Hybrid molecule could be promising treatment against malignant cells
A novel hybrid molecule synthesized and developed by a team at New York University (NY, USA) shows promise as a drug delivery mechanism with potential anti-cancer applications.
Researchers from the New York University Tandon School of Engineering (NY, USA) have developed a novel hybrid molecule that could aid treatment of diseases such as breast cancer by ‘shipping’ cytotoxic chemotherapeutic agents to malignant cells. The protein/polymer-gold nanoparticle (P-GNP) composite are loaded with the drugs, transport them to malignant cells, and precisely dose these cells in a way that causes the least possible harm to the patient.
The novel molecule enhances small-molecule loading, sustained release and increased drug uptake in breast cancer cells, and is relatively simple to synthesize. Jin Kim Montclare developed the molecule in collaboration with colleagues at Brooklyn College and the City University of New York (both NY, USA), and she describes how these abilities make the P-GNP vehicle unique.
“The protein component has been exclusively developed in our lab; no one else has made such constructs,” Montclare explained. The polymers are able to self-assemble in a temperature-sensitive way, and exhibit the ability to encapsulate small molecules. The researchers tested the molecule in combination with the anti-inflammatory compound curcumin as the chemotherapy agent, against MCF-7 breast cancer cells. Compared to the polymer alone, the P-GNP hybrid had more than seven times the increase in curcumin binding, nearly twice the cellular uptake of curcumin and close to 50 percent slower release profile.
Given the challenge in delivering chemotherapy to its target, as these compounds tend to be hydrophobic, this is an important achievement. Generally, the more potent a chemotherapeutic agent, the more hydrophobic it is. "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," Montclare elaborated.
Montclare also discovered a way to easily build these hybrid molecules, without the high temperatures and pressures and complex chemistry the majority of the literature would suggest necessary. She is able to synthesize the molecule in one operation, utilizing histidine tags.
Montclare concluded that histine tags 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."
Montclare and colleagues’ next step is to observe the molecule’s efficacy by injecting it into mouse cancer molecules, with human testing still a distant ambition.
Min D, Frezzo JA, Sharma E et al. Engineered Protein Polymer-Gold Nanoparticle Hybrid Materials for Small Molecule Delivery. J. Nanomed. Nanotechnol. 7(356) (2016); http://engineering.nyu.edu/press-release/2016/04/01/nyu-tandon-researcher-synthesizes-hybrid-molecule-delivers-blow-malignant