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Biol Med Case Rep 2017 | Volume 1 Issue 2
November 06-07, 2017 | New Orleans, USA
Nanomedicine & Healthcare
Global Meet on
Statement of the problem:
Themost common chemotherapy
regimen for treating cancer is based on the application of
nonspecific cytotoxic substances which can induce toxic side
effects. Targeted cancer therapy is a powerful therapeutic
strategy to management of cancer. HER2 as an anticancer
target has long been studied. Its overexpression plays an
important role in the pathogenesis and progressiveness of
breast and other cancers.
Methodology & theoretical orientation:
To establish efficient
and reliable drug delivery to HER2-overexpressing cells, the
authors of this study have developed anti-HER2 (ErbB2)
peptide-liposomal formulations of doxorubicin (DOX) by
an engineered breast tumor targeting peptide ligand,
AHNP, anti-HER2/neu peptide, (FCDGFYACYADV) with three
glycine amino acids as spacer before its original sequencing.
Towards this goal, PEGylated liposome doxorubicin (PLD)
bearing different ligand densities of AHNP was prepared
and characterized for their size, zeta potential and peptide
conjugation. The AHNP functionalization and density
effects on breast tumor cell uptake, selective cytotoxicity,
prevention of tumor growth and the tissue biodistribution of
encapsulated DOX were studied in mice bearing TUBO breast
cancer tumor model.
Findings:
The findings demonstrated that increasing the
ligand density of AHNP increases cytotoxicity and cell-uptake
in SKBR3 and TUBO cells which overexpress HER2 but not
in MDA-MB-231 with low HER2 expression profile. The
anticancer activity was also superior for targeted liposomal
DOX with more AHNP densities.
Conclusion & significance:
This experiment displayed the great
potential of AHNP as a targetingmoiety on the liposome surface
and emphasized the significance of adjusting density of ligand
tomaximize the targeting capability of the nano drug delivery
systems. Overall, the results showed that optimum AHNP
density functionalization of PLD can significantly improve
selectivity and the therapeutic index of liposomal DOX in the
treatment of HER2 positive breast cancer and merits further
investigation.
e:
zahmatkeshan@razi.tums.ac.irImproved drug delivery and therapeutic efficacy of PEGylated liposomal doxorubicin by targeting anti-HER2
peptide inmurine breast tumormodel
Masoumeh Zahmatkeshan
TUMS, Iran