Sequential Rocket-Mode Bioactivating Ticagrelor Prodrug Nanoplatform Combining Light-Switchable Diphtherin Transgene...

Area of Science:

• Biomedical Engineering
• Oncology
• Nanotechnology

Background:

• Platelets significantly increase breast cancer metastasis risk.
• Existing light-switchable diphtheria toxin A fragment (DTA) gene systems (LightOn) show therapeutic promise but lack antimetastatic effects.

Purpose of the Study:

• To develop an innovative drug delivery system combining a light-switchable DTA transgene with a ticagrelor (Tig) prodrug for enhanced breast cancer treatment.
• To create a system that targets DTA delivery and inhibits platelet activity via sequential Tig release triggered by tumor microenvironment factors.

Main Methods:

• Development of a sequential rocket-mode bioactivating drug delivery system (pDTA-Tig@CML) using cell membrane fusion liposomes (CML).
• Loading CML with light-switchable DTA (pDTA) and a ticagrelor (Tig) prodrug.
• Investigating the system's efficacy in vitro and in vivo for targeted drug delivery, platelet inhibition, and anti-metastatic effects.

Main Results:

• pDTA-Tig@CML sequentially releases Tig and pDTA, effectively suppressing platelet activity and mitigating platelet-driven breast cancer metastasis.
• The system demonstrated enhanced tumor aggregation, restrained tumor growth and metastasis, and reduced levels of ADP, ATP, TGF-β, and P-selectin in vitro and in vivo.
• Successful combination of the bioactivating Tig prodrug nanoplatform with the LightOn system.

Conclusions:

• pDTA-Tig@CML is a promising light-switchable DTA transgene system for breast cancer treatment.
• The developed system offers a novel bioactivating prodrug platform with significant antimetastatic capabilities.
• This approach highlights the synergistic benefits of combining targeted gene therapy with platelet inhibition for improved cancer outcomes.