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Glycopolymer-Functionalized MOF-808 Nanoparticles as a Cancer-Targeted Dual Drug Delivery System for Carboplatin and Floxuridine
[Image: see text] Codelivery of chemotherapeutics via nanomaterials has attracted much attention over the last decades due to improved drug delivery to tumor tissues, decreased systemic effects, and increased therapeutic efficacies. High porosities, large pore volumes and surface areas, and tunable...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9623548/ https://www.ncbi.nlm.nih.gov/pubmed/36338327 http://dx.doi.org/10.1021/acsanm.2c01632 |
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author | Demir Duman, Fatma Monaco, Alessandra Foulkes, Rachel Becer, C. Remzi Forgan, Ross S. |
author_facet | Demir Duman, Fatma Monaco, Alessandra Foulkes, Rachel Becer, C. Remzi Forgan, Ross S. |
author_sort | Demir Duman, Fatma |
collection | PubMed |
description | [Image: see text] Codelivery of chemotherapeutics via nanomaterials has attracted much attention over the last decades due to improved drug delivery to tumor tissues, decreased systemic effects, and increased therapeutic efficacies. High porosities, large pore volumes and surface areas, and tunable structures have positioned metal–organic frameworks (MOFs) as promising drug delivery systems (DDSs). In particular, nanoscale Zr-linked MOFs such as MOF-808 offer notable advantages for biomedical applications such as high porosity, good stability, and biocompatibility. In this study, we report efficient dual drug delivery of floxuridine (FUDR) and carboplatin (CARB) loaded in MOF-808 nanoparticles to cancer cells. The nanoparticles were further functionalized by a poly(acrylic acid-mannose acrylamide) (PAAMAM) glycopolymer coating to obtain a highly selective DDS in cancer cells and enhance the therapeutic efficacy of chemotherapy. While MOF-808 was found to enhance the individual therapeutic effects of FUDR and CARB toward cancerous cells, combining FUDR and CARB was seen to cause a synergistic effect, further enhancing the cytotoxicity of the free drugs. Enhancement of CARB loading and therefore cytotoxicity of the CARB-loaded MOFs could be induced through a modified activation protocol, while coating of MOF-808 with the PAAMAM glycopolymer increased the uptake of the nanoparticles in cancer cells used in the study and offered a particularly significant selective drug delivery with high cytotoxicity in HepG2 human hepatocellular carcinoma cells. These results show how the enhancement of cytotoxicity is possible through both nanovector delivery and synergistic treatment, and that MOF-808 is a viable candidate for future drug delivery studies. |
format | Online Article Text |
id | pubmed-9623548 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-96235482022-11-02 Glycopolymer-Functionalized MOF-808 Nanoparticles as a Cancer-Targeted Dual Drug Delivery System for Carboplatin and Floxuridine Demir Duman, Fatma Monaco, Alessandra Foulkes, Rachel Becer, C. Remzi Forgan, Ross S. ACS Appl Nano Mater [Image: see text] Codelivery of chemotherapeutics via nanomaterials has attracted much attention over the last decades due to improved drug delivery to tumor tissues, decreased systemic effects, and increased therapeutic efficacies. High porosities, large pore volumes and surface areas, and tunable structures have positioned metal–organic frameworks (MOFs) as promising drug delivery systems (DDSs). In particular, nanoscale Zr-linked MOFs such as MOF-808 offer notable advantages for biomedical applications such as high porosity, good stability, and biocompatibility. In this study, we report efficient dual drug delivery of floxuridine (FUDR) and carboplatin (CARB) loaded in MOF-808 nanoparticles to cancer cells. The nanoparticles were further functionalized by a poly(acrylic acid-mannose acrylamide) (PAAMAM) glycopolymer coating to obtain a highly selective DDS in cancer cells and enhance the therapeutic efficacy of chemotherapy. While MOF-808 was found to enhance the individual therapeutic effects of FUDR and CARB toward cancerous cells, combining FUDR and CARB was seen to cause a synergistic effect, further enhancing the cytotoxicity of the free drugs. Enhancement of CARB loading and therefore cytotoxicity of the CARB-loaded MOFs could be induced through a modified activation protocol, while coating of MOF-808 with the PAAMAM glycopolymer increased the uptake of the nanoparticles in cancer cells used in the study and offered a particularly significant selective drug delivery with high cytotoxicity in HepG2 human hepatocellular carcinoma cells. These results show how the enhancement of cytotoxicity is possible through both nanovector delivery and synergistic treatment, and that MOF-808 is a viable candidate for future drug delivery studies. American Chemical Society 2022-06-22 2022-10-28 /pmc/articles/PMC9623548/ /pubmed/36338327 http://dx.doi.org/10.1021/acsanm.2c01632 Text en © 2022 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Demir Duman, Fatma Monaco, Alessandra Foulkes, Rachel Becer, C. Remzi Forgan, Ross S. Glycopolymer-Functionalized MOF-808 Nanoparticles as a Cancer-Targeted Dual Drug Delivery System for Carboplatin and Floxuridine |
title | Glycopolymer-Functionalized MOF-808 Nanoparticles
as a Cancer-Targeted Dual Drug Delivery System for Carboplatin and
Floxuridine |
title_full | Glycopolymer-Functionalized MOF-808 Nanoparticles
as a Cancer-Targeted Dual Drug Delivery System for Carboplatin and
Floxuridine |
title_fullStr | Glycopolymer-Functionalized MOF-808 Nanoparticles
as a Cancer-Targeted Dual Drug Delivery System for Carboplatin and
Floxuridine |
title_full_unstemmed | Glycopolymer-Functionalized MOF-808 Nanoparticles
as a Cancer-Targeted Dual Drug Delivery System for Carboplatin and
Floxuridine |
title_short | Glycopolymer-Functionalized MOF-808 Nanoparticles
as a Cancer-Targeted Dual Drug Delivery System for Carboplatin and
Floxuridine |
title_sort | glycopolymer-functionalized mof-808 nanoparticles
as a cancer-targeted dual drug delivery system for carboplatin and
floxuridine |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9623548/ https://www.ncbi.nlm.nih.gov/pubmed/36338327 http://dx.doi.org/10.1021/acsanm.2c01632 |
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