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Galactose-based Thermosensitive Nanogels for Targeted Drug Delivery of Iodoazomycin Arabinofuranoside (IAZA) for Theranostic Management of Hypoxic Hepatocellular Carcinoma.
Biomacromolecules. 2015 Jul 13; 16(7):1978-86.B

Abstract

In this study, galactose-based nanogels were prepared by reversible addition-fragmentation chain transfer process to facilitate the targeted delivery of iodoazomycin arabinofuranoside (IAZA), a clinical drug for imaging solid hypoxic tumors, and evaluate its role in hypoxia-selective (radio)theranostic (therapy + diagnostic) management of therapy-resistant cancer cells. The nanogels have a cross-linked temperature-responsive core and a dense carbohydrate shell. Their thermoresponsive nature allowed the controlled encapsulation of IAZA drug for targeted delivery and release in hypoxic hepatocellular carcinoma via asialoglycoprotein receptor-mediated uptake. The synthesized nanogel-IAZA delivery systems demonstrated a stable, nonburst release of IAZA over 10 h with up to 0.6 mM loading capacity of IAZA within the nanogel. The cytotoxicity evaluations of the nanogels demonstrated that they are relatively nontoxic in multiple cell lines. The radiosensitization studies indicated that IAZA in encapsulated form offers a superior radiosensitization of hypoxic cells (sensitizer enhancement ratio for IAZA alone, 1.33; 1.62 for nanogel encapsulated IAZA). These studies suggest that galactose-based nanogels may serve as a versatile drug delivery system for IAZA (and other azomycin-based agents) and enable its hypoxia-selective multimodal theranostic applications to manage hypoxic solid (hepatocellular) tumors by facilitating position/single photon emission tomography-based imaging, external beam radiation therapy, and in situ molecular radiotherapy.

Authors+Show Affiliations

†Department of Chemical and Materials Engineering, University of Alberta, 116 Street and 85th Avenue, Edmonton T6G 2G6, Alberta, Canada.†Department of Chemical and Materials Engineering, University of Alberta, 116 Street and 85th Avenue, Edmonton T6G 2G6, Alberta, Canada.No affiliation info availableNo affiliation info available†Department of Chemical and Materials Engineering, University of Alberta, 116 Street and 85th Avenue, Edmonton T6G 2G6, Alberta, Canada.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25996799

Citation

Quan, Stephen, et al. "Galactose-based Thermosensitive Nanogels for Targeted Drug Delivery of Iodoazomycin Arabinofuranoside (IAZA) for Theranostic Management of Hypoxic Hepatocellular Carcinoma." Biomacromolecules, vol. 16, no. 7, 2015, pp. 1978-86.
Quan S, Wang Y, Zhou A, et al. Galactose-based Thermosensitive Nanogels for Targeted Drug Delivery of Iodoazomycin Arabinofuranoside (IAZA) for Theranostic Management of Hypoxic Hepatocellular Carcinoma. Biomacromolecules. 2015;16(7):1978-86.
Quan, S., Wang, Y., Zhou, A., Kumar, P., & Narain, R. (2015). Galactose-based Thermosensitive Nanogels for Targeted Drug Delivery of Iodoazomycin Arabinofuranoside (IAZA) for Theranostic Management of Hypoxic Hepatocellular Carcinoma. Biomacromolecules, 16(7), 1978-86. https://doi.org/10.1021/acs.biomac.5b00576
Quan S, et al. Galactose-based Thermosensitive Nanogels for Targeted Drug Delivery of Iodoazomycin Arabinofuranoside (IAZA) for Theranostic Management of Hypoxic Hepatocellular Carcinoma. Biomacromolecules. 2015 Jul 13;16(7):1978-86. PubMed PMID: 25996799.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Galactose-based Thermosensitive Nanogels for Targeted Drug Delivery of Iodoazomycin Arabinofuranoside (IAZA) for Theranostic Management of Hypoxic Hepatocellular Carcinoma. AU - Quan,Stephen, AU - Wang,Yinan, AU - Zhou,Aihua, AU - Kumar,Piyush, AU - Narain,Ravin, Y1 - 2015/06/03/ PY - 2015/5/22/entrez PY - 2015/5/23/pubmed PY - 2016/4/28/medline SP - 1978 EP - 86 JF - Biomacromolecules JO - Biomacromolecules VL - 16 IS - 7 N2 - In this study, galactose-based nanogels were prepared by reversible addition-fragmentation chain transfer process to facilitate the targeted delivery of iodoazomycin arabinofuranoside (IAZA), a clinical drug for imaging solid hypoxic tumors, and evaluate its role in hypoxia-selective (radio)theranostic (therapy + diagnostic) management of therapy-resistant cancer cells. The nanogels have a cross-linked temperature-responsive core and a dense carbohydrate shell. Their thermoresponsive nature allowed the controlled encapsulation of IAZA drug for targeted delivery and release in hypoxic hepatocellular carcinoma via asialoglycoprotein receptor-mediated uptake. The synthesized nanogel-IAZA delivery systems demonstrated a stable, nonburst release of IAZA over 10 h with up to 0.6 mM loading capacity of IAZA within the nanogel. The cytotoxicity evaluations of the nanogels demonstrated that they are relatively nontoxic in multiple cell lines. The radiosensitization studies indicated that IAZA in encapsulated form offers a superior radiosensitization of hypoxic cells (sensitizer enhancement ratio for IAZA alone, 1.33; 1.62 for nanogel encapsulated IAZA). These studies suggest that galactose-based nanogels may serve as a versatile drug delivery system for IAZA (and other azomycin-based agents) and enable its hypoxia-selective multimodal theranostic applications to manage hypoxic solid (hepatocellular) tumors by facilitating position/single photon emission tomography-based imaging, external beam radiation therapy, and in situ molecular radiotherapy. SN - 1526-4602 UR - https://www.unboundmedicine.com/medline/citation/25996799/Galactose_based_Thermosensitive_Nanogels_for_Targeted_Drug_Delivery_of_Iodoazomycin_Arabinofuranoside__IAZA__for_Theranostic_Management_of_Hypoxic_Hepatocellular_Carcinoma_ L2 - https://dx.doi.org/10.1021/acs.biomac.5b00576 DB - PRIME DP - Unbound Medicine ER -