HA-DOPE-Modified Honokiol-Loaded Liposomes Targeted Therapy for Osteosarcoma

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Osteosarcoma (OS) is a prevalent bone cancer with high metastatic potential and poor prognosis.
• Honokiol (HNK), a traditional Chinese medicine component, exhibits anti-tumor properties but faces limitations due to poor water solubility and lack of drug targeting.
• Developing targeted drug delivery systems is crucial for improving OS therapeutic efficacy.

Purpose of the Study:

• To develop and evaluate HNK-loaded liposomes modified with hyaluronic acid-phospholipid conjugates (HA-DOPE) for enhanced osteosarcoma treatment.
• To leverage the CD44-mediated interaction of hyaluronic acid (HA) for targeted drug delivery to OS cells.
• To investigate the in vitro and in vivo antitumor efficacy and safety of the novel nanocarrier system.

Main Methods:

• HNK-loaded liposomes were prepared using thin-film hydration and sonication.
• Liposomes were modified with HA-DOPE via sonication and co-extrusion to form HA-DOPE@Lips/HNK.
• Characterization included particle size, zeta potential, PDI, stability, and transmission electron microscopy.
• In vitro evaluation involved cellular uptake, cell viability, apoptosis, cell cycle, and mitochondrial activity assays.
• In vivo studies assessed biodistribution, tumor growth inhibition in OS xenografts, and safety.

Main Results:

• HA-DOPE@Lips/HNK exhibited optimal particle size (146.20±0.26 nm), PDI (0.20±0.01), and zeta potential (-38.45±0.98 mV).
• Encapsulation rate and drug loading were 80.14±0.32% and 3.78±0.09%, respectively.
• In vitro, HA-DOPE@Lips/HNK inhibited proliferation, induced apoptosis, arrested the cell cycle, and disrupted mitochondrial activity.
• In vivo, the nanocarrier demonstrated targeted tumor delivery, significant tumor growth inhibition, and no obvious toxicity to normal tissues.

Conclusions:

• HA-DOPE@Lips/HNK effectively delivers HNK to tumor sites, exhibiting potent in vitro and in vivo antitumor activity.
• The HA-DOPE modification enhances the therapeutic effects of HNK in osteosarcoma.
• This nanocarrier system presents a promising strategy for improving drug delivery and therapeutic outcomes in osteosarcoma treatment.