Decrease the side effects of anticancer drugs


image: Schematic of cellulose nanocrystals capturing chemotherapeutic drugs with their charged and designed hairy extensions.
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Credit: Terasaki Institute for Biomedical Innovation

(LOS ANGELES) – Millions of people around the world are touched by cancer every year; over 39% of men and women are diagnosed with cancer in their lifetime. Chemotherapy is the most commonly used standard cancer treatment, and targeted administration of these drugs to the tumor site increases their effectiveness. However, too much medication can still circulate around the rest of the body and cause multiple side effects, including anemia, chronic infections, hair loss, jaundice, and fever.

A number of proposed methods have been attempted to remove unwanted chemotherapeutic drugs from the blood, particularly the widely used drug doxorubicin (DOX). But these methods resulted in insufficiently low DOX removal levels. Additional strategies that use electrically charged nanoparticles to bind DOX lose their effectiveness with exposure to charged molecules and proteins present in the blood, despite the addition of materials intended to protect the binding ability.

A collaborative team, which included scientists from Pennsylvania State University and the Terasaki Institute for Biomedical Innovation (TIBI), developed a method to address these challenges.

The method, described in Materials today Chemistry, is based on hairy cellulose nanocrystals – nanoparticles developed from the main component of plant cell walls and designed to have immense numbers of polymer chain “hairs” extending at each end. These bristles increase the potential drug uptake capacity of nanocrystals significantly beyond that of conventional nanoparticles and other materials.

To produce the hairy cellulose nanocrystals capable of capturing chemotherapy drugs, the researchers chemically treated the cellulose fibers found in softwood pulp and imparted a negative charge to the hair, making it stable against the charged molecules present in it. the blood. This corrects the problems encountered with conventional nanoparticles, whose charge can be rendered inert or reduced when exposed to blood, limiting the number of positively charged drug molecules to which they can bind in insignificant numbers.

The binding efficiency of nanocrystals was tested in human serum, the protein-rich liquid part of the blood. For every gram of hairy cellulose nanocrystals, more than 6000 milligrams of DOX were effectively removed from the serum. This represents an increase in DOX capture of two to three orders of magnitude compared to other methods currently available.

In addition, the capture of DOX occurred immediately after the addition of the nanocrystals and the nanocrystals had no toxic or harmful effect on red blood cells in whole blood or on cell growth of human umbilical cells.

Such a powerful means of drug uptake in the body can have a big impact on cancer treatment regimens, as doses can be raised to more effective levels without worrying about harmful side effects.

Principal investigator Amir Sheikhi, assistant professor of chemical and biomedical engineering at Penn State, offered an example of such an application. “For some organs, like the liver, chemotherapy can be given locally through catheters. If we could place a device based on the nanocrystals to capture excess drugs exiting the inferior vena cava of the liver, a major blood vessel, clinicians could potentially administer higher doses of chemotherapy to kill cancer faster without fear. damage healthy cells. Once the treatment is complete, the device can be removed.

In addition to removing excess chemotherapy drugs from the body, hairy cellulose nanocrystals could also target other unwanted substances such as toxins and addictive drugs to be eliminated from the body, and experiments have also shown the effectiveness of the drugs. nanocrystals in other separation applications, such as in the recovery of valuable items from electronic waste.

“What started out as a relatively simple concept has grown into a very efficient way of separating materials,” said Ali Khademhosseini, director and CEO of the Terasaki Institute for Biomedical Innovation. “This creates potential for large-scale and impactful biomedical and scientific applications of materials. “

The other authors are Sarah AE Young, Joy Muthami, Mica Pitcher, Petar Antovski, Patricia Wamea, Robert Denis Murphy, Reihaneh Haghniaz, Andrew Schmidt and Samuel Clark.

This work was supported by the National Institutes of Health (1R01EB024403-01).

PRESS CONTACT

Stewart Han, [email protected], +1 818-836-4393

Terasaki Institute for Biomedical Innovation

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The Terasaki Institute for Biomedical Innovation (terasaki.org) is a non-profit research organization who invents and promotes practical solutions that restore or improve the health of individuals. Research at the Terasaki Institute builds on scientific advancements in understanding what makes each person unique, from the macro-scale of human tissues to the micro-scale of genes, to create technological solutions to some of the problems. most urgent medical conditions of our time. We use innovative technological platforms to study human disease at the individual patient level by incorporating advanced computer and tissue engineering methods. The results of these studies are translated by our research teams into tailored diagnostic and therapeutic approaches encompassing custom materials, cells and implants with unique potential and wide applicability to a variety of diseases, disorders and injuries.

The Institute is made possible by an endowment from the late Dr. Paul I Terasaki, a pioneer in the field of organ transplant technology.


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