Engineering Ionophore Gramicidin-Inspired Self-Assembled Peptides for Drug Delivery and Cancer Nanotherapeutics

Chakraborty, K and Dutta, C and Mukherjee, S and Biswas, A and Gayen, P and George, G and Raghothama, S and Ghosh, S and Dey, S and Bhattacharyya, D and Sinha Roy, R (2018) Engineering Ionophore Gramicidin-Inspired Self-Assembled Peptides for Drug Delivery and Cancer Nanotherapeutics. In: Advanced Therapeutics, 1 (7).

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Abstract

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.

Item Type:	Journal Article
Publication:	Advanced Therapeutics
Publisher:	Blackwell Publishing Ltd
Additional Information:	The copyright for this article belongs to the WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Keywords:	cisplatin; doxorubicin; gramicidin A; ionophore; nanomaterial; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase; octapeptide; peptide; protein p53, antiproliferative activity; apoptosis; Article; cancer therapy; cell viability; controlled study; depolarization; DNA fragmentation assay; drug cytotoxicity; drug delivery system; G2 phase cell cycle checkpoint; human; human cell; MDA-MB-231 cell line; metastatic breast cancer; mitochondrion; MTT assay; nanomedicine; priority journal; protein assembly; protein cleavage; protein engineering; protein expression; S phase cell cycle checkpoint; upregulation; Western blotting
Department/Centre:	Division of Chemical Sciences > NMR Research Centre (Formerly Sophisticated Instruments Facility)
Date Deposited:	02 Aug 2022 12:00
Last Modified:	02 Aug 2022 12:00
URI:	https://eprints.iisc.ac.in/id/eprint/75173

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