SapC-DOPS nanovesicles as targeted therapy for lung cancer

Area of Science:

• Oncology
• Nanomedicine
• Biochemistry

Background:

• Lung cancer remains a leading cause of cancer-related mortality globally.
• Current treatments have limitations, necessitating novel therapeutic strategies.
• Lysosomal proteins and phospholipids can form nanovesicles with potential therapeutic applications.

Purpose of the Study:

• To evaluate the in vitro and in vivo efficacy of Saposin C-dioleoylphosphatidylserine (SapC-DOPS) nanovesicles for lung cancer treatment.
• To investigate the pH-dependent binding and cytotoxicity of SapC-DOPS.
• To assess the tumor-targeting and therapeutic effects of SapC-DOPS in preclinical models.

Main Methods:

• Assembly of SapC-DOPS nanovesicles.
• In vitro assessment of nanovesicle binding to lung tumor cells at varying pH.
• Cytotoxicity assays and mitochondrial membrane potential measurements.
• In vivo fluorescence tracking and efficacy studies in human lung cancer xenografts.

Main Results:

• SapC-DOPS binding to lung cancer cells was enhanced at acidic pH.
• Cytotoxicity of SapC-DOPS correlated positively with cell surface phosphatidylserine levels.
• In vivo studies demonstrated specific targeting of lung cancer xenografts by SapC-DOPS.
• Systemic SapC-DOPS therapy significantly inhibited tumor growth and induced apoptosis.

Conclusions:

• SapC-DOPS nanovesicles exhibit selective antitumor activity against lung cancer.
• The acidic tumor microenvironment enhances SapC-DOPS binding and efficacy.
• SapC-DOPS represents a promising biotherapeutic agent for lung cancer treatment.