Future pandemics（流行的，普遍的） of seasonal¹ flu, H1N1 and other drug-resistant² viruses may be thwarted³（反对，挫败） by a potent⁴（有效的，强有力的） , immune-boosting payload that is effectively delivered to cells by gold nanorods, report scientists at the University at Buffalo⁵ and the U.S. Centers for Disease Control and Prevention. The work is published in the current issue of the Proceedings⁶ of the National Academy of Sciences. "This joint⁷ research by UB and the CDC has the potential to usher⁸ in（引进） a new generation of antiviral（抗病毒的） medicines to aggressively treat a broad range of infectious diseases, from H1N1 to avian flu（禽流感） and perhaps Ebola（埃博拉病毒） , that are becoming increasingly resistant to the medicines used against them," says UB team leader Paras Prasad, PhD, executive director of the UB Institute for Lasers, Photonics and Biophotonics (ILPB) and SUNY Distinguished⁹ Professor in the departments of Chemistry, Physics, Electrical Engineering and Medicine.

The collaborative work between UB and CDC came together through the work of Krishnan Chakravarthy, an MD/PhD candidate at UB and the paper's first author. This research constitutes part of his doctoral degree work that focused on host response to influenza¹⁰ infection and novel drug delivery strategies.

The paper describes the single strand¹¹ RNA molecule¹², which prompts a strong immune response against the influenza virus by ramping¹³ up the host's cellular¹⁴ production of interferons（干扰素） , proteins that inhibit¹⁵ viral replication.

But, like most RNA molecules¹⁶, they are unstable¹⁷ when delivered into cells. The gold nanorods produced at UB act as an efficient vehicle to deliver into cells the powerful immune activator¹⁸ molecule.

"It all boils down to how we can deliver the immune activator," says Suryaprakesh Sambhara, DVM, PhD, in CDC's Influenza Division and a co-author on the paper. "The UB researchers had an excellent delivery system. Dr. Prasad and his team are well-known for their contributions to nanoparticle delivery systems."

A key advantage is gold's biocompatibility（生物相容性） .

"The gold nanorods protect the RNA from degrading once inside cells, while allowing for more selected targeting of cells," said co-author Paul R. Knight¹⁹ III, MD, Chakravarthy's thesis advisor²⁰; professor of anesthesiology（麻醉学） , microbiology and infectious diseases in the UB School of Medicine and Biomedical Sciences; and director of its MD/PhD program.

"This work demonstrates that the modulation²¹ of host response is going to be critical to the next generation of anti-viral therapies," Chakravarthy explains. "The novelty of this approach is that most of these kinds of RNA viruses share a common host-response immune pathway; that is what we have targeted with our nanoparticle therapy. By enhancing the host immune response, we avoid the difficulty of ongoing²² viral resistance generated through mutations."

Diseases that could be effectively targeted with this new approach include any viruses that are susceptible²³ to the innate²⁴（先天的，固有的） immune response that type 1 interferons（干扰素） trigger, Prasad notes.

Based on these in vitro results, the UB and CDC researchers are beginning animal studies.

"This collaboration²⁵ has been extraordinary as two disparate（全异的，不同的） research groups at UB and a third at the CDC have managed to maintain progress toward a common goal: treatment of influenza," says co-author Adela Bonoiu, PhD, UB research assistant professor at ILPB.

Important funding for the UB institute portion of the research was provided by the John R. Oishei Foundation, which helped pave the way for new stimulus²⁶ funding UB received recently from the National Institutes of Health to further develop this strategy. The goal is to work toward an Investigational²⁷ New Drug filing with the FDA.