‘NICT’, next-generation cell permeation technology
The K Beauty Science Inc.
We are K-Beauty focused journal delivering what's new in the innovations of K-beauty
Research on cell-penetrating peptide (CPP) as a drug delivery technology is active. CPP is a peptide that performs the function of being able to pass through the cell membrane and reach the cytoplasm or nucleus. It all started in 1988 when, while studying Tat, the viral protein of the HIV virus, it was accidentally discovered that this protein was cell-permeable. Afterwards, people learned that numerous peptide sequences discovered in nature were cell-permeable and had different physical and chemical properties, such as cationic, amphipathic, and hydrophobic.
The reason CPP is attracting attention is because it can increase the cell permeability of non-permeable substances, including not only proteins but also DNA, RNA, and nanoparticles. To date, there are approximately 840 types of CPPs that are in development or have been developed worldwide. Although research and development using the latest biotechnology, such as microtechnology and nanotechnology, is being actively conducted, there are still many challenges that need to be solved in order to properly perform the drug delivery function. For example, the efficiency of passing through the cell membrane varies depending on the type of CPP, the exact mechanism of which is unknown. Even if it passes the cell membrane, many are trapped in endosomes with no way out leading to decomposition. In an environment where serum is present, the cell membrane penetration efficiency decreases by 50%.
To solve this problem, research and development of Advanced CPP, which has much higher cell penetration efficiency than existing CPP, is in full swing, and NICT (Neoregen IntraCellular delivery Technology) of Neoregen Biotech Co., Ltd. (CEO Jeong-min Seo) is emerging as a promising next-generation CPP.
?
High cell permeability and up to 80% endosomal escape efficacy
?After over 20 years of research and development, CEO Seo Jeong-min discovered a peptide derived from ‘Arabidopsis thaliana’ with excellent cell penetration function. Several peptides derived from Arabidopsis were isolated, and it was confirmed that some of the peptides had excellent cell penetration function even in an environment where serum was present, and that these peptides had the amino acid sequence of SEQ ID NO: 1 in common. Since then, research has been conducted on binding to other proteins or other protein delivery domains, including the amino acid sequence of SEQ ID NO: 1. Various substances that can bind to this CPP and move into cells have also been studied and NICT is the result of that long-term research.
NICT's core competitiveness lies in its unprecedented cell penetration rate. The amphipathic structure overcomes the limitations of existing cationic or hydrophobic structures, and the Natural Cyclic structure ensures stability and ease of production and expanded application. Above all, it has been recognized for its world-class endosomal escape efficacy. CPP or CPP complexes that enter the cell are trapped in endosomes, a biological membrane formed in the cytoplasm. At this time, they must escape from the endosome to avoid being decomposed in lysosomes. In the case of general CPP, not only is cell permeability low, but also the endosomal escape efficiency; only 1-2% reaches the intracellular target.
Currently, the CPP of Entrada Therapeutics, an American company that boasts the world's best endosomal escape efficiency, is at a maximum of 50%. On the other hand, NICT has excellent endosomal escape efficiency, with up to 80% reaching intracellular targets. As a result of research on the endosomal escape efficiency of NICT using gold nanoparticles, it was confirmed that they enter endosomes after 60 minutes and that up to 80% of endosomal escape occurs in 90 to 120 minutes. It's not just this. The number of molecules flowing into each unit cell of NICT is significantly higher than that of other companies' materials, and it is sufficiently effective even at low concentrations.
?
Making ACS MATERIALS LETTERS cover
Neorigen Biotech is proving NICT's technological competitiveness through various research. The NICT penetrating material is combined with FGF2 (fibroblast growth factor), EGF (epidermal growth factor), SOD (peroxidase removal enzyme), and type A light chain botulinum toxin (BTX), respectively, to create NR-FGF2, NR-EGF, NR-SOD, and NR-BTX and evaluated its cell penetration ability and efficacy.
Growth factors such as EGF and FGF2 induce cell regeneration and growth by activating intracellular signaling pathways by interacting with specific receptors present on the outer cell membrane, but they have the limitation of acting only outside the cell. On the other hand, NF-FGF2 applied with NICT permeation technology demonstrated that it primarily exerts biological activity outside the cell, penetrates directly into the cell, stays longer, and is re-released to surrounding cells to have a wide range of effects.
In addition, as a result of comparing the permeability of the NICT permeable material Ara27-FITC(NR) and Tat-CPP to human skin fibroblasts (HDF), the intracellular delivery efficiency of Ara27-FITC for 1 hour was 96.63%, with an efficiency of 4.17%. It was 23.17 times higher than Tat-CPP. Moreover, as time passed, there was a greater difference in the number of molecules introduced per unit cell. After 5 hours, there was a difference in efficiency of more than 500 times.
It's not just this. In the case of traditional botox, the complex structure of botulinum toxin, which is 900 kDa in size, has the potential to cause resistance or cause toxicity problems. On the other hand, NR-BTX significantly reduced toxicity and resistance problems by simplifying the existing Botox structure and using only the light chain domain. The light chain portion is 50 kDa in size and can effectively improve skin wrinkles by effectively cutting the SNAP25 protein within nerve cells.
领英推荐
In particular, last February, 'Photothermally Modulated Intracellular Delivery of Therapeutic Proteins Using Gold-Collagen Hybrid Nanoparticles' was conducted jointly with Professor Choi In-hee's research team in the Department of Life Sciences at the University of Seoul and it was published as the cover paper of 『ACS MATERIALS LETTERS』.
This is about light and heat-sensitive gold-collagen hydrogel nanoparticles (Au-CHP) that can deliver therapeutic proteins into cells. Bioactive proteins are added to Au-CHP made of biocompatible collagen, thermosensitive polymer, and gold as raw materials. The gist of the paper is that when irradiated with visible light after carrying gold nanoparticles, a photothermal conversion effect occurs, and this heat causes bioactive proteins to be released with high efficiency even within cells. By loading Neregen Biotech's NICT delivery material into nanoparticles based on biocompatible materials rather than lipid-based nanoparticles (LNPs), it achieves high cell penetration ability while avoiding the disadvantages of toxicity and low permeability of LNPs. It was selected as the cover paper in recognition of this innovative way in overcoming the problem.
Cosmetics ‘Generex’ using NICT technology
NICT is attracting special attention not only in the medical field but also in the cosmetics industry. This is because it is an important foundational technology that can be applied to the cosmetics business by effectively delivering macromolecules to the skin cells, maximizing the penetration rate of ingredients such as botox and growth factors.
The skin is made up of a complex barrier system. No matter how good an ingredient is, it is useless if it is not absorbed into the skin. The particle size that can be absorbed into the skin, confirmed through the SCI paper, is 500 Da (Dalton). The problem is that FGF2, which plays an important role in skin regeneration, is 17,123 Da, EGF, which helps strengthen the skin barrier and care for troubles, is 6,222 Da, and the size of botulinum protein, which is effective in improving skin sagging, and wrinkles, is 51,160 Da. In order to deliver these growth factors or macromolecules deep into the skin, special delivery techniques are needed, such as using a microneedle therapy system or injecting ingredients into the skin layer through microneedles and using high-frequency heat on the face. However, when NICT technology is applied, the unique functions of the material can be exerted just by applying the cosmetic product to the skin.
Neorigen Biotech registered NR-FGF2, NR-EGF, NR-SOD, NR-BTX, etc. in INCI (International Nomenclature of Cosmetic Ingredients) and launched ‘Generex’, a cosmetic product applying NICT technology. In fact, FGF2 growth factor is 4 times larger than EGF and cannot penetrate the epidermis. Generex with NICT, however, can penetrate the skin and has a dual function of skin and cell penetration; so when attached to regenerative protein, it has been verified that the skin cell regeneration effect is 100 times higher. In addition, the results of a four-week experiment using two materials, NR-EGF and NR-FGF2, applied to the skin once a day demonstrated that wrinkles were reduced by 34.4%. This is a result that is three times higher than the 10.7% wrinkle reduction rate of stem cell culture material applied to the skin twice a day. It is also worth noting that in this skin clinical trial, NR-EGF 1ppm showed a higher effect than general EGF 10ppm.
Neoregen Biotech is a biotechnology company that researches and develops medicines, cosmetics, and health foods that can deliver specific substances with high efficiency without damaging cells and skin based on NICT permeation platform technology.
CEO Seo Jeong-min graduated from the Department of Food Engineering at Seoul National University, worked as a post-doctor in the Food Microbiology Laboratory. He also worked as an assistant professor at the University of Nebraska, USA, where he conducted research on arteriosclerosis and vaccines. At the Catholic University of Korea Medical School, he conducted research on viral vaccines and stem cell regeneration.
CEO Seo is concurrently working as a research professor at Seoul National University's Graduate School of Dentistry, conducting research on peptides and periodontal stem cells.
For more information, please visit THE K BEAUTY SCIENCE website.
?