New Fluorescent Protein Nanoparticles for Cancer Targeting and Imaging

What is it about?

Recently, real-time fluorescence image-guided surgery has been increasingly important, because it improves precision and outcomes of cancer surgery and leads to higher cancer survival rates. To improve the performance of image-guided surgery, a double-Layered Fluorescent Protein Nanoparticle was developed with higher fluorescence emission and photostability than a conventional fluorescent dye (Cy5.5). Hepatitis B virus (HBV) capsid was genetically engineered to develop double-layered mCardinal protein nanoparticle (mC-DL-HBVC) with cancer cell receptor-binding peptides. The mC-DL-HBVCs actively targeted cancer cells through cancer cell receptor-mediated endocytosis and showed excellent performance in in vivo cancer cell imaging.

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Why is it important?

Although there are currently developed fluorescent probes for the real-time fluorescence image-guided surgery, the conventional near infrared (NIR) fluorescent probes for deep tissue imaging, such as inorganic (CdSe, ZnS, etc.) and synthetic organic dyes (Cy5, Cy5.5, etc.), fall short for this application because of their in vivo toxicity and undesirable binding to various proteins in the blood such as albumin. One approach that encapsulates fluorescent probes within small synthetic cages (e.g. liposomes or hollow silica spheres) is not safe enough to solve the underlying issues of toxicity resulting from the possibility of long-term accumulation in the body. Additionally, the fluorophore encapsulation within a synthetic cage suffers from several drawbacks, including reduced fluorescence and leakage problems. Also, it is difficult to chemically synthesize the cage with constant size and composition. Based on these demands, researchers from Korea University, South Korea, Purdue University, USA, and Korea Institute of Science and Technology (KIST), South Korea, developed a new method of fluorophore encapsulation using a biological protein nanoparticle, i.e. Hepatitis B virus capsid (HBVC), as a nanostructure cage of uniform size and composition. A far-red fluorescent protein (mCardinal) was genetically attached to both the inner and outer surfaces of HBVC, which gives rise to double-layered mCardinal HBVC nanoparticle (mC-DL-HBVC). The mC-DL-HBVC shows an enhanced fluorescence and photostability and is efficiently internalized by cancer cells and significantly photostable against intracellular degradation. The mC-DL-HBVC effectively detected tumor in live mice with enhanced tumor targeting and imaging efficiency with far less accumulation in the liver, compared to a conventional fluorescent dye, Cy5.5. The developed fluorescent material would be a highly promising contrast agent for in vivo tumor fluorescence imaging.