Self-assembled peptide nanostructures targeting death receptor 5 and encapsulating paclitaxel as a multifunctional...

Area of Science:

• Biomaterials Science
• Nanotechnology
• Cancer Therapeutics

Background:

• Targeted drug delivery systems aim to enhance cancer therapeutic efficacy and reduce toxicity.
• Death receptor 5 (DR5) is highly expressed on cancer cells and can trigger programmed cell death.
• Developing nanostructures that target DR5 offers a dual targeting and therapeutic strategy.

Purpose of the Study:

• To create and evaluate peptide amphiphile (PA) nanofibers that self-assemble and target DR5 for cancer therapy.
• To investigate the enhanced binding affinity and cytotoxicity of coassembled DR5-targeting PAs.
• To assess the *in vivo* antitumor activity of DR5-targeting nanostructures combined with paclitaxel.

Main Methods:

• Synthesized peptide amphiphiles (PAs) with dimeric, cyclic peptides for DR5 targeting.
• Self-assembled PAs into cylindrical supramolecular nanofibers.
• Coassembled DR5-targeting PAs with pegylated PAs.
• Evaluated *in vitro* cytotoxicity and *in vivo* antitumor activity.

Main Results:

• The dimeric, cyclic peptide PA self-assembled into nanofibers targeting DR5.
• Coassembly with pegylated PA enhanced binding affinity to DR5 compared to monomeric PAs.
• The nanostructures exhibited *in vitro* cytotoxicity.
• *In vivo* studies showed potent antitumor activity when combined with paclitaxel.

Conclusions:

• Peptide-based supramolecular nanostructures can be engineered for dual targeting and therapeutic functions.
• DR5-targeting nanofibers demonstrate potential as effective cancer therapeutics.
• These nanostructures show promise for combination therapy with existing chemotherapeutics like paclitaxel.