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Nanoporous Gold Monolith for High Loading of Unmodified Doxorubicin and Sustained Co-Release of Doxorubicin-Rapamycin

Nanoparticles (NPs) have been widely explored for delivering doxorubicin (DOX), an anticancer drug, to minimize cardiotoxicity. However, their efficiency is marred by a necessity to chemically modify DOX, NPs, or both and low deposition of the administered NPs on tumors. Therefore, alternative strat...

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Autores principales: Bhattarai, Jay K., Neupane, Dharmendra, Nepal, Bishal, Demchenko, Alexei V., Stine, Keith J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830488/
https://www.ncbi.nlm.nih.gov/pubmed/33467416
http://dx.doi.org/10.3390/nano11010208
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author Bhattarai, Jay K.
Neupane, Dharmendra
Nepal, Bishal
Demchenko, Alexei V.
Stine, Keith J.
author_facet Bhattarai, Jay K.
Neupane, Dharmendra
Nepal, Bishal
Demchenko, Alexei V.
Stine, Keith J.
author_sort Bhattarai, Jay K.
collection PubMed
description Nanoparticles (NPs) have been widely explored for delivering doxorubicin (DOX), an anticancer drug, to minimize cardiotoxicity. However, their efficiency is marred by a necessity to chemically modify DOX, NPs, or both and low deposition of the administered NPs on tumors. Therefore, alternative strategies should be developed to improve therapeutic efficacy and decrease toxicity. Here we report the possibility of employing a monolithic nanoporous gold (np-Au) rod as an implant for delivering DOX. The np-Au has very high DOX encapsulation efficiency (>98%) with maximum loading of 93.4 mg cm(−3) without any chemical modification required of DOX or np-Au. We provide a plausible mechanism for the high loading of DOX in np-Au. The DOX sustained release for 26 days from np-Au in different pH conditions at 37 °C, which was monitored using UV-Vis spectroscopy. Additionally, we encased the DOX-loaded np-Au with rapamycin (RAPA)-trapped poly(D,L-lactide-co-glycolide) (PLGA) to fabricate an np-Au@PLGA/RAPA implant and optimized the combinatorial release of DOX and RAPA. Further exploiting the effect of the protein corona around np-Au and np-Au@PLGA/RAPA showed zero-order release kinetics of DOX. This work proves that the np-Au-based implant has the potential to be used as a DOX carrier of potential use in cancer treatment.
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spelling pubmed-78304882021-01-26 Nanoporous Gold Monolith for High Loading of Unmodified Doxorubicin and Sustained Co-Release of Doxorubicin-Rapamycin Bhattarai, Jay K. Neupane, Dharmendra Nepal, Bishal Demchenko, Alexei V. Stine, Keith J. Nanomaterials (Basel) Article Nanoparticles (NPs) have been widely explored for delivering doxorubicin (DOX), an anticancer drug, to minimize cardiotoxicity. However, their efficiency is marred by a necessity to chemically modify DOX, NPs, or both and low deposition of the administered NPs on tumors. Therefore, alternative strategies should be developed to improve therapeutic efficacy and decrease toxicity. Here we report the possibility of employing a monolithic nanoporous gold (np-Au) rod as an implant for delivering DOX. The np-Au has very high DOX encapsulation efficiency (>98%) with maximum loading of 93.4 mg cm(−3) without any chemical modification required of DOX or np-Au. We provide a plausible mechanism for the high loading of DOX in np-Au. The DOX sustained release for 26 days from np-Au in different pH conditions at 37 °C, which was monitored using UV-Vis spectroscopy. Additionally, we encased the DOX-loaded np-Au with rapamycin (RAPA)-trapped poly(D,L-lactide-co-glycolide) (PLGA) to fabricate an np-Au@PLGA/RAPA implant and optimized the combinatorial release of DOX and RAPA. Further exploiting the effect of the protein corona around np-Au and np-Au@PLGA/RAPA showed zero-order release kinetics of DOX. This work proves that the np-Au-based implant has the potential to be used as a DOX carrier of potential use in cancer treatment. MDPI 2021-01-15 /pmc/articles/PMC7830488/ /pubmed/33467416 http://dx.doi.org/10.3390/nano11010208 Text en © 2021 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bhattarai, Jay K.
Neupane, Dharmendra
Nepal, Bishal
Demchenko, Alexei V.
Stine, Keith J.
Nanoporous Gold Monolith for High Loading of Unmodified Doxorubicin and Sustained Co-Release of Doxorubicin-Rapamycin
title Nanoporous Gold Monolith for High Loading of Unmodified Doxorubicin and Sustained Co-Release of Doxorubicin-Rapamycin
title_full Nanoporous Gold Monolith for High Loading of Unmodified Doxorubicin and Sustained Co-Release of Doxorubicin-Rapamycin
title_fullStr Nanoporous Gold Monolith for High Loading of Unmodified Doxorubicin and Sustained Co-Release of Doxorubicin-Rapamycin
title_full_unstemmed Nanoporous Gold Monolith for High Loading of Unmodified Doxorubicin and Sustained Co-Release of Doxorubicin-Rapamycin
title_short Nanoporous Gold Monolith for High Loading of Unmodified Doxorubicin and Sustained Co-Release of Doxorubicin-Rapamycin
title_sort nanoporous gold monolith for high loading of unmodified doxorubicin and sustained co-release of doxorubicin-rapamycin
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830488/
https://www.ncbi.nlm.nih.gov/pubmed/33467416
http://dx.doi.org/10.3390/nano11010208
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