A research group led by Prof. WU Aiguo at the Ningbo Institute of Materials Technology and Engineering (NIMTE) of the Chinese Academy of Sciences (CAS), in cooperation with Prof. Dan Larhammar's group at Uppsala University, has proposed a D-peptide ligand of neuropeptide Y receptor Y₁, which can serve as nanocarriers to facilitate the traversal of the blood brain barrier (BBB) and thus targets gliomas efficiently. Results were published in Nano Today. 

Tumor is one of the most serious diseases posting threats to human life and health. How to achieve accurate diagnosis and treatment of tumor has become an important scientific issue of common concern in multidisciplinary fields such as biology and materials science. And BBB restricts the entry of drugs into the brain tissue, hindering the effective diagnosis and treatment of brain tumors, such as gliomas. 

Based on the structure-guided design in the lab, the researchers at NIMTE developed a D-peptide ligand of Y₁ receptor, ^D[Asn²⁸, Pro³⁰, Trp³²]-NPY(25-36)( ^DAPT). 

Experimental and computational validation results indicate that when interacting with Y₁ receptor, ^DAPT possesses higher affinity than the corresponding peptide with standard L-amino acids (^LAPT), since the quantity of hydrogen bonds for ^DAPT is 2.5 times higher than ^LAPT.  

In addition, a transcytosis experiment was conducted by virtue of an in vitro BBB model, demonstrating that ^DAPT modified nanomicelles perform superior efficiency in crossing the BBB comparing with ^LAPT and can specifically targets gliomas. 

According to in vivo studies, ^DAPT nanomicelles show great potential in improving photothermal therapeutic efficacy and photoacoustic tumor imaging efficiency, when loaded with a near infrared photosensitizer IRDye780. 

This study may shed light on the mechanism exploration of the neuropeptide Y crossing BBB, and facilitate the accurate diagnosis and treatment of gliomas and other central nervous system diseases.   

This work was financially supported by the Natural Science Foundation of China, the Swedish Foundation for International Cooperation in Research and Higher Education, the Science & Technology Bureau of Ningbo City, the Chinese Academy of Sciences President’s International Fellowship Initiative, and the Excellent Member of Youth Innovation Promotion Association Foundation of CAS.

The D-peptide ligand of Y₁ receptor serves as nanocarrier crossing the blood brain barrier and targets gliomas (Image by NIMTE)