Researchers have created “nanomachines” that use mechanical molecular motion to penetrate and destroy cells.
Cancer is a condition in which certain cells in the body grow uncontrollably and spread to other parts of the body. Cancer cells are constantly being distributed, invading surrounding tissues and creating solid tumors. Most cancer treatments kill cancer cells.
As of 2020, an estimated 1.8 million new cases of cancer have been diagnosed in the United States, killing 600,000 people. Breast cancer, lung cancer, prostate cancer and colon cancer are the most common cancers. The average age of a cancer patient is 66 years at diagnosis, and people between the ages of 65 and 74 make up 25% of all new cancer diagnoses.
Proteins are involved in all biological processes and use the body’s energy to change their structure through mechanical movements. They are referred to as biological “nanomachines” because even small structural changes in proteins have a significant impact on biological processes. To establish movement in the cellular environment, researchers have focused on the development of nanomachines that mimic proteins. However, cells use a variety of mechanisms to defend against the influence of these nanomachines. This limits the significant mechanical movements of nanomachines that could be used for medical purposes.
The research team led by Dr. Youngdo Jeong of the Korean Institute of Science and Technology (KIST) has reported on the development of a new biochemical nanomachine that penetrates and kills cell membranes. they fold and spread in certain cellular environments, such as cancer cells. They collaborated with teams from Professor Sang Kyu Kwak of the School of Energy and Chemical Engineering and Professor Ja-Hyoung Ryu of the Department of Chemistry at the Ulsan National Institute of Science and Technology (UNIST) and Dr. Chaekyu Kim of Fusion Biotechnology. , Inc.
The joint research team focused on the hierarchical structure of proteins, in which the axis of the large structure and the mobile units are hierarchically separated. Therefore, only specific parts can be moved around the axis. Most of the existing nanomachines are designed so that the movable components and shafts of the large structure are in the same layer. Thus, these components undergo simultaneous movement, which complicates the desired control of a specific part.
A hierarchical nanomachine was manufactured by synthesizing and combining gold nanoparticles with a diameter of 2 nm, molecules that can be folded and expanded depending on the surrounding environment. This nanomachine was composed of mobile organic molecules and inorganic nanoparticles that functioned as a major axis structure and defined movement and direction in such a way that when it reached the cell membrane it caused a mechanical folding / deployment, and the nanomachine was inserted directly. cells, destroying organelles and causing apoptosis. This new method directly kills cancer cells through mechanical movements without anti-cancer drugs, compared to capsule-type nanoparticles that deliver therapeutic drugs.
A latch molecule was then placed in the nanomachine to control the mechanical movement of selectively killing cancer cells. The threaded latch molecule was designed for release only in a low pH environment. Thus, in normal cells with a relatively high pH (approximately 7.4), the movements of nanomachines were limited and they were unable to penetrate the cells. However, in a low-pH environment around cancer cells (approximately 6.8), latch molecules were released, causing mechanical movement and cell internalization.
Dr. Jeong said: “The developed nanomachine was inspired by proteins that perform biological functions, changing their shape depending on the environment. to overcome the side effects of existing chemotherapy. ”
Reference: Youngdo Jeong, Soyeong Jin, L. Palanikumar, Huyeon Choi, Eunhye Shin, Eun Min Go, Changjoon Keum, Seunghwan Bang, Dongkap Kim, “Stimuli-Responsive Adaptive Nanotoxin to Directly Penetrate the Cellular Membrane by Molecular Folding and Unfolding” Lee, Minsoo Kim, Hojun Kim, Kwan Hyi Lee, Batakrishna Jana, Myoung-Hwan Park, Sang Kyu Kwak, Chaekyu Kim and Ja-Hyoung Ryu, March 2, 2022, American Chemical Society Journal.
DOI: 10.1021 / jacs.2c00084