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Development of pH-Responsive Hyaluronic Acid-Conjugated Cyclodextrin Nanoparticles for Chemo-/CO-Gas Dual Therapy

In this study, we fabricated γ-cyclodextrin (γCD)-based nanoparticles (NPs) for dual antitumor therapy. First, γCD (the backbone biopolymer) was chemically conjugated with low-molecular-weight hyaluronic acid (HA; a tumoral CD44 receptor-targeting molecule) and 3-(diethylamino)propylamine (DEAP; a p...

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Autores principales: Lee, Eunsol, Lee, Eun Seong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10384822/
https://www.ncbi.nlm.nih.gov/pubmed/37514005
http://dx.doi.org/10.3390/pharmaceutics15071818
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author Lee, Eunsol
Lee, Eun Seong
author_facet Lee, Eunsol
Lee, Eun Seong
author_sort Lee, Eunsol
collection PubMed
description In this study, we fabricated γ-cyclodextrin (γCD)-based nanoparticles (NPs) for dual antitumor therapy. First, γCD (the backbone biopolymer) was chemically conjugated with low-molecular-weight hyaluronic acid (HA; a tumoral CD44 receptor-targeting molecule) and 3-(diethylamino)propylamine (DEAP; a pH-responsive molecule), termed as γCD-(DEAP/HA). The obtained γCD-(DEAP/HA) self-assembled in aqueous solution, producing the γCD-(DEAP/HA) NPs. These NPs efficiently entrapped paclitaxel (PTX; an antitumor drug) and triiron dodecacarbonyl (FeCO; an endogenous cytotoxic gas molecule) via hydrophobic interactions between PTX and FeCO with the unprotonated DEAP molecules in γCD-(DEAP/HA) and a possible host–guest interaction in the γCD rings. The release of PTX and FeCO from the NPs resulted from particle destabilization at endosomal pH, probably owing to the protonation of DEAP in the NPs. In vitro studies using MCF-7 tumor cells demonstrated that these NPs were efficiently internalized by the cells expressing CD44 receptors and enhanced PTX/FeCO-mediated tumor cell apoptosis. Importantly, local light irradiation of FeCO stimulated the generation of cytotoxic CO, resulting in highly improved tumor cell death. We expect that these NPs have potential as dual-modal therapeutic candidates with enhanced antitumor activity in response to acidic pH and local light irradiation.
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spelling pubmed-103848222023-07-30 Development of pH-Responsive Hyaluronic Acid-Conjugated Cyclodextrin Nanoparticles for Chemo-/CO-Gas Dual Therapy Lee, Eunsol Lee, Eun Seong Pharmaceutics Article In this study, we fabricated γ-cyclodextrin (γCD)-based nanoparticles (NPs) for dual antitumor therapy. First, γCD (the backbone biopolymer) was chemically conjugated with low-molecular-weight hyaluronic acid (HA; a tumoral CD44 receptor-targeting molecule) and 3-(diethylamino)propylamine (DEAP; a pH-responsive molecule), termed as γCD-(DEAP/HA). The obtained γCD-(DEAP/HA) self-assembled in aqueous solution, producing the γCD-(DEAP/HA) NPs. These NPs efficiently entrapped paclitaxel (PTX; an antitumor drug) and triiron dodecacarbonyl (FeCO; an endogenous cytotoxic gas molecule) via hydrophobic interactions between PTX and FeCO with the unprotonated DEAP molecules in γCD-(DEAP/HA) and a possible host–guest interaction in the γCD rings. The release of PTX and FeCO from the NPs resulted from particle destabilization at endosomal pH, probably owing to the protonation of DEAP in the NPs. In vitro studies using MCF-7 tumor cells demonstrated that these NPs were efficiently internalized by the cells expressing CD44 receptors and enhanced PTX/FeCO-mediated tumor cell apoptosis. Importantly, local light irradiation of FeCO stimulated the generation of cytotoxic CO, resulting in highly improved tumor cell death. We expect that these NPs have potential as dual-modal therapeutic candidates with enhanced antitumor activity in response to acidic pH and local light irradiation. MDPI 2023-06-25 /pmc/articles/PMC10384822/ /pubmed/37514005 http://dx.doi.org/10.3390/pharmaceutics15071818 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lee, Eunsol
Lee, Eun Seong
Development of pH-Responsive Hyaluronic Acid-Conjugated Cyclodextrin Nanoparticles for Chemo-/CO-Gas Dual Therapy
title Development of pH-Responsive Hyaluronic Acid-Conjugated Cyclodextrin Nanoparticles for Chemo-/CO-Gas Dual Therapy
title_full Development of pH-Responsive Hyaluronic Acid-Conjugated Cyclodextrin Nanoparticles for Chemo-/CO-Gas Dual Therapy
title_fullStr Development of pH-Responsive Hyaluronic Acid-Conjugated Cyclodextrin Nanoparticles for Chemo-/CO-Gas Dual Therapy
title_full_unstemmed Development of pH-Responsive Hyaluronic Acid-Conjugated Cyclodextrin Nanoparticles for Chemo-/CO-Gas Dual Therapy
title_short Development of pH-Responsive Hyaluronic Acid-Conjugated Cyclodextrin Nanoparticles for Chemo-/CO-Gas Dual Therapy
title_sort development of ph-responsive hyaluronic acid-conjugated cyclodextrin nanoparticles for chemo-/co-gas dual therapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10384822/
https://www.ncbi.nlm.nih.gov/pubmed/37514005
http://dx.doi.org/10.3390/pharmaceutics15071818
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