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Reuters Health Information: Triptolide nanoformulation targets liver cancer cells

Triptolide nanoformulation targets liver cancer cells

Last Updated: 2014-09-03

By Will Boggs MD

NEW YORK (Reuters Health) - A pH-sensitive, folate-coated triptolide nanoformulation safely targets hepatocellular carcinoma (HCC) cells, researchers from Korea and Singapore report.

"The toxicity of drugs can be drastically reduced by tumor-specific targeting," Dr. Kam Man Hui from National Cancer Center Singapore, Yong Loo Lin School of Medicine, Singapore told Reuters Health by email. "This opens the possibility to re-examine many of the drug candidates that are not being clinically developed because of their high toxicity."

Triptolide is one such drug. Though it has been shown to be effective against many malignant cancer types, its poor solubility and extremely high toxicity have limited its potential clinical application.

Dr. Hui and colleagues took advantage of the more acidic cellular milieu of cancer cells and the overexpression of folate receptor by a subpopulation of HCC cells by creating a pH-sensitive triptolide nanoformulation coated with folate.

Not only did the formulation demonstrate strong inhibition of HCC growth, it also had decreased cytotoxicity against normal liver cells, according to the August 5th ACS Nano online report.

Following treatment with this nanoformulation, HCC cells showed both CKS2 and AURKA to be significantly downregulated. In separate studies, high-level expression of CKS2 and AURKA was significantly associated with patient survival.

In a mouse model of HCC, survival after three months was about 80% among mice treated with the nanoformulation, compared with about 50% among mice treated with free triptolide and only about 30% among untreated controls.

Immunohistochemistry showed significantly lower expression of CKS2 and AURKA in the nanoformulation-treated tumor tissues from these mice compared with tissues from free triptolide-treated or untreated tumor tissues.

"Our technology is quite versatile," Dr. Hui said. "It can easily be applied to other human tumors, such as ovarian tumor that expresses high level of the targeting molecules (the folate receptor). In addition, our technology can be applied to other types of tumor by modifying/customizing the targeting molecules specific for the tumor type."

"To put our research into clinical trials, the major generic challenges include: to manufacture sufficient quantity of the nanoparticles under a certified GMP facility; (and) to determine the pharmacokinetics and pharmacodynamics of the drug-conjugated nanoparticles in vivo," Dr. Hui said. "These problems are being systematically solved in our laboratories in Korea and at the National Cancer Center Singapore."

Co-authors Dr. Daishun Ling and Dr. Taeghwan Hyeon from Seoul National University, Seoul, Korea added in a joint email, "Material scientists have to collaborate more closely with clinicians and biologists to solve real problems in medicine such as cancer treatment."

SOURCE: http://bit.ly/1pJIDm4

ACS Nano 2014.

 
 
 
 
                               
 
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