Researchers program biomaterials with logic gates that release therapeutics in response to environmental triggers

Left-to-right: Barry Badeau, Christopher Arakawa, Jared Shadish, Cole DeForest.
CREDIT
Dennis Wise/University of Washington
Researchers program biomaterials with ‘logic gates’ that release therapeutics in response to environmental triggers

Drug treatments can save lives, but sometimes they also carry unintended costs. After all, the same therapeutics that target pathogens and tumors can also harm healthy cells.

To reduce this collateral damage, scientists have long sought specificity in drug delivery systems: A package that can encase a therapeutic and will not disgorge its toxic cargo until it reaches the site of treatment — be it a tumor, a diseased organ or a site of infection.

In a paper published Jan. 15 in the journal Nature Chemistry, scientists at the University of Washington announced that they have built and tested a new biomaterial-based delivery system — known as a hydrogel — that will encase a desired cargo and dissolve to release its freight only when specific physiological conditions are met. These environmental cues could include the presence of an enzyme or even the acidic conditions that could be found in a tumor microenvironment. Critically, the triggers that cause dissolution of the hydrogel can be switched out easily in the synthesis process, allowing researchers to create many different packages that open up in response to unique combinations of environmental cues.

The team, led by UW chemical engineering assistant professor Cole DeForest, designed this hydrogel using the same principles behind simple mathematical logic statements — those at the heart of basic programming commands in computer science.

“The modular strategy that we have developed permits biomaterials to act like autonomous computers,” said DeForest, who is also a member of both the Institute for Stem Cell & Regenerative Medicine and the Molecular Engineering & Sciences Institute. “These hydrogels can be programmed to perform complex computations based on inputs provided exclusively by their local environment. Such advanced logic-based operations are unprecedented, and should yield exciting new directions in precision medicine.”

Hydrogels are more than 90 percent water; the remainder consists of networks of biochemical polymers. Hydrogels can be engineered to ferry a variety of therapeutics, such as pharmaceutical products, special cells or signaling molecules, for purposes including drug delivery or even 3-D tissue engineering for transplantation into patients.

The key to the team’s innovation lies in the way the hydrogels were synthesized. When researchers assembled the polymer network that comprises the biomaterial, they incorporated chemical “cross-link” gates that are designed to open and release the hydrogel’s contents in response to user-specified cues — much like how the locked gates in a fence will only “respond,” or open with a specific set of keys.

“Our ‘gates’ consist of chemical chains that could — for example — be cleaved only by an enzyme that is uniquely produced in certain tissues of the body; or be opened only in response to a particular temperature or specific acidic conditions,” said DeForest. “With this specificity, we realized we could more generally design hydrogels with gates that would open if only certain chemical conditions — or logic statements — were met.”

DeForest and his team built these hydrogel gates using simple principles of Boolean logic, which centers on inputs to simple binary commands: “YES,” “AND” or “OR.” The researchers started out by building three types of hydrogels, each with a different “YES” gate. They would only open and release their test cargo — fluorescent dye molecules — in response to their specific environmental cue.

One of the “YES” gates they designed is a short peptide — one of the constituent parts of cellular proteins. This peptide gate can be cleaved by an enzyme known as matrix metalloprotease (MMP). If MMP is absent, the gate and hydrogel remain intact. But if the enzyme is present in a cell or tissue, then MMP will slice the peptide gate and the hydrogel will burst open, releasing its contents. A second “YES” gate that the researchers designed consists of a synthetic chemical group called an ortho-nitrobenzyl ester (oNB). This chemical gate is immune to MMP, but it can be cleaved by light. A third “YES” gate contains a disulfide bond, which breaks upon reaction with chemical reductants but not in response to light or MMP. A hydrogel containing one of these types of “YES” gates is essentially “programmed” to respond to its physiological surroundings using the Boolean logic of its cross-link gate. A hydrogel with an oNB gate, for example, will open and release its contents in the presence of light, but not any of the other cues like the MMP enzyme or a chemically reductive environment.

They also created and tested hydrogels with multiple types of “YES” gates, essentially creating hydrogels with gates that would open and release their cargo in response to multiple combinations of environmental cues, not just one cue: light AND enzyme; reductant OR light; enzyme AND light AND reductant. Hydrogels with these more complex types of gates could still carry cargo, either fluorescent dyes or living cells, and release it only in response to the particular gate’s unique combination of environmental triggers.

The team even tested how well a hydrogel with an “AND” gate — reductant and the enzyme MMP — could ferry the chemotherapy drug doxorubicin. The doxorubicin-containing hydrogel was mixed with cultures of tumor-derived HeLa cells, which doxorubicin should kill easily. But the hydrogel remained intact, and the HeLa cancer cells remained alive unless the researchers added both triggers for the “AND” gate: MMP and reductant. One cue alone was insufficient to cause HeLa cell demise.

See Also
Photo by L. Brian Stauffer University of Illinois kinesiology and community health professor Marni Boppart studies the mechanisms that enable muscles to recover and grow stronger after exercise.

DeForest and his team are building on these results to pursue even more complex gates. After all, specificity is the goal, both in medicine and tissue engineering.

“Our hope is that, by applying Boolean principles to hydrogel design, we can create a class of truly smart therapeutic delivery systems and tissue engineering tools with ever-greater specificity for organs, tissues or even disease states such as tumor environments,” said DeForest. “Using these design principles, the only limits could be our imagination.”

Learn more: Biomaterials with ‘logic gates’ release therapeutics in response to environmental triggers

 

The Latest on: Biomaterials with logic gates
[google_news title=”” keyword=”biomaterials with logic gates” num_posts=”10″ blurb_length=”0″ show_thumb=”left”]
  • Best free Logic Gate simulator software for Windows PC
    on January 5, 2023 at 11:59 pm

    Logic Gates are among the important components of a circuit. All the logical operations required to perform a particular task in an electronic circuit are carried by these logic gates. If you are ...

  • logic gates
    on December 29, 2022 at 4:00 pm

    How well do you know your logic gates? For their final submission for STEM Projects class, [BKriet] gamified the situation using a Raspberry Pi Pico, some blinkenlights, and a not-insignificant ...

  • Bill Gates and Melinda French Gates' Relationship Timeline
    on October 5, 2022 at 10:41 am

    Bill Gates and Melinda French Gates were married for 27 years and welcomed three children before divorcing in 2021 After nearly three decades of marriage, Bill Gates and Melinda French Gates ...

  • Biomaterials and Tissue Engineering
    on June 17, 2022 at 4:51 am

    Nanoscale structure-property relationships of biological materials, genetic and molecular origins of soft joint tissue diseases, biomaterials under extreme conditions, coupling between ...

  • Biomaterials and Tissue Engineering
    on August 18, 2020 at 2:15 pm

    Biomaterials are being developed in response to clinical need. Research includes work on new biomaterials for cell culture and tissue engineering, drug release, transfection, prosthetics and enhanced ...

  • Systems: Sources and functions of components - Eduqas
    on July 25, 2020 at 9:11 pm

    Logic gates can be combined in many ways. To work out what the final output will be, the truth tables must be used to track the outputs and inputs along the combination of logic gates, like ...

  • Biomaterials Engineering
    on March 31, 2018 at 11:16 pm

    Alfred University offers an MS degree in Biomaterials Engineering (BME) designed for students who wish to study materials for medical applications. Our BME graduates are well prepared to enter the ...

  • Logic Gates Information
    on February 11, 2018 at 6:42 am

    Logic gates are circuits with electronically controlled switches that combine digital signals according to Boolean algebra. In binary math, bits have only two possible values: 0 (off, false) and 1 (on ...

  • Make Logic Gates Out Of (Almost) Anything
    on January 2, 2017 at 11:11 pm

    Logic gates are the bricks and mortar of digital electronics, implementing a logical operation on one or more binary inputs to produce a single output. These operations are what make all ...

  • Food and Biomaterials Production
    on June 21, 2015 at 11:04 pm

    The Food and Biomaterials Production cluster includes occupations that focus on the production of commodities used as food or biomaterials. This also includes occupations in forest production, ...

via Google News and Bing News

What's Your Reaction?
Don't Like it!
0
I Like it!
0
Scroll To Top