Shows promise for breast cancer Rx, the protein/polymer-gold nanoparticle composite, besides being easy to synthesize, can load up with cytoxotic drugs, carry them to malignant cells, and unload them where they can do the most damage with the least amount of harm to the patient.
The hybrid molecule enhances small-molecule loading, sustained release, and increased uptake in breast cancer cells. A/Prof Montclare explained that these abilities make the P-GNP vehicle unique among hybrids. “The protein component has been exclusively developed in our lab; no one else has made such constructs,” she said. These protein polymers possess the unique ability to self-assemble in a temperature-sensitive manner while also exhibiting the ability to encapsulate small molecules.
The team performed tests with in vitro samples of the MCF-7 breast cancer cell line, using the anti-inflammatory compound curcumin, shown experimentally to inhibit cancer cell growth when applied directly to a tumor, as the chemotherapy agent. When compared to the protein polymers alone, the P-GNP hybrid demonstrated a greater than 7X increase in curcumin binding, a nearly 50 slower release profile, and more than 3X increase in cellular uptake of curcumin.
This is an important achievement, given the difficulty in delivering chemotherapeutic compounds to their targets because such agents tend to be hydrophobic. “The P-GNPs are able to solubilize the hydrophobic small molecule through both the protein domain itself, and the gold nanoparticles. Thus, P-GNP can carry higher payloads, enabling it to deliver more drug,” she said.
She also found an easier way to build these hybrid molecules. Montclare is able to synthesize P-GNP in one operation thanks to histidine tags, which, she said, are “responsible for ‘templating’ the GNPs, making the synthesis a possibility under ambient temperature and pressure. So we do it all at once because the protein itself crystallizes the gold right from a solution of gold salts to generate GNP right on the end of the protein polymer.”
The next step is to observe efficacy by injecting P-GNP complexes directly into a variety of mouse cancer models. Montclare said human testing of P-GNP is still years away. http://engineering.nyu.edu/press-release/2016/04/01/nyu-tandon-researcher-synthesizes-hybrid-molecule-delivers-blow-malignant
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