chemotherapeutic drugs and small interfering RNA (siRNA) targets multiple disease pathways for enhanced tumor suppression.
• Co-delivery of drugs and siRNA within a single nanocarrier is crucial for synergistic therapeutic effects.
• Developing effective delivery systems is key to improving cancer treatment outcomes.

Purpose of the Study:

• To develop a pH-sensitive liposome for the co-delivery of sorafenib (Sf) and siRNA to tumor sites.
• To evaluate the in vitro and in vivo antitumor efficiency of the developed nanocarrier.
• To assess the safety profile of the novel drug delivery system.

Main Methods:

• Carboxymethyl chitosan (CMCS) was coated onto cationic liposomes (CL) preloaded with Sf and siRNA, forming CMCS-SiSf-CL.
• In vitro studies involved evaluating siRNA condensation, protection from degradation, pH-sensitive drug release, and cellular uptake in HepG2 cells.
• In vivo experiments utilized a H22 cell-bearing Kunming mice model to assess antitumor efficacy and toxicity.

Main Results:

• CMCS-SiSf-CL efficiently condensed and protected siRNA from degradation.
• Sorafenib release from the liposomes demonstrated pH-sensitive behavior.
• In vitro and in vivo studies showed enhanced cellular uptake at tumor-relevant pH (6.5) and significant tumor growth inhibition compared to free sorafenib.
• The formulation exhibited low in vitro and in vivo toxicity.

Conclusions:

• CMCS-SiSf-CL is an effective nanocarrier for co-delivering Sf and siRNA, demonstrating pH-sensitive release and enhanced antitumor efficacy.
• This formulation shows promise as a safe and effective approach for tumor therapy.
• The developed liposomal system represents a significant advancement in targeted cancer treatment strategies.