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Engineering Ionophore Gramicidin‐Inspired Self‐Assembled Peptides for Drug Delivery and Cancer Nanotherapeutics
Author(s) -
Chakraborty Kasturee,
Dutta Chiranjit,
Mukherjee Sanchita,
Biswas Abhijit,
Gayen Paramita,
George Gijo,
Raghothama Srinivasarao,
Ghosh Snehasish,
Dey Souvik,
Bhattacharyya Dhananjay,
Sinha Roy Rituparna
Publication year - 2018
Publication title -
advanced therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.125
0ISSN - 2366-3987
DOI - 10.1002/adtp.201800018
Subject(s) - doxorubicin , nanomedicine , apoptosis , cytotoxicity , peptide , chemistry , cancer cell , drug delivery , cytotoxic t cell , cancer research , biochemistry , cancer , biology , materials science , nanotechnology , chemotherapy , in vitro , nanoparticle , genetics
Nature‐inspired self‐assembled peptide‐based nanoscale materials are of great interest for biomedical applications. Here, ionophore gramicidin‐inspired designed nanoscale materials for drug delivery and cancer nanotherapeutics are reported. The length dependent formation of diverse nanoarchitectures by experimental and computational studies from gramicidin‐inspired sequences is explored and their therapeutic potential is evaluated. Mechanistic studies revealed that gramicidin A (gA) and gramicidin‐inspired octapeptide (LD8) induce cytotoxic effects, mitochondrial depolarization, and apoptotic cell death against metastatic breast cancer cell line MDA‐MB‐231. Doxorubicin loaded LD8 peptide (LD8‐Dox‐NP) and doxorubicin loaded gramicidin (gA‐Dox‐NP) show cytotoxicity determined by MTT assay and apoptosis as evidenced by DNA fragmentation study and Western blot analysis of poly (ADP‐ribose) polymerase (PARP) expression and cleavage. gA‐Dox‐NP and LD8‐Dox‐NP treated MDA‐MB‐231 cells show upregulation of tumor suppressor protein p53, which can inhibit cell proliferation. Interestingly, cell cycle analysis suggests that gA‐Dox‐NP and LD8‐Dox‐NP induce S and G2 phase cell cycle arrest, respectively. These data establish gA and LD8 peptide as new potential anticancer therapeutics against metastatic breast cancer and suggest that gA‐Dox‐NP and LD8‐Dox‐NP can be potentially used as two‐in‐one nanomedicine for treating breast cancer.