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

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

iScience. 2024 Mar 16;27(4):109523. doi: 10.1016/j.isci.2024.109523. eCollection 2024 Apr 19.

Authors

Suman Nayak¹, Kiran Das², Subramaniyam Sivagnanam¹, Shyamvarnan Baskar¹, Adele Stewart³, Dinesh Kumar⁴, Biswanath Maity², Priyadip Das¹

Affiliations

¹ Department of Chemistry, SRM Institute of Science and Technology, SRM Nagar, Potheri, Kattankulathur, Tamil Nadu 603203, India.
² Department of Systems Biology, Centre of Biomedical Research (CBMR), SGPGI campus, Raebareli Road, Lucknow, Uttar Pradesh 226014, India.
³ Department of Biomedical Science, Charles E. Schmidt College of Medicine, Florida Atlantic University, Jupiter, FL 33458, USA.
⁴ Department of Advanced Spectroscopy and Imaging, Centre of Biomedical Research (CBMR), SGPGI campus, Raebareli Road, Lucknow, Uttar Pradesh 226014, India.

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.

Keywords: Biomaterials; Drug delivery system; Molecular self-assembly; Nanostructure; Peptides.