QN-247: A Highly Potent and Differentiated Anti-Cancer Drug Candidate

QN-247, formerly referred to as ALAN (Aptamer Linked Anti Nucleolin), is an aptamer-based investigational drug candidate currently under development and evaluation with the potential to treat a variety of different cancer types, including liquid and solid tumors. QN-247 is a DNA aptamer conjugated to a gold nanoparticle, which potentially gives it dramatically increased potency and versatility. Preclinical studies in breast cancer with QN-247 showed significant cell inhibition activity. Beyond QN-247, linking an aptamer to a gold nanoparticle has potential applications for enhanced radiation therapy, tumor imaging, and the delivery of other anti-cancer compounds directly to tumor cells.

Aptamer-Gold Conjugates Target Nucleolin on Surface of Cancer Cells

Originally developed in a collaboration between Qualigen Therapeutics and the University of Louisville, QN-247 is a formulation containing a DNA aptamer conjugated to a gold nanoparticle (GNP). QN-247 inhibits nucleolin, a key multi-functional regulatory protein that is overexpressed in cancer cells, thus influencing their proliferation, survival, and metastasis.

Aptamers: Aptamers are single-stranded nucleic acid oligonucleotides which bind to their targets with high specificity and affinity. Owing to their excellent properties compared to conventional antibodies, notably their smaller physical size and lower immunogenicity and toxicity, aptamers have recently emerged as a new class of agents to deliver therapeutic drugs to cancer cells by targeting specific cancer-associated hallmarks. Aptamers can also be structurally modified to enable conjugation with other agents, such as nanomaterials like GNPs, thus extending their applications for cancer therapy.1

GNPs: Modern medicine makes routine, conventional use of gold and has developed more advanced applications by recent breakthroughs in nanoscale manufacturing. Gold can be functionalized further because of the presence of thiol and amine groups, allowing for the conjugation of various functional groups such as aptamers. It has been shown that colloidal gold nanoparticles can absorb light at specific wavelengths, resulting in photoacoustic and photothermal properties, making them potentially useful for cancer treatments. By manufacturing gold in a nanoscale format, it is possible to passively distribute the material through the body, where it can localize in tumors (which are characterized by leaky blood vessels) and be safely excreted through the urinary system.2

Potential Advantages

  1. QN-247 Inhibits growth across a range of in-vitro cancer cell lines
  2. Biodistribution studies show tumor-selective accumulation of QN-247 versus normal tissue
  3. Potential to dramatically increase potency when gold nanoparticle is conjugated versus DNA nucleolin targeting agent alone

Posters & Publications

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  1. Aptamers: A promising chemical antibody for cancer therapy. Oncotarget. 2016 Mar 22; 7(12): 13446–13463. Published online 2016 Feb 3. doi: 10.18632/oncotarget.7178
  2. Gold Nanoparticles for Photothermal Cancer Therapy. Front. Chem., 05 April 2019. https://doi.org/10.3389/fchem.2019.00167