Abstract
Receptor-mediated drug delivery systems are a promising tool for targeting malignant cells to suppress/inhibit the malignancy without disturbing healthy cells. Protein-based nanocarrier systems possess numerous advantages for the delivery of variety of chemotherapeutics, including therapeutic peptides and genes. In the present work, glucose-conjugated camptothecin-loaded glutenin nanoparticles (Glu-CPT-glutenin NPs) were fabricated to deliver camptothecin to MCF-7 cells via GLUT-1 transporter protein. Initially, Glu-conjugated glutenin polymer was successfully synthesized through reductive amination reaction, and this was confirmed by FTIR and 13C-NMR. Then, camptothecin (CPT) was loaded into Glu-conjugated glutenin polymer forming Glu-CPT-glutenin NPs. The nanoparticles were studied for their drug releasing capacity, morphological shape, size, physical nature, and zeta potential. The fabricated Glu-CPT-glutenin NPs were found to be spherical in shape and amorphous in nature with 200-nm size range and a zeta potential of − 30 mV. Furthermore, MTT assay using Glu-CPT-glutenin NPs confirmed concentration-dependent cytotoxicity against MCF-7 cells after 24-h treatment, and IC50 was found to be 18.23 μg mL−1. In vitro cellular uptake study demonstrated that the Glu-CPT-glutenin NPs had enhanced endocytosis and delivered CPT in MCF-7 cells. A typical apoptotic morphological change of condensed nuclei and distorted membrane bodies was found after treatment with IC50 concentration of NPs. The released CPT from NPs also targeted mitochondria of MCF-7 cells, significantly increasing the level of reactive oxygen species and causing the damage of mitochondrial membrane integrity. These outcomes confirmed that the wheat glutenin can positively serve as a significant delivery vehicle and enhance the anticancer potential of this drug.
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Acknowledgements
Raja Rajeshwari thanks KARE for the university research fellowship. The authors are grateful to the management of Kalasalingam Academy of Research and Education, Krishnankoil, India, for providing research facilities.
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SK and RRR gratefully acknowledge the Management of Kalasalingam Academy of Research and Education for Seed Money Grant (KARE/VC/R&D/SMPG/2021–2022/1) and Research Fellowship, respectively.
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R.R.R, P.P, T.P, D.V, S.R.K, K.S.J, S.V, A.J, A.S.K, K.S. and S.K. conceived and designed the research. R.R.R, S.R.K, P.P, D.V, K.S.J, A.J. and S.K. conducted the experiments. S.R.K, D.V, T.P, P.P. and S.K. analyzed the data. K.S, S.R.K, DV, and S.K. wrote the manuscript. All authors read and approved the manuscript. All data were generated in house and no paper mill was used.
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Rajeshkumar, R.R., Pavadai, P., Panneerselvam, T. et al. Glucose-conjugated glutenin nanoparticles for selective targeting and delivery of camptothecin into breast cancer cells. Naunyn-Schmiedeberg's Arch Pharmacol 396, 2571–2586 (2023). https://doi.org/10.1007/s00210-023-02480-y
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DOI: https://doi.org/10.1007/s00210-023-02480-y