Alginate supramolecular hydrogels based on viologen and cucurbit[8]uril: Host-induced caveolae-mediated endocytosis to white blood cancer cells

Falguni Chandra, Maria Bykova, Vijo Poulose, Paltan Laha, Alina Aktanova, Olga Boeva, Margarita Barkovskaya, Ekaterina Pashkina, Na'il Saleh

Research output: Contribution to journalArticlepeer-review

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 (1,1′-bis(4-aminophenyl)-[4,4′-bipyridine]−1,1′-diium dichloride [VG]) fluorescent tag was engulfed by cucurbit[8]uril (CB8) and covalently linked to alginate polysaccharides (alginic acid [ALG]) as the modified drug vehicle. When adsorbed on the ALG surface, the encapsulation of VG was first confirmed utilizing Fourier transform infrared and nuclear magnetic resonance spectroscopic methods. Solid optical measurements (diffuse reflectance spectroscopy, photoluminescence, and time-resolved photoluminescence) revealed emissive materials at around 650 nm and that CB8 enhanced the rigidity of the modified hydrogel. The molar composition of 2:1 for the complexation of VG to CB8 on the alginate surface and the thermal stabilities were also confirmed using thermogravimetric analysis and differential scanning calorimetry 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 with the CB8 host on top of the sugar platform dramatically enhanced the internalization into 1301 cells (viz. from 1% to 99%) at a concentration of 1.8 mg/mL via caveolae-mediated endocytosis 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.

Original languageEnglish
Article number20230058
JournalVIEW
Volume4
Issue number6
DOIs
Publication statusPublished - Dec 2023

Keywords

  • alginates
  • blood cancer cells
  • cellular uptake
  • cucurbiturils
  • time-resolved photoluminescence
  • viologen

ASJC Scopus subject areas

  • Biomaterials
  • Biomedical Engineering

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