Journal article
Functionalized Fluorescent Nanostructures Generated from Self-Assembly of a Cationic Tripeptide Direct Cell-Selective Chemotherapeutic Drug Delivery
ACS applied bio materials, Vol.6(2), pp.836-847
02/20/2023
DOI: 10.1021/acsabm.2c00996
PMID: 36757106
Abstract
Nanodrug delivery systems (NDDs) capable of conveying chemotherapeutics directly into malignant cells without harming healthy ones are of significant interest in the field of cancer therapy. However, the development of nanostructures with the requisite biocompatibility, inherent optical properties, cellular penetration ability, encapsulation capability, and target selectivity has remained elusive. In an effort to develop cell-selective NDDs, we have synthesized a cationic tripeptide Boc-Arg-Trp-Phe-OMe (PA1), which self-assembles into well-ordered spheres in 100% aqueous medium. The inherent fluorescence properties of the peptide PA1 were shifted from the ultraviolet to the visible region by the self-assembly. These fluorescent nanostructures are proteolytically stable, photostable, and biocompatible, with characteristic blue fluorescence signals that permit us to monitor their intracellular entry in real time. We also demonstrate that these tripeptide spherical structures (TPSS) have the capacity to entrap the chemotherapeutic drug doxorubicin (Dox), shuttle the encapsulated drug within cancerous cells, and initiate the DNA damage signaling cascade, which culminates in apoptosis. Next, we functionalized the TPSS with an epithelial-cell-specific epithelial cell adhesion molecule aptamer. Aptamer-conjugated PA1 (PA1-Apt) facilitated efficient Dox delivery into the breast cancer epithelial cell line MCF7, resulting in cell death. However, cells of the human cardiomyocyte cell line AC16 were resistant to the cell killing actions of PA1-Apt. Together, these data demonstrate that not only can the self-assembly of cationic tripeptides like PA1 be exploited for efficient drug encapsulation and delivery but their unique chemistry also allows for functional modifications, which can improve the selectivity of these versatile NDDs.
Details
- Title: Subtitle
- Functionalized Fluorescent Nanostructures Generated from Self-Assembly of a Cationic Tripeptide Direct Cell-Selective Chemotherapeutic Drug Delivery
- Creators
- Subramaniyam Sivagnanam - SRM Institute of Science and TechnologyKiran Das - Centre of Biomedical ResearchIeshita Pan - Saveetha UniversityAtanu Barik - 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.6(2), pp.836-847
- Publisher
- Amer Chemical Soc
- DOI
- 10.1021/acsabm.2c00996
- PMID
- 36757106
- ISSN
- 2576-6422
- eISSN
- 2576-6422
- Number of pages
- 12
- Grant note
- Indian Council of Medical Research; Indian Council of Medical Research (ICMR) Board of Research in Nuclear Sciences (BRNS) , India; Department of Atomic Energy (DAE); Board of Research in Nuclear Sciences (BRNS)
- Language
- English
- Date published
- 02/20/2023
- Academic Unit
- Iowa Neuroscience Institute; Neuroscience and Pharmacology
- Record Identifier
- 9984618507402771
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