Cystine-cored diphenylalanine appended peptide-based self-assembled fluorescent nanostructures direct redox-responsive drug delivery

Suman Nayak; Kiran Das; Subramaniyam Sivagnanam; Shyamvarnan Baskar; Adele Stewart; Dinesh Kumar; Biswanath Maity; Priyadip Das

doi:10.1016/j.isci.2024.109523

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Cystine-cored diphenylalanine appended peptide-based self-assembled fluorescent nanostructures direct redox-responsive drug delivery

Journal article

Open access

Peer reviewed

Cystine-cored diphenylalanine appended peptide-based self-assembled fluorescent nanostructures direct redox-responsive drug delivery

Suman Nayak, Kiran Das, Subramaniyam Sivagnanam, Shyamvarnan Baskar, Adele Stewart, Dinesh Kumar, Biswanath Maity and Priyadip Das

iScience, Vol.27(4), pp.109523-109523

04/19/2024

DOI: 10.1016/j.isci.2024.109523

PMCID: PMC10993133

PMID: 38577103

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Abstract

Fabrication of stimuli-responsive superstructure capable of delivering chemotherapeutics directly to the cancer cell by sparing healthy cells is crucial. Herein, we developed redox-responsive hollow spherical assemblies through self-assembly of disulfide-linked cysteine-diphenylalanine (SN). These fluorescent hollow spheres display intrinsic green fluorescence, are proteolytically stable and biocompatible, and allow for real-time monitoring of their intracellular entry. The disulfide bond facilitates selective degradation in the presence of high glutathione (GSH) concentrations, prevalent in cancer cells. We achieved efficient encapsulation (68.72%) of the anticancer drug doxorubicin (Dox) and demonstrated GSH-dependent, redox-responsive drug release within cancerous cells. SN-Dox exhibited a 20-fold lower effective concentration (2.5 μM) for compromising breast cancer cell viability compared to non-malignant cells (50 μM). The ability of SN-Dox to initiate DNA damage signaling and trigger apoptosis was comparable to that of the unencapsulated drug. Our findings highlight the potential of SN for creating site-specific drug delivery vehicles for sustained therapeutic release. [Display omitted] •Redox-responsive hollow spheres enable intracellular site-specific drug delivery•Elevated glutathione levels in cancer cells trigger the drug release.•Fluorescent SN-Dox offers real-time intracellular monitoring of drug release.•SN-Dox exhibits lower effective concentration for breast cancer cell viability. Drug delivery system; Molecular self-assembly; Peptides; Biomaterials; Nanostructure

Biomaterials

Drug delivery system

Molecular self-assembly

Nanostructure

Peptides

Details

Title: Subtitle: Cystine-cored diphenylalanine appended peptide-based self-assembled fluorescent nanostructures direct redox-responsive drug delivery
Creators: Suman Nayak - SRM Institute of Science and Technology
Kiran Das - Centre of Biomedical Research
Subramaniyam Sivagnanam - SRM Institute of Science and Technology
Shyamvarnan Baskar - SRM Institute of Science and Technology
Adele Stewart - Florida Atlantic University
Dinesh Kumar - Centre of Biomedical Research
Biswanath Maity - Centre of Biomedical Research
Priyadip Das - SRM Institute of Science and Technology
Resource Type: Journal article
Publication Details: iScience, Vol.27(4), pp.109523-109523
DOI: 10.1016/j.isci.2024.109523
PMID: 38577103
PMCID: PMC10993133
NLM abbreviation: iScience
ISSN: 2589-0042
eISSN: 2589-0042
Publisher: Elsevier Inc
Grant note: DOI: 10.13039/501100006593, name: Board of Research in Nuclear Sciences; DOI: 10.13039/501100001411, name: Indian Council of Medical Research
Language: English
Date published: 04/19/2024
Academic Unit: Iowa Neuroscience Institute; Neuroscience and Pharmacology
Record Identifier: 9984618635202771

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