Scientists develop “nanomachines” that can penetrate and kill cancer cells

A research group from the Korea Institute of Science and Technology has developed “nanomachines,” which use mechanical molecular movements to penetrate and destroy cells. Selective penetration of cancer cells is also possible using a latch molecule released near the cancer cells.

Researchers have created “nanomachines” that use mechanical molecular movements to enter and destroy cells.

Cancer is a condition in which certain cells in the body grow out of control and spread to other regions of the body. Cancer cells divide continuously, causing them to invade surrounding tissues and form solid tumors. Most cancer treatments involve killing cancer cells.

According to 2020 estimates, 1.8 million new cases of cancer have been diagnosed in the United States and 600,000 people have died from the condition. Breast cancer, lung cancer, prostate cancer and colon cancer are the most common cancers. The average age of a cancer patient at the time of diagnosis is 66, and individuals between the ages of 65 and 74 account for 25% of all new cancer diagnoses.

Proteins are involved in every biological process and use the body’s energy to change their structure through mechanical movements. They are referred to as biological “nanomachines” since even small structural changes in proteins have a substantial impact on biological processes. To implement motion in the cellular environment, the researchers focused on developing nanomachines that mimic proteins. However, cells use a variety of mechanisms to defend themselves against the effect of these nanomachines. This limits any relevant mechanical movement of nanomachines that could be used for medical purposes.

The research team led by Dr Youngdo Jeong of the Center for Advanced Biomolecular Recognition at the Korea Institute of Science and Technology (KIST) has reported the development of a new biochemical nanomachine that penetrates the cell membrane and kills the cell through the molecular movements of folding. and unfold in certain cellular environments, such as cancer cells. They collaborated with the teams of Professor Sang Kyu Kwak of the School of Energy and Chemical Engineering and Professor Ja-Hyoung Ryu of the Chemistry Department of Ulsan National Institute of Science and Technology (UNIST) and of Dr. Chaekyu Kim of Fusion Biotechnology, Inc.

System of molecular machines with nanomachines

The nanomachine, developed by the joint research team KIST-UNIST, selectively penetrates and kills cancer cells, as well as its mechanism of action. Credit: Korea Institute of Science and Technology (KIST)

The joint research group 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 move around the axis. Most of the existing nanomachines have been designed so that the moving components and the axis of the large structure are present on the same layer. Therefore, these components undergo simultaneous movement, which complicates the desired control of a specific part.

A hierarchical nanomachine was fabricated by synthesizing and combining 2 nm diameter gold nanoparticles with molecules that can be folded and unfolded based on their surroundings. This nanomachine was composed of mobile organic molecules and inorganic nanoparticles to function as large axis structures and define motion and direction in such a way that once it reached the cell membrane it resulted in a mechanical folding / unfolding motion that carried the nanomachine to penetrate directly into the cell, destroying organelles and inducing apoptosis. This new method directly kills cancer cells through mechanical movement without anticancer drugs, in contrast to capsule nanocarriers that deliver therapeutic drugs.

Next, a latch molecule was threaded into the nanomachine to control mechanical motion to selectively kill cancer cells. The threaded latch molecule was designed to be released only in a low pH environment. Therefore, in normal cells with a relatively high pH (about 7.4), the movements of the nanomachines were limited and could not penetrate the cell. However, at the low pH environment around the tumor cells (approximately 6.8), the latch molecules were unbound, inducing mechanical movement and cell penetration.

Dr. Jeong said: “The developed nanomachine was inspired by proteins that perform biological functions by changing their shape according to their environment. We propose a new method to directly penetrate cancer cells to kill them through the mechanical movements of molecules attached to drug-free nanomachines. This could be a new alternative to overcome the side effects of existing chemotherapy ”.

Reference: “Stimulating adaptive nanotoxin to penetrate cell membrane directly by molecular folding and opening” by Youngdo Jeong, Soyeong Jin, L. Palanikumar, Huyeon Choi, Eunhye Shin, Eun Min Go, Changjoon Keum, Seunghwan Bang, Dongkap Kim Seungho 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, Journal of the American Chemical Society.
DOI: 10.1021 / jacs.2c00084

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