Posted in | Nanomedicine | Nanomaterials

Specialized Nucleic Acid-Based Nanostructures Could Be Used to Target Cancer Cells

Over a century ago, German Nobel laureate Paul Ehrlich popularized the “magic bullet” concept - a technique that clinicians might in the future use to target invading microbes without damaging other parts of the body. Although chemotherapies have been very useful as targeted treatments for cancer, undesirable side effects still trouble patients. Currently, scientists at the University of Missouri have shown that dedicated nucleic acid-based nanostructures could be used to target cancer cells while sidestepping normal cells.

David Porciani and his team demonstrated that specialized nucleic acid-based nanostructures could be used to target cancer cells while bypassing normal cells. (Image credit: Erica Overfelt, Bond Life Sciences Center)

Most of the therapeutic drugs are not able to discriminate the cancer cells from healthy cells. They are killing both cell populations (healthy and malignant), and the treatment can have harsher side effects than the cancer itself in the short term. We are developing ‘smart’ molecules that can bind with receptors that are found on the surface of cancer cells, thus representing a cancer signature. The idea is to use these smart molecules as vehicles to deliver chemotherapeutic drugs or diagnostics.

David Porciani, Postdoctoral Fellow, MU Bond Life Sciences Center

Employing a molecular process that imitates an extremely-accelerated form of natural evolution, Porciani and his team looked for nucleic acid ligands, or aptamers. Owing to their 3D structures, aptamers can be trained to bind to specific target molecules with high affinity and selectivity. When the target is a cancer-associated receptor, these aptamers can be used as molecular tools to recognize definitely diseased cells.

The researchers then “loaded” the aptamers with large, fluorescent RNAs generating nucleic-acid nanostructures.  Upon incubation with target cancer and non-target cells, only malignant cells were illuminated by the nanostructure revealing that the structures had properly bonded with their planned targets.

Next steps for our studies are to prove that these aptamers can be loaded with therapeutic molecules that specifically target and treat cancer cells leaving normal tissues untouched. While aptamers have been proven in the past as tools to deliver small drugs, our method paves the way to deliver even larger and potentially more powerful RNA-based drugs possibly creating that ‘magic bullet’ that Erhlich described in the last century.

David Porciani, Postdoctoral Fellow, MU Bond Life Sciences Center

This research showcases the power of translational precision medicine and the potential of the proposed Translational Precision Medicine Complex (TPMC) at the University of Missouri. The TPMC will invite together industry partners, multiple schools and colleges on campus, and the state and the federal government to enable precision and individualized medicine. Scientific progress accomplished at MU will be effectively converted into new devices, drugs, and treatments that deliver tailored patient care based on an individual’s genes, lifestyle, and environment, in due course enhancing health and comfort of people.

The research, “Modular cell-internalizing aptamer nanostructure enables targeted delivery of large functional RNAs in cancer cell lines,” was recently published in Nature Communications. Finance was provided by the National Institutes of Health (grants R01A107-4389 and R21AI21938).

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