Advancements in Targeted Delivery of Therapeutic Proteins

Prof. Thai Thayumanavan

“What our team has done,” explains Khushboo Singh, a graduate student in the chemistry department and one of the study’s lead authors, “is to combine the advantages of biologics and ADCs and address their weaknesses. It is a new platform for cancer therapy.”

A team of researchers at the Center for Bioactive Delivery at the University of Massachusetts Amherst’s Institute for Applied Life Sciences has engineered a nanoparticle that has the potential to revolutionize disease treatment, including for cancer. This new research, which appears today in “Angewandte Chemie,”combines two different approaches to more precisely and effectively deliver treatment to the specific cells affected by cancer.

Two of the most promising new treatments involve delivery of cancer-fighting drugs via biologics or antibody-drug conjugates (ADCs). Each has its own advantages and limitations. Biologics, such as protein-based drugs, can directly substitute for a malfunctioning protein in cells. As a result, they have less serious side effects than those associated with traditional chemotherapy. But, because of their large size, they are unable to get into specific cells. ADCs, on the other hand, are able to target specific malignant cells with microdoses of therapeutic drugs, but the antibodies can only carry a limited drug cargo. Since the drugs are more toxic than biologics, increasing the dose of ADCs increases the risk of harmful side effects.

The team’s approach depends on a nanoparticle the team engineered called a “protein-antibody conjugate,” or PAC. “Imagine that the antibodies in PACs are the address on an envelope,” adds Sankaran “Thai” Thayumanavan, distinguished professor in chemistry and interim head of biomedical engineering at UMass, “and that the cancer-fighting protein is the contents of that envelope. The PAC allows us to deliver the envelope with its protected treatment to the correct address. So, safer drugs are delivered to the right cell—the result would be a treatment with fewer side effects.”