A ligand-protease fusion peptide that cuts through the tumor stromal barrier and provides enhanced tumor targeting and delivery efficiency for therapeutic agents.
- The protease activity of the fusion peptide enables breaking of the stromal matrix and allows migration into stroma-rich tumor tissues.
- Can be attached to nanoparticles or other imaging and drug delivery carriers for the enhanced tumor targeting and efficient therapeutic delivery
- By digesting the surrounding extracellular matrix this fusion peptide improves intratumoral distribution of the therapeutics to which it is conjugated.
There has been a recent surge in technologies that focus on the delivery of chemotherapeutic molecules to tumor cells for difficult to treat cancers. Because some compounds are unable to be delivered via traditional oral or injectable methods, this strategy has the potential to give new life to promising therapeutics. As such, drug delivery technologies are expected to continue to grow at a fast pace.
Delivering chemotherapeutics effectively and efficiently to a tumor is a major hurdle of cancer treatment. To get around metabolic and solubility challenges drugs are often given at high doses which leads to many side effects. Specifically directing drugs or imaging agents to tumors using targeted nanoparticle-drug conjugates is a strategy used to overcome many of these problems but additional delivery challenges remain. The key remaining challenge lies in the tumor’s dense extracellular matrix or stromal barrier which surrounds the tumor cells and limits drug penetration into the tumor. Emory researchers have developed a nanoparticle conjugated to a ligand-protease fusion peptide that is able to penetrate the stromal barrier. This fusion protein contains a matrix metallopeptidase protease that chews through the extracellular matrix which enhances tumor penetrance and a targeting molecule that specifically targets tumor cells. In fact, when this fusion protein is linked to a nanoparticle, it accumulates in tumors in vivo to a greater extent than a nanoparticle to the targeting molecule alone in a mouse tumor model. Such a fusion targeting ligand can be used alone to directly conjugate with therapeutic agents, or conjugated to drug carriers, such as nanoparticle drug carriers for targeted delivery into tumors.
Nanoparticles conjugated to the ligand-protease fusion peptide have been validated in rodent cancer models as well as human tumors grafted in immune deficient mice.
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