Bi-specific tenascin-C and fibronectin targeted peptide for solid tumor delivery

Area of Science:

• Biochemistry
• Oncology
• Nanotechnology

Background:

• Oncofetal proteins, fibronectin (FN-EDB) and tenascin-C (TNC-C), are upregulated in malignant tissues.
• These proteins are potential targets for antibody-based cancer therapies.

Purpose of the Study:

• To identify a novel peptide targeting both FN-EDB and TNC-C.
• To evaluate the efficacy of PL1-functionalized nanocarriers for glioblastoma (GBM) therapy.

Main Methods:

• Peptide phage biopanning was used to discover the PL1 peptide.
• PL1-functionalized iron oxide nanoworms and silver nanoparticles were tested in glioblastoma and prostate carcinoma xenografts.
• Therapeutic efficacy was assessed in GBM-bearing mice using PL1-targeted nanocarriers loaded with a proapoptotic peptide.

Main Results:

• The novel peptide PL1 (PPRRGLIKLKTS) was identified, interacting with both FN-EDB and TNC-C.
• Systemic administration of PL1-functionalized nanoparticles showed homing to glioblastoma and prostate carcinoma xenografts, as well as to non-malignant angiogenic neovessels.
• PL1-targeted nanocarrier treatment significantly reduced GBM tumor growth and increased mouse survival, while untargeted particles had no effect.

Conclusions:

• The PL1 peptide serves as an effective affinity ligand for targeting FN-EDB and TNC-C.
• PL1-functionalized nanocarriers demonstrate potential for targeted delivery of diagnostic and therapeutic agents to solid tumor microenvironments.
• This peptide-based targeting strategy offers a promising approach for enhancing cancer therapy efficacy.