Polysaccharide conjugates surpass monosaccharide ligands in hepatospecific targeting – Synthesis and comparative in silico and in vitro assessment

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Polysaccharide conjugates surpass monosaccharide ligands in hepatospecific targeting – Synthesis and comparative in silico and in vitro assessment. / Dhawan, V.; Joshi, G.; Sutariya, B.; Shah, J.; Ashtikar, M.; Nagarsekar, K.; Steiniger, F.; Lokras, A.; Fahr, A.; Krishnapriya, M.; Warawdekar, U.; Saraf, M.; Nagarsenker, M.

In: Carbohydrate Research, Vol. 509, 108417, 2021.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Dhawan, V, Joshi, G, Sutariya, B, Shah, J, Ashtikar, M, Nagarsekar, K, Steiniger, F, Lokras, A, Fahr, A, Krishnapriya, M, Warawdekar, U, Saraf, M & Nagarsenker, M 2021, 'Polysaccharide conjugates surpass monosaccharide ligands in hepatospecific targeting – Synthesis and comparative in silico and in vitro assessment', Carbohydrate Research, vol. 509, 108417. https://doi.org/10.1016/j.carres.2021.108417

APA

Dhawan, V., Joshi, G., Sutariya, B., Shah, J., Ashtikar, M., Nagarsekar, K., Steiniger, F., Lokras, A., Fahr, A., Krishnapriya, M., Warawdekar, U., Saraf, M., & Nagarsenker, M. (2021). Polysaccharide conjugates surpass monosaccharide ligands in hepatospecific targeting – Synthesis and comparative in silico and in vitro assessment. Carbohydrate Research, 509, [108417]. https://doi.org/10.1016/j.carres.2021.108417

Vancouver

Dhawan V, Joshi G, Sutariya B, Shah J, Ashtikar M, Nagarsekar K et al. Polysaccharide conjugates surpass monosaccharide ligands in hepatospecific targeting – Synthesis and comparative in silico and in vitro assessment. Carbohydrate Research. 2021;509. 108417. https://doi.org/10.1016/j.carres.2021.108417

Author

Dhawan, V. ; Joshi, G. ; Sutariya, B. ; Shah, J. ; Ashtikar, M. ; Nagarsekar, K. ; Steiniger, F. ; Lokras, A. ; Fahr, A. ; Krishnapriya, M. ; Warawdekar, U. ; Saraf, M. ; Nagarsenker, M. / Polysaccharide conjugates surpass monosaccharide ligands in hepatospecific targeting – Synthesis and comparative in silico and in vitro assessment. In: Carbohydrate Research. 2021 ; Vol. 509.

Bibtex

@article{c1c24c099fbd42f28b91d2ffba1861e0,
title = "Polysaccharide conjugates surpass monosaccharide ligands in hepatospecific targeting – Synthesis and comparative in silico and in vitro assessment",
abstract = "Ligands with the polysaccharide headgroups have been recently reported by our group to possess enhanced interaction with asialoglycoprotein receptor (ASGPR) in silico as compared to ligands having galactose moieties. This enhanced interaction is a result of the polymer's backbone support in anchoring the ligand in a specific orientation within the bilayer. In this paper, we have attempted to provide an in vitro proof of concept by performing a comparative evaluation of polysaccharide and monosaccharide-based ligands. Docking was performed to understand interaction with ASGPR in silico. Agarose and galactose conjugates with behenic acid were synthesized, purified, and characterized to yield biocompatible hepatospecific ligands which were incorporated into nanoliposomes. Cellular internalization of these targeted liposomes was studied using confocal microscopy and flow cytometry. The toxicity potential was assessed in vivo. Results indicated that the polysaccharide-based ligand increased cellular uptake due to better interaction with the receptor as compared to ligand bearing a single galactose group. In addition to developing novel liver targeting ligands, the study also established proof of concept that has been suggested by earlier in silico investigations. The approach can be used to design targeting ligands and develop formulations with improved targeting efficacy.",
keywords = "Agarose, Behenic acid, Biocompatible ligands, Galactose, Liposomes, Liver, Polysaccharides, Targeting",
author = "V. Dhawan and G. Joshi and B. Sutariya and J. Shah and M. Ashtikar and K. Nagarsekar and F. Steiniger and A. Lokras and A. Fahr and M. Krishnapriya and U. Warawdekar and M. Saraf and M. Nagarsenker",
note = "Publisher Copyright: {\textcopyright} 2021 Elsevier Ltd",
year = "2021",
doi = "10.1016/j.carres.2021.108417",
language = "English",
volume = "509",
journal = "Carbohydrate Research",
issn = "0008-6215",
publisher = "Pergamon Press",

}

RIS

TY - JOUR

T1 - Polysaccharide conjugates surpass monosaccharide ligands in hepatospecific targeting – Synthesis and comparative in silico and in vitro assessment

AU - Dhawan, V.

AU - Joshi, G.

AU - Sutariya, B.

AU - Shah, J.

AU - Ashtikar, M.

AU - Nagarsekar, K.

AU - Steiniger, F.

AU - Lokras, A.

AU - Fahr, A.

AU - Krishnapriya, M.

AU - Warawdekar, U.

AU - Saraf, M.

AU - Nagarsenker, M.

N1 - Publisher Copyright: © 2021 Elsevier Ltd

PY - 2021

Y1 - 2021

N2 - Ligands with the polysaccharide headgroups have been recently reported by our group to possess enhanced interaction with asialoglycoprotein receptor (ASGPR) in silico as compared to ligands having galactose moieties. This enhanced interaction is a result of the polymer's backbone support in anchoring the ligand in a specific orientation within the bilayer. In this paper, we have attempted to provide an in vitro proof of concept by performing a comparative evaluation of polysaccharide and monosaccharide-based ligands. Docking was performed to understand interaction with ASGPR in silico. Agarose and galactose conjugates with behenic acid were synthesized, purified, and characterized to yield biocompatible hepatospecific ligands which were incorporated into nanoliposomes. Cellular internalization of these targeted liposomes was studied using confocal microscopy and flow cytometry. The toxicity potential was assessed in vivo. Results indicated that the polysaccharide-based ligand increased cellular uptake due to better interaction with the receptor as compared to ligand bearing a single galactose group. In addition to developing novel liver targeting ligands, the study also established proof of concept that has been suggested by earlier in silico investigations. The approach can be used to design targeting ligands and develop formulations with improved targeting efficacy.

AB - Ligands with the polysaccharide headgroups have been recently reported by our group to possess enhanced interaction with asialoglycoprotein receptor (ASGPR) in silico as compared to ligands having galactose moieties. This enhanced interaction is a result of the polymer's backbone support in anchoring the ligand in a specific orientation within the bilayer. In this paper, we have attempted to provide an in vitro proof of concept by performing a comparative evaluation of polysaccharide and monosaccharide-based ligands. Docking was performed to understand interaction with ASGPR in silico. Agarose and galactose conjugates with behenic acid were synthesized, purified, and characterized to yield biocompatible hepatospecific ligands which were incorporated into nanoliposomes. Cellular internalization of these targeted liposomes was studied using confocal microscopy and flow cytometry. The toxicity potential was assessed in vivo. Results indicated that the polysaccharide-based ligand increased cellular uptake due to better interaction with the receptor as compared to ligand bearing a single galactose group. In addition to developing novel liver targeting ligands, the study also established proof of concept that has been suggested by earlier in silico investigations. The approach can be used to design targeting ligands and develop formulations with improved targeting efficacy.

KW - Agarose

KW - Behenic acid

KW - Biocompatible ligands

KW - Galactose

KW - Liposomes

KW - Liver

KW - Polysaccharides

KW - Targeting

U2 - 10.1016/j.carres.2021.108417

DO - 10.1016/j.carres.2021.108417

M3 - Journal article

C2 - 34481155

AN - SCOPUS:85113952921

VL - 509

JO - Carbohydrate Research

JF - Carbohydrate Research

SN - 0008-6215

M1 - 108417

ER -

ID: 280290753