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Alginate Supramolecular Hydrogels Based on Viologen and Cucurbit[8]uril: Host-Induced Caveolae-Mediated Endocytosis to White Blood Cancer Cells
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  • Falguni Chandra,
  • Marya Bykova,
  • Vijo Polous,
  • Paltan Laha,
  • Alina Aktanova,
  • Olga Boeva,
  • Margarita Barkovskaya,
  • Ekaterina Pashkina,
  • Na'il Saleh
Falguni Chandra
United Arab Emirates University
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Marya Bykova
Novosibirskij gosudarstvennyj medicinskij universitet Ministerstva zdravoohranenia Rossijskoj Federacii
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Vijo Polous
United Arab Emirates University
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Paltan Laha
United Arab Emirates University
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Alina Aktanova
Novosibirskij gosudarstvennyj medicinskij universitet Ministerstva zdravoohranenia Rossijskoj Federacii
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Olga Boeva
Novosibirskij gosudarstvennyj medicinskij universitet Ministerstva zdravoohranenia Rossijskoj Federacii
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Margarita Barkovskaya
Novosibirskij gosudarstvennyj medicinskij universitet Ministerstva zdravoohranenia Rossijskoj Federacii
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Ekaterina Pashkina
Novosibirskij gosudarstvennyj medicinskij universitet Ministerstva zdravoohranenia Rossijskoj Federacii
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Na'il Saleh
UAE University

Corresponding Author:n.saleh@uaeu.ac.ae

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Abstract

The cellular uptake of drug carriers to the cytosol of a specific cell remains challenging, and a non-classical supramolecular strategy is motivated. Here, we select a model host-guest complex in which a diamino-viologen (VG) fluorescent tag was engulfed by cucurbit[8]uril (CB8) and covalently linked to alginate polysaccharides (ALG) as the modified drug vehicle. When adsorbed on the ALG surface, the encapsulation of VG was first confirmed utilizing FTIR and NMR spectroscopic methods. Solid optical measurements (DRS, PL, and TRPL) revealed emissive materials at around 650 nm and that CB8 enhanced the rigidity of the modified hydrogel. The molar composition of 2 to 1 for the complexation of VG to CB8 on the alginate surface and the thermal stabilities were also confirmed using TGA and DSC techniques. CB8 induced a dramatic decrease in the average size of the VGALG polysaccharides from 485 to 165 nm and a turnover in their charge from -19.8 to +14.4 mV. Flow cytometry with inhibitors of various endocytosis pathways was employed to track the cellular uptake across different blood cell types: human T-cell leukemia 1301 and peripheral blood mononuclear cells. Noticeably, complexation of VG to CB8 host on top of the sugar platform dramatically enhanced the internalization to 1301 cells (viz. from 1 to 99%) at a concentration of 1.8 mg/mL via caveolae-mediated endocytosis (CvME) because of the size reduction, turnover in the charge from negative to positive, and rigidity induction. These observations reveal a more profound understanding of the macrocyclic effects on drug delivery
06 Jul 2023Submitted to View
17 Jul 2023Submission Checks Completed
17 Jul 2023Assigned to Editor
17 Jul 2023Review(s) Completed, Editorial Evaluation Pending
17 Jul 2023Reviewer(s) Assigned
24 Aug 2023Editorial Decision: Revise Major
29 Aug 20231st Revision Received
01 Sep 2023Submission Checks Completed
01 Sep 2023Assigned to Editor
01 Sep 2023Review(s) Completed, Editorial Evaluation Pending
01 Sep 2023Reviewer(s) Assigned
15 Sep 2023Editorial Decision: Revise Minor
17 Sep 20232nd Revision Received
20 Sep 2023Submission Checks Completed
20 Sep 2023Assigned to Editor
20 Sep 2023Review(s) Completed, Editorial Evaluation Pending
21 Sep 2023Editorial Decision: Accept