Tissue Engineering And Nanotheranostics

(Steven Felgate) #1
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

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