By Katharine Jackson and Luc Cohen

(Reuters) - The United States has charged leaders of the Mexico-based Sinaloa Cartel with running a fentanyl trafficking operation fueled by Chinese chemical and pharmaceutical companies, U.S. Attorney General Merrick Garland said on Friday.

Three sons of Joaquin "El Chapo" Guzman, the onetime leader of the Sinaloa Cartel now imprisoned in the United States, were among those charged in what authorities called one of the most ambitious responses to date to a drug epidemic that has killed hundreds of thousands of Americans in the past eight years.

"We're going after the entire network, from precursors, to importation into Mexico, to the manufacturer, to the weapons, to the money launderers, to the distribution in the United States," Garland told reporters.

Federal prosecutors unsealed three separate indictments charging more than two dozen defendants based in Mexico, China and Guatemala, eight of whom are in custody. Among those awaiting extradition is Ovidio Guzman Lopez, one of El Chapo's sons, who was arrested in Mexico earlier this year.

He was indicted in Manhattan federal court on six counts, including conspiracy to import and distribute fentanyl, and faces a mandatory life sentence if convicted.

"They know that they're poisoning and killing Americans. They just don't care because they make billions of dollars doing it," Anne Milgram, chief of the U.S. Drug Enforcement Administration, said of Guzman's sons. "Their greed is shocking and without bounds."

Prosecutors also charged four owners of Chinese companies that allegedly provided precursor chemicals to the cartel.

The U.S. Treasury Department on Friday also slapped sanctions on China-based chemical companies Wuhan Shuokang Biological Technology Co Ltd and Suzhou Xiaoli Pharmatech Co Ltd.

Garland said U.S. officials had met with Mexican counterparts this week and would work with them to "continually strike against this enemy" and seek extradition of the remaining defendants. He also called on China to do more.

"The PRC government must stop the unchecked flow of fentanyl precursor chemicals that are coming out of China," he said, referring to the People's Republic of China.

(Reporting by Katharine Jackson in Washington and Luc Cohen in New York; editing by Jonathan Oatis and Bill Berkrot)