Improved melanoma suppression with target-delivered TRAIL and Paclitaxel by a multifunctional nanocarrier

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Malignant melanoma exhibits resistance to apoptosis-inducing agents like TRAIL due to low death receptor expression.
• Combination therapy with paclitaxel (PTX) and TRAIL shows enhanced anti-melanoma effects.
• Targeted drug delivery systems are needed to overcome resistance and improve therapeutic outcomes.

Purpose of the Study:

• To develop a tumor microenvironment-responsive, liposomal co-delivery system for TRAIL and PTX targeting malignant melanoma.
• To enhance the anti-melanoma efficacy of TRAIL through synergistic combination with PTX.
• To investigate the targeting, drug release, and internalization mechanisms of the novel delivery system.

Main Methods:

• Development of a liposomal system (TRAIL-[Lip-PTX]C18-TR) for co-delivering TRAIL and PTX.
• Surface modification with a stearyl chain fused pH-sensitive cell-penetrating peptide (C18-TR) for melanoma targeting (αvβ3 integrin) and pH-triggered release.
• In vitro efficacy studies (IC50) and in vivo tumor inhibition assays.
• Mechanistic studies to elucidate the role of death receptor upregulation.

Main Results:

• The TRAIL-[Lip-PTX]C18-TR system demonstrated superior in vitro efficacy compared to other formulations.
• An impressive in vivo tumor inhibition rate of 93.8% was achieved.
• Paclitaxel (PTX) was found to upregulate death receptors DR4/5, contributing to the synergistic effect.
• The C18-TR modification facilitated specific melanoma targeting and pH-responsive drug release.

Conclusions:

• The developed liposomal co-delivery system significantly enhances TRAIL-based therapy against malignant melanoma.
• The system offers a promising platform for co-delivering therapeutic agents for melanoma treatment.
• The combination strategy and targeted delivery overcome drug resistance and improve therapeutic outcomes.