Cargando…
Lysinated Multiwalled Carbon Nanotubes with Carbohydrate Ligands as an Effective Nanocarrier for Targeted Doxorubicin Delivery to Breast Cancer Cells
Multiwalled carbon nanotubes (MWCNTs) are elongated, hollow cylindrical nanotubes made of sp2 carbon. MWCNTs have attracted significant attention in the area of drug delivery due to their high drug-loading capacity and large surface area. Furthermore, they can be linked to bioactive ligands molecule...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9657689/ https://www.ncbi.nlm.nih.gov/pubmed/36364286 http://dx.doi.org/10.3390/molecules27217461 |
_version_ | 1784829760212303872 |
---|---|
author | Thakur, Chanchal Kiran Neupane, Rabin Karthikeyan, Chandrabose Ashby, Charles R. Babu, R. Jayachandra Boddu, Sai H. S. Tiwari, Amit K. Moorthy, Narayana Subbiah Hari Narayana |
author_facet | Thakur, Chanchal Kiran Neupane, Rabin Karthikeyan, Chandrabose Ashby, Charles R. Babu, R. Jayachandra Boddu, Sai H. S. Tiwari, Amit K. Moorthy, Narayana Subbiah Hari Narayana |
author_sort | Thakur, Chanchal Kiran |
collection | PubMed |
description | Multiwalled carbon nanotubes (MWCNTs) are elongated, hollow cylindrical nanotubes made of sp2 carbon. MWCNTs have attracted significant attention in the area of drug delivery due to their high drug-loading capacity and large surface area. Furthermore, they can be linked to bioactive ligands molecules via covalent and noncovalent bonds that allow for the targeted delivery of anticancer drugs such as doxorubicin. The majority of methodologies reported for the functionalization of MWCNTs for drug delivery are quite complex and use expensive linkers and ligands. In the present study, we report a simple, cost-effective approach for functionalizing MWCNTs with the carbohydrate ligands, galactose (GA), mannose (MA) and lactose (LA), using lysine as a linker. The doxorubicin (Dox)-loaded functionalized MWCNTs were characterized using FT-IR, NMR, Raman, XRD and FE-SEM. The drug–loaded MWCNTs were evaluated for drug loading, drug release and cell toxicity in vitro, in breast cancer cells. The results indicated that the carbohydrate-modified lysinated MWCNTs had greater Dox loading capacity, compared to carboxylated MWCNTs (COOHMWCNTs) and lysinated MWCNTs (LyMWCNTs). In vitro drug release experiments indicated that the carbohydrate functionalized LyMWCNTs had higher Dox release at pH 5.0, compared to the physiological pH of 7.4, over 120 h, indicating that they are suitable candidates for targeting the tumor microenvironment as a result of their sustained release profile of Dox. Doxorubicin-loaded galactosylated MWCNTs (Dox-GAMWCNTs) and doxorubicin loaded mannosylated MWCNTs (Dox-MAMWCNTs) had greater anticancer efficacy and cellular uptake, compared to doxorubicin–loaded lactosylated MWCNTs (Dox-LAMWCNTs) and pure Dox, in MDA-MB231 and MCF7 breast cancer cells. However, neither the ligand conjugated multiwall blank carbon nanotubes (GAMWCNTs, MAMWCNTs and LAMWCNTs) nor the lysinated multiwalled blank carbon nanotubes produced significant toxicity in the normal cells. Our results suggest that sugar-tethered multiwalled carbon nanotubes, especially the galactosylated (Dox-GAMWCNTs) and mannosylated (Dox-MAMWCNTs) formulations, may be used to improve the targeted delivery of anticancer drugs to breast cancer cells. |
format | Online Article Text |
id | pubmed-9657689 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-96576892022-11-15 Lysinated Multiwalled Carbon Nanotubes with Carbohydrate Ligands as an Effective Nanocarrier for Targeted Doxorubicin Delivery to Breast Cancer Cells Thakur, Chanchal Kiran Neupane, Rabin Karthikeyan, Chandrabose Ashby, Charles R. Babu, R. Jayachandra Boddu, Sai H. S. Tiwari, Amit K. Moorthy, Narayana Subbiah Hari Narayana Molecules Article Multiwalled carbon nanotubes (MWCNTs) are elongated, hollow cylindrical nanotubes made of sp2 carbon. MWCNTs have attracted significant attention in the area of drug delivery due to their high drug-loading capacity and large surface area. Furthermore, they can be linked to bioactive ligands molecules via covalent and noncovalent bonds that allow for the targeted delivery of anticancer drugs such as doxorubicin. The majority of methodologies reported for the functionalization of MWCNTs for drug delivery are quite complex and use expensive linkers and ligands. In the present study, we report a simple, cost-effective approach for functionalizing MWCNTs with the carbohydrate ligands, galactose (GA), mannose (MA) and lactose (LA), using lysine as a linker. The doxorubicin (Dox)-loaded functionalized MWCNTs were characterized using FT-IR, NMR, Raman, XRD and FE-SEM. The drug–loaded MWCNTs were evaluated for drug loading, drug release and cell toxicity in vitro, in breast cancer cells. The results indicated that the carbohydrate-modified lysinated MWCNTs had greater Dox loading capacity, compared to carboxylated MWCNTs (COOHMWCNTs) and lysinated MWCNTs (LyMWCNTs). In vitro drug release experiments indicated that the carbohydrate functionalized LyMWCNTs had higher Dox release at pH 5.0, compared to the physiological pH of 7.4, over 120 h, indicating that they are suitable candidates for targeting the tumor microenvironment as a result of their sustained release profile of Dox. Doxorubicin-loaded galactosylated MWCNTs (Dox-GAMWCNTs) and doxorubicin loaded mannosylated MWCNTs (Dox-MAMWCNTs) had greater anticancer efficacy and cellular uptake, compared to doxorubicin–loaded lactosylated MWCNTs (Dox-LAMWCNTs) and pure Dox, in MDA-MB231 and MCF7 breast cancer cells. However, neither the ligand conjugated multiwall blank carbon nanotubes (GAMWCNTs, MAMWCNTs and LAMWCNTs) nor the lysinated multiwalled blank carbon nanotubes produced significant toxicity in the normal cells. Our results suggest that sugar-tethered multiwalled carbon nanotubes, especially the galactosylated (Dox-GAMWCNTs) and mannosylated (Dox-MAMWCNTs) formulations, may be used to improve the targeted delivery of anticancer drugs to breast cancer cells. MDPI 2022-11-02 /pmc/articles/PMC9657689/ /pubmed/36364286 http://dx.doi.org/10.3390/molecules27217461 Text en © 2022 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 Thakur, Chanchal Kiran Neupane, Rabin Karthikeyan, Chandrabose Ashby, Charles R. Babu, R. Jayachandra Boddu, Sai H. S. Tiwari, Amit K. Moorthy, Narayana Subbiah Hari Narayana Lysinated Multiwalled Carbon Nanotubes with Carbohydrate Ligands as an Effective Nanocarrier for Targeted Doxorubicin Delivery to Breast Cancer Cells |
title | Lysinated Multiwalled Carbon Nanotubes with Carbohydrate Ligands as an Effective Nanocarrier for Targeted Doxorubicin Delivery to Breast Cancer Cells |
title_full | Lysinated Multiwalled Carbon Nanotubes with Carbohydrate Ligands as an Effective Nanocarrier for Targeted Doxorubicin Delivery to Breast Cancer Cells |
title_fullStr | Lysinated Multiwalled Carbon Nanotubes with Carbohydrate Ligands as an Effective Nanocarrier for Targeted Doxorubicin Delivery to Breast Cancer Cells |
title_full_unstemmed | Lysinated Multiwalled Carbon Nanotubes with Carbohydrate Ligands as an Effective Nanocarrier for Targeted Doxorubicin Delivery to Breast Cancer Cells |
title_short | Lysinated Multiwalled Carbon Nanotubes with Carbohydrate Ligands as an Effective Nanocarrier for Targeted Doxorubicin Delivery to Breast Cancer Cells |
title_sort | lysinated multiwalled carbon nanotubes with carbohydrate ligands as an effective nanocarrier for targeted doxorubicin delivery to breast cancer cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9657689/ https://www.ncbi.nlm.nih.gov/pubmed/36364286 http://dx.doi.org/10.3390/molecules27217461 |
work_keys_str_mv | AT thakurchanchalkiran lysinatedmultiwalledcarbonnanotubeswithcarbohydrateligandsasaneffectivenanocarrierfortargeteddoxorubicindeliverytobreastcancercells AT neupanerabin lysinatedmultiwalledcarbonnanotubeswithcarbohydrateligandsasaneffectivenanocarrierfortargeteddoxorubicindeliverytobreastcancercells AT karthikeyanchandrabose lysinatedmultiwalledcarbonnanotubeswithcarbohydrateligandsasaneffectivenanocarrierfortargeteddoxorubicindeliverytobreastcancercells AT ashbycharlesr lysinatedmultiwalledcarbonnanotubeswithcarbohydrateligandsasaneffectivenanocarrierfortargeteddoxorubicindeliverytobreastcancercells AT baburjayachandra lysinatedmultiwalledcarbonnanotubeswithcarbohydrateligandsasaneffectivenanocarrierfortargeteddoxorubicindeliverytobreastcancercells AT boddusaihs lysinatedmultiwalledcarbonnanotubeswithcarbohydrateligandsasaneffectivenanocarrierfortargeteddoxorubicindeliverytobreastcancercells AT tiwariamitk lysinatedmultiwalledcarbonnanotubeswithcarbohydrateligandsasaneffectivenanocarrierfortargeteddoxorubicindeliverytobreastcancercells AT moorthynarayanasubbiahharinarayana lysinatedmultiwalledcarbonnanotubeswithcarbohydrateligandsasaneffectivenanocarrierfortargeteddoxorubicindeliverytobreastcancercells |