Researchers from Case Western Reserve University School of Medicine in collaboration with researchers from Dartmouth Geisel School of Medicine and RWTH Aachen University (Germany) have adapted virus particles—that normally infect potatoes—to serve as cancer drug delivery devices for mice. But in a recent article published in Nano Letters, the team showed injecting the virus particles alongside chemotherapy drugs, instead of packing the drugs inside, may provide an even more potent benefit.
The researchers discovered injecting potato virus particles into melanoma tumor sites activates an anti-tumor immune system response. And simultaneously injecting the nanoscale plant virus particles and a chemotherapy drug—doxorubicin—into tumor sites further helps halt tumor progression in mice. But surprisingly, when the researchers created and injected combination nanoparticles, where the chemo drug is physically attached to the virus particles, there was not a significant added benefit.
The results are the first to show “vaccinating” mice with potato virus nanoparticles at a cancer site can generate an anti-tumor response. But the results also suggest more complex nanoparticles may not correspond to added therapeutic benefit.
“It’s attractive to want to create multifunctional nanoparticles that can ‘do it all,’” said Nicole F. Steinmetz, PhD, senior author on the study, George J. Picha Professor in Biomaterials, member of the Case Comprehensive Cancer Center, and Director of the Center for Bio-Nanotechnology at Case Western Reserve School of Medicine. “But this study shows significant therapeutic efficacy, including prolonging survival, requires a more step-wise approach. When the plant-based virus particles and the drugs were able to work on their own, we saw the greatest benefit.”
Wrote the authors, “While the nanomedicine field strives to design multifunctional nanoparticles that integrate several functions and therapeutic regimens into single nanoparticle – our data suggest a paradigm shift; some therapeutics may need to be administered separately to synergize and achieve most potent therapeutic outcome.”
Steinmetz and her team will next investigate mechanisms behind the potato virus particles’ anti-tumor effects. She plans to test whether co-administering the nanoparticles with different chemotherapy drugs can delay, or slow the progression of other cancers. Said Steinmetz, “Dual-pronged therapeutic approaches may be our best defense against certain cancers. And, virus-based nanoparticles like the ones in our study may be used to enhance efficacy of existing medications.”
This work was funded in part by a Research Scholar Award from the American Cancer Society (128319-RSG-15-144-01-CDD to N.F.S.), training grants from the National Institutes of Health (R25 CA148052 to K.L.L., T32 EB007509 to K.L.L., T32 GM007250 to A.A.M., TL1 TR000441 to A.A.M.), and a Case Western Reserve University (CWRU) Council to Advance Human Health (CAHH) Award (to N.F.S.).
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Founded in 1843, Case Western Reserve University School of Medicine is the largest medical research institution in Ohio and is among the nation's top medical schools for research funding from the National Institutes of Health. The School of Medicine is recognized throughout the international medical community for outstanding achievements in teaching. The School's innovative and pioneering Western Reserve2 curriculum interweaves four themes--research and scholarship, clinical mastery, leadership, and civic professionalism--to prepare students for the practice of evidence-based medicine in the rapidly changing health care environment of the 21st century. Nine Nobel Laureates have been affiliated with the School of Medicine.
Annually, the School of Medicine trains more than 800 MD and MD/PhD students and ranks in the top 25 among U.S. research-oriented medical schools as designated by U.S. News & World Report's"Guide to Graduate Education."
The School of Medicine is affiliated with University Hospitals Cleveland Medical Center, MetroHealth Medical Center, the Louis Stokes Cleveland Department of Veterans Affairs Medical Center, and the Cleveland Clinic, with which it established the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University in 2002. case.edu/medicine.
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