b2815 Tissue Engineering and Nanotheranostics “9.61x6.69”
240 Tissue Engineering and Nanotheranostics
DOX (Doxil, Caelyx) is a formulation of DOX in PEGcoated
liposomes with a prolonged circulation time and unique toxicity pro
file used against numerous forms of cancer. Due to its wide range of
indications, it is one of the most widely used anticancer drugs in the
market. It must be said that Doxil also has adverse side effects associ
ated with its administration, which include common symptoms, such
as hair loss, vomiting, handfoot syndrome, and cardiomyopathy.212,213
The studies show that the mechanism of action of doxorubicin is
mainly through interaction with DNA via intercalation.^214 Paclitaxel
was discovered and isolated from the bark of the Pacific yew, Taxus
brevifolia. The mechanism of action of PTX to the cancer cells is
mainly through promoting tubulin polymerization and preventing its
depolymerization which could block the tumor cells in mitosis phase.
Clinical treatment results display that PTX have good therapeutic
effect against a series of solid tumors including breast cancer, ovarian
cancer, nonsmall cell lung cancer and head and neck cancer. The
water solubility of PTX is very poor, therefore the traditional injection
of PTXtaxol uses polyoxyethylene castor oil and ethanol as solubiliz
ing agent to improve the solubility of PTX in water for injection.
However, polyoxyethylene castor oil can cause some undesirable side
effects such as allergic reaction etc. In 2005, Abraxane (albumin
bound PTX) was from the company of Abraxis BioScience approved
by Food and Drug Administration (FDA). Abraxane has abandoned
traditional solubilizing agent of polyoxyethylene castor oil and taken
human serum albumin (HSA) as the carrier and stabilizer. Thanks to
good biocompatibility and low toxicity of HAS originating from the
human body, the maximum tolerated dose of Abraxane is much
higher than that of taxol. In addition, HAS can pass through the vas
cular endothelial cells through GP60 receptor and into the tumor
tissue. Subsequently, HAS could specifically bind to the protein of
SPARC, distributed on the surface of tumor cells and deliver PTX
into the tumor cells. The clinical curative effect of Abraxane is better
than taxol. Nucleic acidbased therapies by siRNA and miRNAs have
gained applications in the treatment of various forms of cancers.
Because miRNAs play a role in increasing chemoresistance of both
breast cancer cells and prostate cancer cells, they can be applied for