Cancer-Killing Nanodaisies

NC State researchers have developed a potential new weapon in the fight against cancer: a daisy-shaped drug carrier that’s many thousands of times smaller than the period at the end of this sentence.

Once injected into the bloodstream, millions of these “nanodaisies” sneak inside cancer cells and release a cocktail of drugs to destroy them from within. The approach is more precise than conventional methods, and it may also prove more effective. By ensuring anti-cancer drugs reach their target in controlled, coordinated doses, nanodaisies could cut down on the side effects of traditional chemotherapy.

“By using one nanocarrier to contain two different drugs, we can potentially reduce their dose and toxicity,” said Dr. Zhen Gu, assistant professor in the Joint Department of Biomedical Engineering at NC State and UNC-Chapel Hill. “And meanwhile their anti-cancer efficacy is enhanced.”

The nanocarriers are made from a polymer called polyethylene glycol (PEG), to which researchers attach the cancer-killing drug camptothecin (CPT) like bunches of grapes on a vine. A second drug, doxorubicin, also floats in solution around the PEG.

Both drugs are hydrophobic, meaning they dislike water and shy away from it. PEG, though, is hydrophilic: When exposed to water it stretches out to maximize contact, while the T-shaped joints that hold the CPT tug in the opposite direction and fold inward. The anti-cancer drugs thus end up tucked into a protective shell of PEG. The resulting nanocarrier is shaped like a flower — hence the term “nanodaisy.”

The idea came from thinking actively about folding proteins in nature,” noted Gu, referring to the way amino acids can assemble themselves into thousands of different shapes. “It’s a sort of bio-inspired design.”

Dr. Zhen Gu of NC State holds up a red solution from his "nanodaisies" cancer research.
Dr. Zhen Gu, assistant professor in the Joint Department of Biomedical Engineering, holds up samples from his “nanodaisies” research.

Once folded, the nanodaisies are then injected into the bloodstream and absorbed by unwitting cancer cells, which are porous enough to let them in. The nanodaisies’ outer shells of PEG protect their payload of drugs and keep them from prematurely leaking.

The design of the nanodaisy also ensures that the two cancer drugs release at complementary speeds as their carrier comes apart inside the cancer cell. Each drug inhibits different enzymes in the cell, and they work in tandem to prevent or delay the development of drug resistance.

The result is that the drugs launch an attack on cancer that’s more closely coordinated and tightly targeted than traditional drug cocktails.

So far, in vivo testing in mice has shown that this approach produces significant accumulation of drugs in tumor sites instead of healthy organs. Gu noted that in vitro testing had also demonstrated the potential of nanodaisies to effectively target different kinds of cancer.

It’s shown a broad killing effect for a variety of cancer cell lines, including leukemia, breast and lung cancers,” he said.

Gu has led other research that has yielded a bio-inspired “cocoon” that tricks cells into consuming anti-cancer drugs and an injectable nano-network that controls blood sugar levels in diabetics. He is supported by faculty, staff and Ph.D. students in the Joint Department of Biomedical Engineering, a partnership between NC State and UNC-Chapel Hill that tackles urgent biomedical problems.

The next step for nanodaisies is preclinical testing to determine whether they might be ready to fight cancer in humans.

For Gu, that prospect has personal significance: His father was diagnosed with cancer when Gu was still in the womb. When friends and family came to console Gu’s mother, she told them that the baby she was carrying might one day help to treat cancer.

“I don’t want to say it’s a mission, but it is a passion that drives me,” Gu explained. “Before I came to the U.S., I did research on conducting plastics for electronic devices. When I moved into the cancer treatments with nanotechnology, that’s when my mum became really excited about my work.”

10 responses on “Cancer-Killing Nanodaisies

  1. ARNWESHA JANA says:

    Your work on cancer cell killing nanodaisies is really fabulous and it is explained in such a lucid manner that it really intrigued me. I opened the university site for the sake of my brother’s admission but could not help myself reading from your research. I myself have completed my Bachelors of Technology in Biotechnology in 2010 and tried in couple of US universities for pursuing higher studies but did not get financial assistance so had to give up my hope of pursuing a research career in the field of cancer treatments. The reason that moved you to cancer research is really touching and inspiring. I was also motivated in a bit same way when I lost my closest relative, my grandmother because of renal carcinoma at the age of 9 yrs. I even lost my grandfather who died even before I was born because of lung carcinoma. I really wanted to work in this field and with that desire I completed my undergrads in Biotechnology and also couple of summer internships. However I consider myself ill-fated for not being able to pursue my dream due to lack of opportunities.To support my family currently,I am working in a stem cell bank based in Singapore as a Sr. Executive- Quality Control.However, your work and life really inspired me and rekindled newer hopes in me. Maybe its never too late to live your dreams and I believe Prof. Gu, life will give me that second opportunity to pursue my long nurtured dream career. I would really love to get interesting updates of your research regarding nanodaisies only if you find myself eligible enough to share with.

    1. Alastair Hadden says:

      Hi, Arnwesha.

      Thank you for your kind words and for sharing your story. If you want to learn more about the work Dr. Gu is doing, you can visit his “Gu Group” site here. You can also use our tagging system to stay on stop of cancer research news at NC State; if you follow this link, it will take you to a list of all the stories we’ve run to date that involve cancer research.

      Good luck to you (and your brother)!

  2. Ted Bogart says:

    What keeps the nanodaisies out of non-cancer cells? Are they less porous?

  3. Naqi Agha says:

    Its Great to know about this “Nanodaisies” thing.
    I hope it gets soon in the treatment stage, cause currently my mother is suffering from stage 4 cancer. The doctors are giving absolutely no hope. Saying its a rare cancer type, “Cervical Cancer” in her lower body.

    We are deeply depressed & hoping for a Miracle from Allah.

    Anyways, Wish you guys all the Best! May you succeed in all of its best outcomes. :)

  4. Alastair Hadden says:

    Hi, Ted.

    Yes, as I understand it, cancer cells tend to be more porous than healthy cells (because they grow quicker). They also have poor lymphatic drainage, so nanoparticles like Dr. Gu’s “nanodaisies” stay within the cells longer, giving the drugs they carry a chance to do their work.

    Attacking cancer cells while sparing normal tissue has always been a major problem for cancer treatment. “Nanodaisies” offer one potential way to thread that needle.

  5. Justine says:

    Joined Dr. Gu’s seminar last month. He is really AWESOME!!! NC State needs more professors like Dr. Gu!

  6. Dane says:

    Shouts out to Dennis, the unmentioned guy in the picture. Keep on grinding!

  7. Yanqi says:

    Dr. Gu is really full of ideas. His inspiration comes from the relevant knowledge, nature and even his wife’s cooking. I believe that every crazy idea is a great opportunity to make exciting new discoveries through research.

  8. Jennifer says:

    Great article. Dr. Gu is my favorite professor at NC State. His class is always full of fun. Very Intelligent!

  9. Phyllis Moore-DeShazo says:

    Hello, Dr. Gu. I opened the site to log onto the internet while my daughter is attenfing the MSEN Program at NC State. There was the link to your groundbreaking research. I pray you are able to find a cure which effectively works on humans. This is also dear to my heart as my Mom died of colon cancer and my uncle hss been diagnosed with prostate cancer earlier this year. If you are seeking candidates for your preclinical testing, please contact me by email. Please continue your work as there are many who need a cure. May God continue to bless your hard work!

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