Nav: Home

Researchers develop molecular assembly method for cancer therapy and diagnostics

June 14, 2018

Biophysicists have developed a method for modifying the surface of micro- and nanoparticles -- tiny structures measuring between a thousandth and a millionth of a millimeter --by covering them with biological molecules. Engineered in this way, the particles can serve as both therapeutic and diagnostic agents, delivering drugs to cancer cells.

The paper was published in the journal ACS Applied Materials & Interfaces. Its authors are researchers from the Moscow Institute of Physics and Technology (MIPT), the Institute of Bioorganic Chemistry of the Russian Academy of Sciences (IBCh RAS), National Research Nuclear University MEPhI, Sechenov University, and Macquarie University (Australia).

Magic bullet: Seek and cure

The concept of a "magic bullet" was originally formulated around 1900 by Paul Ehrlich, the winner of the 1908 Nobel Prize in physiology or medicine. He envisioned drugs that would have a component which recognizes the pathogen in the body and another component that acts on the target. Usually, such drugs target receptors on the surface of the damaged cells. These receptors also allow the agent to recognize the cell. A universal system of this kind can be used for diagnostics, therapy, or both. When therapy and diagnostics are combined, this is known as theranostics.

To make a system incorporating a therapeutic and a diagnostic component, a "molecular glue" is needed for holding the two parts together. This glue can be realized as proteins capable of forming a stable complex by binding to each other. One of the most stable complexes of this kind is the barnase-barstar protein pair. There is a value known as the binding constant that characterizes how strongly the molecules in a complex are coupled. The binding constant of the barnase-barstar complex is 1,000 to 1 million times greater than those of the antigen-antibody complexes, which are the basis of our immune response.

Barnase and barstar can be used to engineer various functional modules for theranostics. For example, barnase can be bound to therapeutic agents -- antibodies, drugs, fluorescent molecules, etc. -- while barstar can be fused with a targeting agent. This concept was suggested by Sergey Deyev, the head of Molecular Immunology Laboratory of IBCh RAS. The two modules are then combined, forming a bifunctional compound, which has therapeutic and diagnostic properties, and enables targeted drug delivery. By fusing barnase and barstar with various therapeutic and diagnostic molecules, researchers can develop a range of theranostic agents based on the same principle. These molecular structures can be carried on the surface of nano- or microparticles. The particles themselves can have auxiliary properties, including fluorescence or the ability to be destroyed when exposed to radiation, killing off the surrounding harmful cells, such as cancer cells. Dozens of molecular structures of different types can be deposited on a tiny particle, potentially increasing its therapeutic effects.

Molecular assembly kit

The notion of using nano- and microparticles to deliver drugs is being actively researched in many laboratories. The Russian and Australian researchers developed a nanoparticle-based theranostic agent using the barnase-barstar protein complex and studied its properties.

"Most of the currently used methods for chemically coupling biomolecules to nanoparticles have serious flaws," says lead author Victoria Shipunova, a researcher at MIPT's Nanobiotechnology Lab and a senior researcher at the Molecular Immunology Lab of the Institute of Bioorganic Chemistry. "The spatial orientation of the biomolecules is poorly controlled, and they encounter problems when binding to their targets. The density of the coupled molecules is fairly low, and the procedure is time-consuming."

"We developed a method based on the barnase-barstar protein pair that does not alter the spatial structure of the targeting molecules. Two further advantages are its high specificity and rapid coupling: It only takes several minutes for all modules to bind," she explains.

The researchers used silicon dioxide-coated particles as the carriers for their molecular complex. The primary targets of the biostructures described in the paper are cancer cells, identifiable by the HER2/neu oncomarker on their surface, shown as a red outgrowth in figure 2. HER2/neu is a protein responsible for cell growth and division and present in healthy cells. In cancer cells, however, this protein is in excess -- or overexpressed -- enabling them to grow and divide uncontrollably.

The researchers used a molecule from the class of designed ankyrin repeat proteins, or DARPins, as the targeting agent recognizing the HER2/neu protein. Shown as light blue bellflower-shaped structures in figures 1 and 2, DARPins are small and highly stable proteins capable of selectively binding to the target molecule. Besides a DARPin molecule, which recognizes cancer cells, the structure needs to incorporate a molecule capable of binding to the carrier particle's surface -- that is, to silicon dioxide. For this, the researchers used a silicon dioxide-binding peptide obtained by rational design at Macquarie University. As a result, they created the following structure: A nano- or microparticle is coated with silicon dioxide, to which the barnase-DARPin module is attached via the silicon dioxide-binding peptide fused with barstar (figure 1). Importantly, each of the elements involved can be altered or even replaced, modifying the properties of the overall structure. In a way, it is similar to a molecular kit of building blocks, which can be assembled in many ways, producing different therapeutic agents.

In effect, the researchers have created a universal assembly method, which allows a number of molecules with therapeutic and diagnostic potential to be easily combined, while preserving their spatial structure and properties.
-end-


Moscow Institute of Physics and Technology

Related Cancer Cells Articles:

Cancer cells send signals boosting survival and drug resistance in other cancer cells
Researchers at University of California San Diego School of Medicine report that cancer cells appear to communicate to other cancer cells, activating an internal mechanism that boosts resistance to common chemotherapies and promotes tumor survival.
A protein that stem cells require could be a target in killing breast cancer cells
Researchers have identified a protein that must be present in order for mammary stem cells to perform their normal functions.
Single gene encourages growth of intestinal stem cells, supporting 'niche' cells -- and cancer
A gene previously identified as critical for tumor growth in many human cancers also maintains intestinal stem cells and encourages the growth of cells that support them, according to results of a study led by Johns Hopkins researchers.
Prostate cancer cells grow with malfunction of cholesterol control in cells
Advanced prostate cancer and high blood cholesterol have long been known to be connected, but it has been a chicken-or-egg problem.
Immune therapy scientists discover distinct cells that block cancer-fighting immune cells
Princess Margaret Cancer Centre scientists have discovered a distinct cell population in tumours that inhibits the body's immune response to fight cancer.
New system developed that can switch on immune cells to attack cancer cells
Researchers have developed an artificial structure that mimics the cell membrane, which can switch on immune cells to attack and destroy a designated target.
Hybrid immune cells in early-stage lung cancer spur anti-tumor T cells to action
Researchers have identified a unique subset of these cells that exhibit hybrid characteristics of two immune cell types -- neutrophils and antigen-presenting cells -- in samples from early-stage human lung cancers.
New analytical technology to quantify anti-cancer drugs inside cancer cells
University of Oklahoma researchers will apply a new analytical technology that could ultimately provide a powerful tool for improved treatment of cancer patients in Oklahoma and beyond.
Sleep hormone helps breast cancer drug kill more cancer cells
Tiny bubbles filled with the sleep hormone melatonin can make breast cancer treatment more effective, which means people need a lower dose, giving them less severe side effects.
Breast cancer tumor-initiating cells use mTOR signaling to recruit suppressor cells to promote tumor
Baylor College of Medicine researchers report a new mechanism that helps cancer cells engage myeloid-derived suppressor cells.

Related Cancer Cells Reading:

One Renegade Cell: How Cancer Begins (Science Masters Series)
by Robert A. Weinberg (Author)

Cancer research has reached a major turning point, and no one is better qualified to explain the past two deacades' dramatic leaps forward in understanding this disease than world-renowned molecular biologist Robert Weinberg, director of the Oncology Research Laboratory at the Whitehead Institute in Cambridge, Massachusetts. In One Renegade Cell, Weinberg presents a state-of-the-art account of how cancer begins and how, one day, it will be cured. View Details


Essential Oils And Cancer: How To Effectively Use The Right Essential Oils To Confuse And Kill Cancer Cells
by Nancy Dennett Ducharme (Author)

Essential oils have been used for centuries to help support the immune system and bring the body back to health. This first book in the Essential Oils And Cancer series shows step by step exactly how to use essential oils to fight cancer. Learn how to prepare and use the compounds in two specific plant species to attack and destroy abnormal cells and cell mutations that have grown out of control. Learn which combinations of essential oils to use with breast cancer, bone cancer, lung cancer, skin cancer, prostate cancer, and other cancers according to latest scientific research. View Details


Cancer: The Outlaw Cell
by Richard LaFond (Editor)

We live in an era in which scientific information grows by the day and is so specialized that no one person can possibly absorb and kept abreast of the literature. Substantial developments in science and medicine, powered by developing technologies such as genetic sequencing, proteomics, and nanobiology, have driven cancer research forward, and a review of where we are now is desperately needed.

Cancer: The Outlaw Cell is a collection of twenty-five focused chapters written by leading researchers at the forefront of cancer research. Authors present the current state of... View Details


Cancer: Basic Science and Clinical Aspects
by Craig A. Almeida (Author), Sheila A. Barry (Author)

“... Useful background information is displayed in blue boxes, and good use is made of numerous tables and diagrams... a useful book for the undergraduate medical or allied health professional...” –Oncology News, May/June 2010


This forward looking cancer biology book appeals to a wide ranging audience. Introductory chapters that provide the molecular, cellular, and genetic information needed to comprehend the material of the subsequent chapters bring unprepared students up to speed for the rest of the book and serve as a useful refresher for those with previous biology... View Details


How To Kill Cancer Cells: Make Your Body Healthy Now
by Natalie Mitchell (Author)

Natalie Mitchell’s Amazon Best Seller second book “How To Kill Cancer Cells” sets out clear guidelines for readers to create a bodily environment in which cancer cells cannot thrive. Everybody has cancer cells and with the medical technology available nowadays doctors can only diagnose cancer disease when people already have developed BILLIONS of active cancer cells in their body. While the information itself is easy to understand, the Author’s clear message is that we, as individuals, can control our susceptibility to Cancer, eliminate Cancer cells and prevent and avoid the disease... View Details


NCCN Guidelines for Patients®: Lung Cancer (Non-Small Cell Lung Cancer) 2018
by National Comprehensive Cancer Network® (NCCN®) (Author)

From the medical leaders of 27 leading cancer centers united under the National Comprehensive Cancer Network® (NCCN®), comes this essential guide to Lung Cancer (Non-Small Cell Lung Cancer). Adapted from clinical treatment guidelines used by physicians and oncology professionals around the world, these NCCN Guidelines for Patients® are packed with the latest information, treatment innovations, and resources. Each patient-friendly chapter prepares patients and caregivers to talk with their doctors and make treatment decisions. Let this authoritative handbook be your guide! Part 1 – Lung... View Details


Stem Cells For Dummies
by Lawrence S.B. Goldstein (Author), Meg Schneider (Author)

The first authoritative yet accessible guide to this controversial topic

Stem Cell Research For Dummies offers a balanced, plain-English look at this politically charged topic, cutting away the hype and presenting the facts clearly for you, free from debate. It explains what stem cells are and what they do, the legalities of harvesting them and using them in research, the latest research findings from the U.S. and abroad, and the prospects for medical stem cell therapies in the short and long term.

Explains the differences between adult stem cells and embryonic/umbilical... View Details


The Cancer Fighting Diet: Diet and Nutrition Strategies to Help Weaken Cancer Cells and Improve Treatment Results
by Dr. Johannes Coy Sc.D. (Author), Maren Franz (Author)

This book provides basic information about cancer, as well as detailed advice and a comprehensive diet plan to help fight a personal battle with cancer and significantly improve chances of a cure.

There are complex processes inside the human body and specific mechanisms that can lead to the development and spread of cancer cells. Understanding the causes for what is happening inside the body is the key to implementing the recommendations in this guide.

Using these recipes and nutritional strategies will cut dramatically down on sugar in order to deplete the strength and... View Details


A Beginner's Guide to Targeted Cancer Treatments
by Elaine Vickers (Author)

The accessible guide to the principles behind new, more targeted drug treatments for cancer

Written for anyone who encounters cancer patients, cancer data or cancer terminology, but have no more than a passing knowledge of cell biology. A Beginner's Guide to Targeted Cancer Treatments provides an understanding of how cancer works and the many new treatments available.

Using over 100 original illustrations, this accessible handbook covers the biology and mechanisms behind a huge range of targeted drug treatments, including many new immunotherapies. Dr Vickers... View Details


Cancer Stem Cells: Philosophy and Therapies
by Lucie Laplane (Author)

An innovative theory proposes a new therapeutic strategy to break the stalemate in the war on cancer. It is called cancer stem cell (CSC) theory, and Lucie Laplane offers a comprehensive analysis, based on an original interdisciplinary approach that combines biology, biomedical history, and philosophy.

Rather than treat cancer by aggressively trying to eliminate all cancerous cells―with harmful side effects for patients―CSC theory suggests the possibility of targeting the CSCs, a small fraction of cells that lie at the root of cancers. CSCs are cancer cells that also have the... View Details

Best Science Podcasts 2018

We have hand picked the best science podcasts for 2018. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

The Person You Become
Over the course of our lives, we shed parts of our old selves, embrace new ones, and redefine who we are. This hour, TED speakers explore ideas about the experiences that shape the person we become. Guests include aerobatics pilot and public speaker Janine Shepherd, writers Roxane Gay and Taiye Selasi, activist Jackson Bird, and fashion executive Kaustav Dey.
Now Playing: Science for the People

#478 She Has Her Mother's Laugh
What does heredity really mean? Carl Zimmer would argue it's more than your genes along. In "She Has Her Mother’s Laugh: The Power, Perversions, and Potential of Heredity", Zimmer covers the history of genetics and what kinship and heredity really mean when we're discovering how to alter our own DNA, and, potentially, the DNA of our children.