Intracellular NO-Releasing Hyaluronic Acid-Based Nanocarriers: A Potential Chemosensitizing Agent for Cancer Chemotherapy

In this work, we investigate whether S-nitrosoglutathione (GSNO)-conjugated hyaluronic acid-based self-assembled nanoparticles (GSNO-HANPs) can be useful as a chemosensitizing agent to improve the anticancer activity of doxorubicin (DOX). The GSNO-HANPs were prepared by aqueous assembly of GSNO-conj...

Full description

Saved in:
Bibliographic Details
Published in:ACS applied materials & interfaces 2018-08, Vol.10 (32), p.26870-26881
Main Authors: Kim, Da Eun, Kim, Chan Woo, Lee, Hong Jae, Min, Kyung Hyun, Kwack, Kyu Hwan, Lee, Hyeon-Woo, Bang, Jaebeum, Chang, Kiyuk, Lee, Sang Cheon
Format: Article
Language:English
Subjects:
Animals
Cytoplasm
Doxorubicin
Drug Delivery Systems
Humans
Hyaluronic Acid - chemistry
MCF-7 Cells
Nanoparticles
Nitric Oxide
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:In this work, we investigate whether S-nitrosoglutathione (GSNO)-conjugated hyaluronic acid-based self-assembled nanoparticles (GSNO-HANPs) can be useful as a chemosensitizing agent to improve the anticancer activity of doxorubicin (DOX). The GSNO-HANPs were prepared by aqueous assembly of GSNO-conjugated HA with grafted poly­(lactide-co-glycolide). Aqueous GSNO stability shielded within the assembled environments of the GSNO-HANPs was greatly enhanced, compared to that of free GSNO. The NO release from the GSNO-HANPs was facilitated in the presence of hyaluronidase-1 (Hyal-1) and ascorbic acid at intracellular concentrations. Microscopic analysis showed GSNO-HANPs effectively generated NO within the cells. We observed that NO made the human MCF-7 breast cancer cells vulnerable to DOX. This chemosensitizing activity was supported by the observation of an increased level of ONOO– (peroxynitrite), a highly reactive oxygen species, upon co-treatment with the GSNO-HANPs and DOX. Apoptosis assays showed that GSNO-HANP alone exhibited negligible cytotoxic effects and reinforced apoptotic activity of DOX. Animal experiments demonstrated the effective accumulation of GSNO-HANPs in solid MCF-7 tumors and effectively suppressed tumor growth in combination with DOX. This hyaluronic acid-based intracellularly NO-releasing nanoparticles may serve as a significant chemosensitizing agent in treatments of various cancers.
ISSN:1944-8244
1944-8252
DOI:10.1021/acsami.8b06848