Mesenchymal Stem Cell-Mediated Deep Tumor Delivery of Gold Nanorod for Photothermal Therapy
Gold nanoparticles (AuNPs) with various sizes and morphologies have been extensively investigated for effective photothermal therapy (PTT) against multiple cancer types. However, a highly dynamic and complex tumor microenvironment (TME) considerably reduces the efficacy of PTT by limiting deep tumor...
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MDPI AG
2022-09-01
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| Series: | Nanomaterials |
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| Online Access: | https://www.mdpi.com/2079-4991/12/19/3410 |
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| author | Wan Su Yun Man Kyu Shim Seungho Lim Sukyung Song Jinseong Kim Suah Yang Hee Sook Hwang Mi Ra Kim Hong Yeol Yoon Dong-Kwon Lim In-Cheol Sun Kwangmeyung Kim |
| author_facet | Wan Su Yun Man Kyu Shim Seungho Lim Sukyung Song Jinseong Kim Suah Yang Hee Sook Hwang Mi Ra Kim Hong Yeol Yoon Dong-Kwon Lim In-Cheol Sun Kwangmeyung Kim |
| author_sort | Wan Su Yun |
| collection | DOAJ |
| description | Gold nanoparticles (AuNPs) with various sizes and morphologies have been extensively investigated for effective photothermal therapy (PTT) against multiple cancer types. However, a highly dynamic and complex tumor microenvironment (TME) considerably reduces the efficacy of PTT by limiting deep tumor penetration of AuNPs. Herein, we propose a mesenchymal stem cell (MSC)-mediated deep tumor delivery of gold nanorod (AuNR) for a potent PTT. First, MSCs are treated with tetraacylated N-azidomannosamine (Ac<sub>4</sub>ManNAz) to introduce modifiable azide (N<sub>3</sub>) groups on the cell surface via metabolic glycoengineering. Then, AuNRs modified with bio-orthogonal click molecules of bicyclo[6.1.0]nonyne (AuNR@BCN) are chemically conjugated to the N<sub>3</sub> groups on the MSC surface by copper-free click chemistry reaction, resulting in AuNR@MSCs. In cultured MSCs, the appropriate condition to incorporate the AuNR into the MSCs is optimized; in addition, the photothermal efficiency of AuNR-MSCs under light irradiation are assessed, showing efficient heat generation in vitro. In colon tumor-bearing mice, intravenously injected AuNR@MSCs efficiently accumulate within the tumor tissues by allowing deep tissue penetration owing to the tumor homing effect by natural tumor tropism of AuNR@MSCs. Upon localized light irradiation, the AuNR@MSCs significantly inhibit colon tumor growth by the enhanced photothermal effect compared to conventional AuNRs. Collectively, this study shows a promising approach of MSCs-mediated deep tumor delivery of AuNR for effective PTT. |
| first_indexed | 2024-03-09T21:21:32Z |
| format | Article |
| id | doaj.art-2c30dbc9b7d3401380b321a33fe20e19 |
| institution | Directory Open Access Journal |
| issn | 2079-4991 |
| language | English |
| last_indexed | 2024-03-09T21:21:32Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Nanomaterials |
| spelling | doaj.art-2c30dbc9b7d3401380b321a33fe20e192023-11-23T21:19:37ZengMDPI AGNanomaterials2079-49912022-09-011219341010.3390/nano12193410Mesenchymal Stem Cell-Mediated Deep Tumor Delivery of Gold Nanorod for Photothermal TherapyWan Su Yun0Man Kyu Shim1Seungho Lim2Sukyung Song3Jinseong Kim4Suah Yang5Hee Sook Hwang6Mi Ra Kim7Hong Yeol Yoon8Dong-Kwon Lim9In-Cheol Sun10Kwangmeyung Kim11KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul 02841, KoreaBiomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, KoreaBiomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, KoreaBiomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, KoreaKU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul 02841, KoreaKU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul 02841, KoreaDepartment of Pharmaceutical Engineering, Dankook University, Cheonan 31116, KoreaDepartment of Otorhinolaryngology-Head and Neck Surgery, Haeundae Paik Hospital, Inje University College of Medicine, Busan 48108, KoreaBiomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, KoreaKU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul 02841, KoreaBiomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, KoreaKU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul 02841, KoreaGold nanoparticles (AuNPs) with various sizes and morphologies have been extensively investigated for effective photothermal therapy (PTT) against multiple cancer types. However, a highly dynamic and complex tumor microenvironment (TME) considerably reduces the efficacy of PTT by limiting deep tumor penetration of AuNPs. Herein, we propose a mesenchymal stem cell (MSC)-mediated deep tumor delivery of gold nanorod (AuNR) for a potent PTT. First, MSCs are treated with tetraacylated N-azidomannosamine (Ac<sub>4</sub>ManNAz) to introduce modifiable azide (N<sub>3</sub>) groups on the cell surface via metabolic glycoengineering. Then, AuNRs modified with bio-orthogonal click molecules of bicyclo[6.1.0]nonyne (AuNR@BCN) are chemically conjugated to the N<sub>3</sub> groups on the MSC surface by copper-free click chemistry reaction, resulting in AuNR@MSCs. In cultured MSCs, the appropriate condition to incorporate the AuNR into the MSCs is optimized; in addition, the photothermal efficiency of AuNR-MSCs under light irradiation are assessed, showing efficient heat generation in vitro. In colon tumor-bearing mice, intravenously injected AuNR@MSCs efficiently accumulate within the tumor tissues by allowing deep tissue penetration owing to the tumor homing effect by natural tumor tropism of AuNR@MSCs. Upon localized light irradiation, the AuNR@MSCs significantly inhibit colon tumor growth by the enhanced photothermal effect compared to conventional AuNRs. Collectively, this study shows a promising approach of MSCs-mediated deep tumor delivery of AuNR for effective PTT.https://www.mdpi.com/2079-4991/12/19/3410mesenchymal stem cellgold nanoroddrug deliverydeep tumor penetrationphotothermal therapy |
| spellingShingle | Wan Su Yun Man Kyu Shim Seungho Lim Sukyung Song Jinseong Kim Suah Yang Hee Sook Hwang Mi Ra Kim Hong Yeol Yoon Dong-Kwon Lim In-Cheol Sun Kwangmeyung Kim Mesenchymal Stem Cell-Mediated Deep Tumor Delivery of Gold Nanorod for Photothermal Therapy Nanomaterials mesenchymal stem cell gold nanorod drug delivery deep tumor penetration photothermal therapy |
| title | Mesenchymal Stem Cell-Mediated Deep Tumor Delivery of Gold Nanorod for Photothermal Therapy |
| title_full | Mesenchymal Stem Cell-Mediated Deep Tumor Delivery of Gold Nanorod for Photothermal Therapy |
| title_fullStr | Mesenchymal Stem Cell-Mediated Deep Tumor Delivery of Gold Nanorod for Photothermal Therapy |
| title_full_unstemmed | Mesenchymal Stem Cell-Mediated Deep Tumor Delivery of Gold Nanorod for Photothermal Therapy |
| title_short | Mesenchymal Stem Cell-Mediated Deep Tumor Delivery of Gold Nanorod for Photothermal Therapy |
| title_sort | mesenchymal stem cell mediated deep tumor delivery of gold nanorod for photothermal therapy |
| topic | mesenchymal stem cell gold nanorod drug delivery deep tumor penetration photothermal therapy |
| url | https://www.mdpi.com/2079-4991/12/19/3410 |
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