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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Main Authors: Jay K. Bhattarai, Dharmendra Neupane, Bishal Nepal, Alexei V. Demchenko, Keith J. Stine
Format: Article
Language:English
Published: MDPI AG 2021-01-01
Series:Nanomaterials
Subjects:
Online Access:https://www.mdpi.com/2079-4991/11/1/208
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author Jay K. Bhattarai
Dharmendra Neupane
Bishal Nepal
Alexei V. Demchenko
Keith J. Stine
author_facet Jay K. Bhattarai
Dharmendra Neupane
Bishal Nepal
Alexei V. Demchenko
Keith J. Stine
author_sort Jay K. Bhattarai
collection DOAJ
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<sup>−3</sup> 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 doaj.art-4f574ec7504f4b1289e032d1f61cc6bb2023-12-03T13:18:16ZengMDPI AGNanomaterials2079-49912021-01-0111120810.3390/nano11010208Nanoporous Gold Monolith for High Loading of Unmodified Doxorubicin and Sustained Co-Release of Doxorubicin-RapamycinJay K. Bhattarai0Dharmendra Neupane1Bishal Nepal2Alexei V. Demchenko3Keith J. Stine4Department of Chemistry and Biochemistry, University of Missouri—St. Louis, Saint Louis, MO 63121, USADepartment of Chemistry and Biochemistry, University of Missouri—St. Louis, Saint Louis, MO 63121, USADepartment of Chemistry and Biochemistry, University of Missouri—St. Louis, Saint Louis, MO 63121, USADepartment of Chemistry and Biochemistry, University of Missouri—St. Louis, Saint Louis, MO 63121, USADepartment of Chemistry and Biochemistry, University of Missouri—St. Louis, Saint Louis, MO 63121, USANanoparticles (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<sup>−3</sup> 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.https://www.mdpi.com/2079-4991/11/1/208nanoporous goldimplantdoxorubicinrapamycinsustained drug release
spellingShingle Jay K. Bhattarai
Dharmendra Neupane
Bishal Nepal
Alexei V. Demchenko
Keith J. Stine
Nanoporous Gold Monolith for High Loading of Unmodified Doxorubicin and Sustained Co-Release of Doxorubicin-Rapamycin
Nanomaterials
nanoporous gold
implant
doxorubicin
rapamycin
sustained drug release
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 nanoporous gold
implant
doxorubicin
rapamycin
sustained drug release
url https://www.mdpi.com/2079-4991/11/1/208
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