Biomedical Engineering Reference
In-Depth Information
been found to overcome loss in biological activity and decrease in immunogenic-
ity (Goodson and Katre 1990). The purpose of tagging enzymes with PEG for can-
cer therapy arises from the fact that cancer cells are auxotrophic for certain amino
acids like methionine arginine and asparagine which they cannot synthesis them-
selves. In such cases use of PEG tagged Methioninase (Hoffman and Jacobsen
1980; Guo et al. 1993; Kokkinakis et al. 1997), arginine deiminase and asparagi-
nase (Elspar and Erwinia L-asparaginase) have been found to deprive the cancer
cells of these essential amino acids which hampers their uncontrolled proliferation
and thus tumorogenesis. Such PEGylated proteins for cancer treatment can syn-
ergise the anticancer potential of many drugs by simultaneously acting as carriers
for them (Gianfranco et al. 2008). Apart from this, many poly(amino acid)-PEG
micelle systems are being tested in phase I clinical trials.
PEG Based Micelle System for Cancer Theranostics
PEG conjugated polymeric micelles have had their fair share of success in deliv-
ering hydrophobic anticancer drugs. The PLA-PEG is one such conjugate system
which has been already commercialized by the name Genexol-PM and is used for
breast cancer treatments. Inclusion of suitable imaging agent in such established
PEG based delivery systems can streamline the clinical evaluation of such formu-
lation (Kim et al. 2004). One prominent reason for extensive use of PEG is that it
is FDA approved biodegradable polymer which tends to prolong circulation time
significantly and thereby improves the therapeutic outcome (Owens and Peppas
2006). A specific set of enzyme susceptible polymers are also utilized in conju-
gation with PEG which enables further functionalization and site specific release
of bioactive molecules (Avgoustakis 2004). A docetaxel loaded PEG-PCL micel-
lar system encapsulated within pH-responsive hydrogel was formulated by Wang
et al. for treating breast cancer (4T1 cells). The pH responsiveness and reversibil-
ity of the hydrogel decreased the systemic toxicity and simultaneously increased
the drug bioavailability in the vicinity of cancer cells. The therapeutic outcomes
were validated by cell viability and immunofluorescence studies. One such pol-
yester based polymer is PLL which was used by Liu et al. to synthesize PLL-
PEG-PLL triblock copolymer and was later coupled with MRI contrast agent,
gadolinium diethylene triamine penta acetic acid (Gd-DTPA). Additionally a can-
cer cell specific antibody against vascular endothelial growth factor (VEGF) was
grafted onto the surface of this system improve its in vitro (
H22
) and in vivo thera-
peutic efficacy (Liu et al. 2011). As a follow up of this work another group syn-
thesized a diblock copolymer PEG-PLA and poly(2-hydroxylethylmethacrylatehi
stidine)-g-poly-(d,l-lactide) (PHEMA-g-PLA) and loaded them with hydrophobic
drug doxorubicin in the core which were further functionalized on the surface with
folic acid moieties to attain cancer targeted therapy. An additional imaging compo-
nent Cy5.5 was also attached to the terminal ends of PEG-PLA for simultaneous
diagnosis of cancer. The system showed improved cancer detection under in vivo
conditions with clear fluorescence contrast at the tumor site (Tsai et al. 2010).
