Journal article
Supramolecular Structures Generated via Self-Assembly of a Cell Penetrating Tetrapeptide Facilitate Intracellular Delivery of a Pro-apoptotic Chemotherapeutic Drug
ACS applied bio materials, Vol.4(9), pp.6807-6820
09/20/2021
DOI: 10.1021/acsabm.1c00530
PMID: 35006981
Abstract
Development of drug carriers, which can chaperone xenobiotics directly to their site of action, is an essential step for the advancement of precision medicine. Cationic nanoparticles can be used as a drug delivery platform for various agents including chemotherapeutics, oligonucleotides, and antibodies. Self-assembly of short peptides facilitates the formation of well-defined nanostructures suitable for drug delivery, and varying the polarity of the self-assembly medium changes the nature of noncovalent interactions in such a way as to generate numerous unique nanostructures. Here, we have synthesized an ultrashort cell-penetrating tetrapeptide (sequence Lys-Val-Ala-Val), with Lys as a cationic amino acid, and studied the self-assembly property of the BOC-protected (L1) and -deprotected (L2) analogues. Spherical assemblies obtained from L1/L2 in a 1:1 aqueous ethanol system have the ability to encapsulate small molecules and successfully enter into cells, thus representing them as potential candidates for intracellular drug delivery. To verify the efficacy of these peptides in the facilitation of drug efficacy, we generated encapsulated versions of the chemotherapeutic drug doxorubicin (Dox). L1- and L2-encapsulated Dox (Dox-L1 and Dox-L2), similar to the unencapsulated drug, induced upregulation of regulator of G protein signaling 6 (RGS6) and Gβ5, the critical mediators of ATM/p53-dependent apoptosis in Dox-treated cancer cells. Further, Dox-
/
damaged DNA, triggered oxidative stress and mitochondrial dysfunction, compromised cell viability, and induced apoptosis. The ability of Dox-L1 to mediate cell death could be ameliorated via knockdown of either RGS6 or Gβ5, comparable to the results obtained with the unencapsulated drug. These data provide an important proof of principle, identifying L1/L2 as drug delivery matrices.
Details
- Title: Subtitle
- Supramolecular Structures Generated via Self-Assembly of a Cell Penetrating Tetrapeptide Facilitate Intracellular Delivery of a Pro-apoptotic Chemotherapeutic Drug
- Creators
- Subramaniyam Sivagnanam - SRM Institute of Science and TechnologyMadhuri Basak - Centre of Biomedical ResearchAbilesh Kumar - SRM Institute of Science and TechnologyKiran Das - Centre of Biomedical ResearchTarun Mahata - Centre of Biomedical ResearchPriya Rana - SRM Institute of Science and TechnologyAbhishek Singh Sengar - Sanjay Gandhi Post Graduate Institute of Medical SciencesSoumyajit Ghosh - SRM Institute of Science and TechnologyMahesh Subramanian - Bhabha Atomic Research CentreAdele Stewart - Florida Atlantic UniversityBiswanath Maity - Centre of Biomedical ResearchPriyadip Das - SRM Institute of Science and Technology
- Resource Type
- Journal article
- Publication Details
- ACS applied bio materials, Vol.4(9), pp.6807-6820
- DOI
- 10.1021/acsabm.1c00530
- PMID
- 35006981
- ISSN
- 2576-6422
- eISSN
- 2576-6422
- Grant note
- DOI: 10.13039/501100001411, name: Indian Council of Medical Research, award: 5/13/52/2015-NCD-III; DOI: 10.13039/501100001843, name: Science and Engineering Research Board, award: EMR/2016/006873; DOI: 10.13039/501100006593, name: Board of Research in Nuclear Sciences, award: 37(1)/14/09/2017-BRNS/37206
- Language
- English
- Date published
- 09/20/2021
- Academic Unit
- Iowa Neuroscience Institute; Neuroscience and Pharmacology
- Record Identifier
- 9984618522902771
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