Smart Nanoparticle Drug Delivery System Avoids Tumor-Protecting Obstacles

Once the iCluster particles accumulated at tumor sites, the intrinsic tumor extracellular acidity triggered the discharge of platinum prodrug-conjugated poly(amidoamine) dendrimers (diameter about five nanometers). Such a structural alteration promoted tumor penetration and cell internalization of the therapeutics. The internalized dendrimer prodrugs were further reduced intracellularly to release the drug cisplatin to kill the cancer cells.

The investigators reported in the March 28, 2016, online edition of the journal Proceedings of the National Academy of Sciences of the United States of America (PNAS) that they had validated the superior in vivo antitumor activities of the iCluster particles in several intractable mouse tumor models including poorly permeable pancreatic cancer, drug-resistant cancer, and metastatic cancer, which demonstrated their versatility and broad applicability.

"The negative side effects of cisplatin are a long-standing limitation for conventional chemotherapy," said contributing author Dr. Jinzhi Du, a postdoctoral researcher at Emory University. "In our study, the delivery system was able to improve tumor penetration to reach more cancer cells, as well as release the drugs specifically inside cancer cells through their size-transition property."

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Emory University
University of Science and Technology of China