Nav: Home

Micron-sized hydrogel cubes show highly efficient delivery of a potent anti-cancer drug

June 28, 2017

BIRMINGHAM, Ala. - Many potent anti-cancer drugs have major drawbacks -- they fail to mix with water, which means they will have a limited solubility in blood, and they lack selectivity to cancer cells.

Researchers at the University of Alabama at Birmingham and Texas Tech University Health Sciences Center have developed micro-cubes that can sponge up a hydrophobic anti-cancer drug and deliver it to cancer cells. Tissue culture tests show these tiny, porous cubes, loaded with the hydrophobic drug, are more potent against liver cancer cells and less harmful to normal liver cells, compared to the drug alone.

"We believe that our novel drug-delivery platform for the highly potent anti-cancer drug BA-TPQ provides a facile method for encapsulation of hydrophobic drugs and can facilitate enhanced efficacy for liver cancer therapy," the researchers said in an Acta Biomaterialia paper. The liver cancer, hepatocellular carcinoma, is the third-leading cause of cancer death worldwide, and the need for new curative compounds that can improve patient outcomes is urgent.

BA-TPQ is an iminoquinone derivative, and it is one of the most potent analogs of natural anti-cancer compounds discovered in the Philippine sponge Zyzzya fuliginosa.

BA-TPQ has high potency against human breast and prostate cancer cell lines, but its use has been limited by poor solubility, low bioavailability and undesirable toxicity. The goals for a delivery system are improved anti-cancer efficacy and reduction of side effects.

The research was led by co-senior authors Eugenia Kharlampieva, Ph.D., and Sadanandan E. Velu, Ph.D., both associate professors of chemistry in the UAB College of Arts and Sciences, and Ruiwen Zhang, M.D., Ph.D., professor in the School of Pharmacy, Texas Tech University Health Sciences Center.

The 2-micrometer cubes are made of layers of cross-linked poly(methacrylic acid) formed on a porous scaffold that is then removed. Poly(methacrylic acid) is non-toxic and is biocompatible for clinical use.

The hydrogel carriers filled with BA-TPQ are soft but can retain their cubic shape, and the cubic shape aids uptake by cancer cells. A higher redox potential, such as that found inside cells, facilitates dissolution of the tiny cubes and release of the BA-TPQ drug. Furthermore, cancer cells often have higher redox potentials than normal cells.

The drug-loaded cubes can be freeze-dried and then resuspended in solution without losing their shape, which may allow long-term storage of the cubes as powder.

Besides the selectivity of the BA-TPQ-hydogel cubes for the two lines of liver cancer cells tested in comparison with normal liver cells, the drug-loaded cubes affected expression of genes involved in cancer promotion or prevention.

For one line of liver cancer cells, encapsulating BA-TPQ within the hydrogel cubes significantly amplified the potency of BA-TPQ to decrease the expression of the oncogenic protein, MDM2, and increase the expression of the tumor suppressor, p53, and the cell proliferation suppressor, p21. Tests in another line of liver cancer cells showed that the enhanced inhibition of MDM2 by BA-TPQ-hydrogel cubes was independent of p53 status, which means that for cancer cells with p53 mutation, commonly occurring in hepatocarcinoma cells and promoting tumorigenesis, the BA-TPQ-hydrogel cubes may be a successful candidate for anti-tumor treatment.

While hydrogel cubes loaded with BA-TPQ can be delivered intravenously, the researchers also showed they also have potential to be taken orally. The drug-loaded cubes retained their integrity when exposed to a strong acid environment of pH 2, mimicking stomach conditions, and they showed increased permeability across an epithelial cell monolayer, compared to drug alone, which indicates a better chance of absorption for the drug-loaded hydrogel cubes from the gut.
-end-
Co-authors of the paper, "Highly efficient delivery of potent anticancer iminoquinone derivative by multilayer hydrogel cubes," are Bing Xue, Wei Wang, Jiang-Jiang Qin, Bhavitavya Nijampatnam, Srinivasan Murugesan and Veronika Kozlovskaya. Wang and Qin are in the School of Pharmacy, Texas Tech University Health Sciences Center; the other co-authors are in the UAB Department of Chemistry.

Co-senior authors Kharlampieva and Velu are members of the UAB Comprehensive Cancer Center, and Kharlampieva is a member of the UAB Center for Nanoscale Materials and Biointegration.

University of Alabama at Birmingham

Related Cancer Cells Articles:

Drug that keeps surface receptors on cancer cells makes them more visible to immune cells
A drug that is already clinically available for the treatment of nausea and psychosis, called prochlorperazine (PCZ), inhibits the internalization of receptors on the surface of tumor cells, thereby increasing the ability of anticancer antibodies to bind to the receptors and mount more effective immune responses.
Engineered bone marrow cells slow growth of prostate and pancreatic cancer cells
In experiments with mice, researchers at the Johns Hopkins Kimmel Cancer Center say they have slowed the growth of transplanted human prostate and pancreatic cancer cells by introducing bone marrow cells with a specific gene deletion to induce a novel immune response.
First phase i clinical trial of CRISPR-edited cells for cancer shows cells safe and durable
Following the first US test of CRISPR gene editing in patients with advanced cancer, researchers report these patients experienced no negative side effects and that the engineered T cells persisted in their bodies -- for months.
Zika virus' key into brain cells ID'd, leveraged to block infection and kill cancer cells
Two different UC San Diego research teams identified the same molecule -- αvβ5 integrin -- as Zika virus' key to brain cell entry.
Plant-derived SVC112 hits cancer stem cells, leaves healthy cells alone
Study shows Colorado drug SVC112 stops production of proteins that cancer stem cells need to survive and grow.
Changes in the metabolism of normal cells promotes the metastasis of ovarian cancer cells
A systematic examination of the tumor and the tissue surrounding it -- particularly normal cells in that tissue, called fibroblasts -- has revealed a new treatment target that could potentially prevent the rapid dissemination and poor prognosis associated with high-grade serous carcinoma (HGSC), a tumor type that primarily originates in the fallopian tubes or ovaries and spreads throughout the abdominal cavity.
The development of brain stem cells into new nerve cells and why this can lead to cancer
Stem cells are true Jacks-of-all-trades of our bodies, as they can turn into the many different cell types of all organs.
White blood cells related to allergies may also be harnessed to destroy cancer cells
A new Tel Aviv University study finds that white blood cells which are responsible for chronic asthma and modern allergies may be used to eliminate malignant colon cancer cells.
Conversion of breast cancer cells into fat cells impedes the formation of metastases
An innovative combination therapy can force malignant breast cancer cells to turn into fat cells.
Breast cancer cells in mice tricked into turning into fat cells
As cancer cells respond to cues in their microenvironment, they can enter a highly plastic state in which they are susceptible to transdifferentiation into a different type of cell.
More Cancer Cells News and Cancer Cells Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Climate Mindset
In the past few months, human beings have come together to fight a global threat. This hour, TED speakers explore how our response can be the catalyst to fight another global crisis: climate change. Guests include political strategist Tom Rivett-Carnac, diplomat Christiana Figueres, climate justice activist Xiye Bastida, and writer, illustrator, and artist Oliver Jeffers.
Now Playing: Science for the People

#562 Superbug to Bedside
By now we're all good and scared about antibiotic resistance, one of the many things coming to get us all. But there's good news, sort of. News antibiotics are coming out! How do they get tested? What does that kind of a trial look like and how does it happen? Host Bethany Brookeshire talks with Matt McCarthy, author of "Superbugs: The Race to Stop an Epidemic", about the ins and outs of testing a new antibiotic in the hospital.
Now Playing: Radiolab

Speedy Beet
There are few musical moments more well-worn than the first four notes of Beethoven's Fifth Symphony. But in this short, we find out that Beethoven might have made a last-ditch effort to keep his music from ever feeling familiar, to keep pushing his listeners to a kind of psychological limit. Big thanks to our Brooklyn Philharmonic musicians: Deborah Buck and Suzy Perelman on violin, Arash Amini on cello, and Ah Ling Neu on viola. And check out The First Four Notes, Matthew Guerrieri's book on Beethoven's Fifth. Support Radiolab today at Radiolab.org/donate.