Surface peptide functionalization of zeolitic imidazolate framework-8 for autonomous homing and enhanced delivery of chemotherapeutic agent to lung tumor cells
Chemotherapeutic agents used in treating certain cancer types operate in a non-selective manner tending to accumulate in normal, healthy tissue when high doses are used. To mitigate the toxicity effect resulting from this, there is an urgent need to develop active nano delivery systems capable of re...
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| Format: | Article |
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Royal Society of Chemistry
2021
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| author | Mohd Abdul Kamal, Nurul Akmarina Abdulmalek, Emilia Fakurazi, Sharida Cordova, Kyle E. Abdul Rahman, Mohd Basyaruddin |
| author_facet | Mohd Abdul Kamal, Nurul Akmarina Abdulmalek, Emilia Fakurazi, Sharida Cordova, Kyle E. Abdul Rahman, Mohd Basyaruddin |
| author_sort | Mohd Abdul Kamal, Nurul Akmarina |
| collection | UPM |
| description | Chemotherapeutic agents used in treating certain cancer types operate in a non-selective manner tending to accumulate in normal, healthy tissue when high doses are used. To mitigate the toxicity effect resulting from this, there is an urgent need to develop active nano delivery systems capable of regulating optimal doses specifically to cancer cells without harming adjacent normal cells. Herein, we report a versatile nanoparticle – zeolitic imidazolate framework-8 (nZIF-8) – that is loaded with a chemotherapeutic agent (gemcitabine; GEM) and surface-functionalized with an autonomous homing system (Arg-Gly-Asp peptide ligand; RGD) via a straightforward, one-pot solvothermal reaction. Successful functionalization of the surface of nZIF-8 loaded GEM (GEM⊂nZIF-8) with RGD was proven by spectroscopic and electron microscopy techniques. This surface-functionalized nanoparticle (GEM⊂RGD@nZIF-8) exhibited enhanced uptake in human lung cancer cells (A549), compared with non-functionalized GEM⊂nZIF-8. The GEM⊂RGD@nZIF-8, experienced not only efficient uptake within A549, but also induced obvious cytotoxicity (75% at a concentration of 10 μg mL−1) and apoptosis (62%) after 48 h treatment when compared to the nanoparticle absent of the RGD homing system (GEM⊂nZIF-8). Most importantly, this surface-functionalized nanoparticle was more selective towards lung cancer cells (A549) than normal human lung fibroblast cells (MRC-5) with a selectivity index (SI) of 3.98. This work demonstrates a new one-pot strategy for realizing a surface-functionalized zeolitic imidazolate framework that actively targets cancer cells via an autonomous homing peptide system to deliver a chemotherapeutic payload effectively. |
| first_indexed | 2024-03-06T11:00:58Z |
| format | Article |
| id | upm.eprints-95219 |
| institution | Universiti Putra Malaysia |
| last_indexed | 2024-03-06T11:00:58Z |
| publishDate | 2021 |
| publisher | Royal Society of Chemistry |
| record_format | dspace |
| spelling | upm.eprints-952192023-04-07T01:59:42Z http://psasir.upm.edu.my/id/eprint/95219/ Surface peptide functionalization of zeolitic imidazolate framework-8 for autonomous homing and enhanced delivery of chemotherapeutic agent to lung tumor cells Mohd Abdul Kamal, Nurul Akmarina Abdulmalek, Emilia Fakurazi, Sharida Cordova, Kyle E. Abdul Rahman, Mohd Basyaruddin Chemotherapeutic agents used in treating certain cancer types operate in a non-selective manner tending to accumulate in normal, healthy tissue when high doses are used. To mitigate the toxicity effect resulting from this, there is an urgent need to develop active nano delivery systems capable of regulating optimal doses specifically to cancer cells without harming adjacent normal cells. Herein, we report a versatile nanoparticle – zeolitic imidazolate framework-8 (nZIF-8) – that is loaded with a chemotherapeutic agent (gemcitabine; GEM) and surface-functionalized with an autonomous homing system (Arg-Gly-Asp peptide ligand; RGD) via a straightforward, one-pot solvothermal reaction. Successful functionalization of the surface of nZIF-8 loaded GEM (GEM⊂nZIF-8) with RGD was proven by spectroscopic and electron microscopy techniques. This surface-functionalized nanoparticle (GEM⊂RGD@nZIF-8) exhibited enhanced uptake in human lung cancer cells (A549), compared with non-functionalized GEM⊂nZIF-8. The GEM⊂RGD@nZIF-8, experienced not only efficient uptake within A549, but also induced obvious cytotoxicity (75% at a concentration of 10 μg mL−1) and apoptosis (62%) after 48 h treatment when compared to the nanoparticle absent of the RGD homing system (GEM⊂nZIF-8). Most importantly, this surface-functionalized nanoparticle was more selective towards lung cancer cells (A549) than normal human lung fibroblast cells (MRC-5) with a selectivity index (SI) of 3.98. This work demonstrates a new one-pot strategy for realizing a surface-functionalized zeolitic imidazolate framework that actively targets cancer cells via an autonomous homing peptide system to deliver a chemotherapeutic payload effectively. Royal Society of Chemistry 2021-02-02 Article PeerReviewed Mohd Abdul Kamal, Nurul Akmarina and Abdulmalek, Emilia and Fakurazi, Sharida and Cordova, Kyle E. and Abdul Rahman, Mohd Basyaruddin (2021) Surface peptide functionalization of zeolitic imidazolate framework-8 for autonomous homing and enhanced delivery of chemotherapeutic agent to lung tumor cells. Dalton Transactions, 50 (7). pp. 2375-2386. ISSN 1477-9226; ESSN: 1477-9234 https://pubs.rsc.org/en/content/articlelanding/2021/dt/d1dt00116g 10.1039/d1dt00116g |
| spellingShingle | Mohd Abdul Kamal, Nurul Akmarina Abdulmalek, Emilia Fakurazi, Sharida Cordova, Kyle E. Abdul Rahman, Mohd Basyaruddin Surface peptide functionalization of zeolitic imidazolate framework-8 for autonomous homing and enhanced delivery of chemotherapeutic agent to lung tumor cells |
| title | Surface peptide functionalization of zeolitic imidazolate framework-8 for autonomous homing and enhanced delivery of chemotherapeutic agent to lung tumor cells |
| title_full | Surface peptide functionalization of zeolitic imidazolate framework-8 for autonomous homing and enhanced delivery of chemotherapeutic agent to lung tumor cells |
| title_fullStr | Surface peptide functionalization of zeolitic imidazolate framework-8 for autonomous homing and enhanced delivery of chemotherapeutic agent to lung tumor cells |
| title_full_unstemmed | Surface peptide functionalization of zeolitic imidazolate framework-8 for autonomous homing and enhanced delivery of chemotherapeutic agent to lung tumor cells |
| title_short | Surface peptide functionalization of zeolitic imidazolate framework-8 for autonomous homing and enhanced delivery of chemotherapeutic agent to lung tumor cells |
| title_sort | surface peptide functionalization of zeolitic imidazolate framework 8 for autonomous homing and enhanced delivery of chemotherapeutic agent to lung tumor cells |
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