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
Affiliations
Suman Nayak
Department of Chemistry, SRM Institute of Science and Technology, SRM Nagar, Potheri, Kattankulathur, Tamil Nadu 603203, India
Kiran Das
Department of Systems Biology, Centre of Biomedical Research (CBMR), SGPGI campus, Raebareli Road, Lucknow, Uttar Pradesh 226014, India
Subramaniyam Sivagnanam
Department of Chemistry, SRM Institute of Science and Technology, SRM Nagar, Potheri, Kattankulathur, Tamil Nadu 603203, India
Shyamvarnan Baskar
Department of Chemistry, SRM Institute of Science and Technology, SRM Nagar, Potheri, Kattankulathur, Tamil Nadu 603203, India
Adele Stewart
Department of Biomedical Science, Charles E. Schmidt College of Medicine, Florida Atlantic University, Jupiter, FL 33458, USA
Dinesh Kumar
Department of Advanced Spectroscopy and Imaging, Centre of Biomedical Research (CBMR), SGPGI campus, Raebareli Road, Lucknow, Uttar Pradesh 226014, India
Biswanath Maity
Department of Systems Biology, Centre of Biomedical Research (CBMR), SGPGI campus, Raebareli Road, Lucknow, Uttar Pradesh 226014, India; Corresponding author
Priyadip Das
Department of Chemistry, SRM Institute of Science and Technology, SRM Nagar, Potheri, Kattankulathur, Tamil Nadu 603203, India; Corresponding author
Summary: 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.
