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
"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."
ACS Nano 2014.