Dr. Nibedita Sanyal Profile

Dr. Nibedita Sanyal

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Proceedings Article | 20 February 2018 Paper

Effect of linkers on the αvβ3 integrin targeting efficiency of cyclic RGD-conjugates.

Partha Karmakar, Dorota Grabowska, Gail Sudlow, Kostiantyn Ziabrev, Nibedita Sanyal, Samuel Achilefu

Proceedings Volume 10508, 1050809 (2018) https://doi.org/10.1117/12.2301223

KEYWORDS: Tumors, In vivo imaging, Luminescence, Confocal microscopy, Cancer, Breast cancer, Chemistry, Near infrared, Imaging systems, Near infrared spectroscopy

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Cyclic arginine-glycine-aspartic acid (cRGD) peptides are well known to target α_νβ₃ integrin expressed on cancer cells and neovasculature. Conjugation of these peptides with dyes, drugs, antibodies and other biomolecules through covalent linkers provides a facile way to deliver these products to tumor cells for targeted cancer therapy and diagnosis. Click chemistry and acid-amine couplings are widely used conjugation strategies. However, the effects of different linkers and the distance between the cRGD and the conjugates on the binding of cRGD ligand with α_νβ₃ has been underexplored.

In this present study, we prepared cRGD-conjugates using different linkers and determined how they altered the tumor targeting efficiency in vitro and in vivo. The results demonstrate that different linkers significantly altered the pharmacokinetics of the cRGD conjugates and the tumor uptake kinetics. Unlike large antibodies, this preliminary finding shows that linkers used to attach drugs and fluorescent molecular probes to small peptides play a major role in the accuracy of tumor targeting and treatment outcomes. As a result, considerable attention should be paid to the nature of linkers used in the design of molecular probes and targeted therapeutics.

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