TY - JOUR
T1 - Downregulation of NT5C3 gene expressions by elastin-like polypeptide gemcitabine conjugate for ovarian cancer therapy
AU - Ramamurthi, Deepthi
AU - Selvaraj, Jubie
AU - Raj, P. Vasanth
AU - Tallapaneni, Vyshnavi
AU - Chandrasekar, Moola Joghee Nanjan
PY - 2022/10
Y1 - 2022/10
N2 - Due to the undesirable side effects and lack of target specificity of existing anticancer drugs the newer drug delivery system with target specificity and undesirable side effects are, therefore, essential today. Given that sensitive polymers, peptides, dendrimers and hydrogels have been widely investigated as carriers for controlled release and target specificity, it is still a challenge to overcome the cumbersome problems faced in cancer treatment. Elastin like – polypeptide is genetically designed as VPGXG, ‘n’ times where ‘X’ can be any amino acid except proline. In the present study, the peptide VPGVG and VPGVG gemcitabine conjugate were synthesized using solid phase peptide synthesis method and the successful synthesis and conjugation of gemcitabine were confirmed by Fourier Transform Infrared spectroscopy (FTIR), Nuclear Magnetic Resonance (NMR) and Liquid Chromatography Mass Spectrometry (LCMS) studies. The isoelectric point calculator, differential scanning calorimetry, in vitro drug release studies revealed the thermosensitive and pH sensitive nature of the peptide. The in vitro 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and gene expression studies have been performed to evaluate the tumor targeting potential of VPGVG gemcitabine conjugate. We conclude that the peptide VPGVG can be used with certain advantages over naturally occurring long Elastin Like Polypeptides for targeting anticancer drugs to intra-cellular space.
AB - Due to the undesirable side effects and lack of target specificity of existing anticancer drugs the newer drug delivery system with target specificity and undesirable side effects are, therefore, essential today. Given that sensitive polymers, peptides, dendrimers and hydrogels have been widely investigated as carriers for controlled release and target specificity, it is still a challenge to overcome the cumbersome problems faced in cancer treatment. Elastin like – polypeptide is genetically designed as VPGXG, ‘n’ times where ‘X’ can be any amino acid except proline. In the present study, the peptide VPGVG and VPGVG gemcitabine conjugate were synthesized using solid phase peptide synthesis method and the successful synthesis and conjugation of gemcitabine were confirmed by Fourier Transform Infrared spectroscopy (FTIR), Nuclear Magnetic Resonance (NMR) and Liquid Chromatography Mass Spectrometry (LCMS) studies. The isoelectric point calculator, differential scanning calorimetry, in vitro drug release studies revealed the thermosensitive and pH sensitive nature of the peptide. The in vitro 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and gene expression studies have been performed to evaluate the tumor targeting potential of VPGVG gemcitabine conjugate. We conclude that the peptide VPGVG can be used with certain advantages over naturally occurring long Elastin Like Polypeptides for targeting anticancer drugs to intra-cellular space.
U2 - 10.1016/j.jddst.2022.103821
DO - 10.1016/j.jddst.2022.103821
M3 - Article
SN - 1773-2247
VL - 76
JO - Journal of Drug Delivery Science and Technology
JF - Journal of Drug Delivery Science and Technology
M1 - 103821
ER -
