Tumor-Targeting Glycol Chitosan Nanoparticles for Image-Guided Surgery of Rabbit Orthotopic VX2 Lung Cancer
Theranostic nanoparticles can deliver therapeutic agents as well as diverse imaging agents to tumors. The enhanced permeation and retention (EPR) effect is regarded as a crucial mechanism for the tumor-targeted delivery of nanoparticles. Although a large number of studies of the EPR effect of theran...
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| Format: | Article |
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MDPI AG
2020-07-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/12/7/621 |
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| author | Kyeong Cheol On Jiyun Rho Hong Yeol Yoon Hyeyoun Chang Ji Young Yhee Jun Sik Yoon Seo Young Jeong Hyun Koo Kim Kwangmeyung Kim |
| author_facet | Kyeong Cheol On Jiyun Rho Hong Yeol Yoon Hyeyoun Chang Ji Young Yhee Jun Sik Yoon Seo Young Jeong Hyun Koo Kim Kwangmeyung Kim |
| author_sort | Kyeong Cheol On |
| collection | DOAJ |
| description | Theranostic nanoparticles can deliver therapeutic agents as well as diverse imaging agents to tumors. The enhanced permeation and retention (EPR) effect is regarded as a crucial mechanism for the tumor-targeted delivery of nanoparticles. Although a large number of studies of the EPR effect of theranostic nanoparticles have been performed, the effect of the change in the body size of the host on the EPR effect is not fully understood. In this regard, comparative research is needed on the behavior of nanoparticles in large animals for developing the nanoparticles to the clinical stage. In this study, we prepared fluorophore (indocyanine green (ICG) or cyanine 5.5 (Cy5.5))–conjugated glycol chitosan nanoparticles (CNPs) for comparing the tumor-targeting efficacy in VX2 tumor-bearing mouse and rabbit models. As expected, the CNPs formed nano-sized spherical nanoparticles and were stable for 8 days under aqueous conditions. The CNPs also exhibited dose-dependent cellular uptake into VX2 tumor cells without cytotoxicity. The half-life of the near-infrared fluorescence (NIRF) signals in the blood were 3.25 h and 4.73 h when the CNPs were injected into mice and rabbits, respectively. Importantly, the CNPs showed excellent tumor accumulation and prolonged biodistribution profiles in both the VX2 tumor-bearing mouse and rabbit models, wherein the tumor accumulation was maximized at 48 h and 72 h, respectively. Based on the excellent tumor accumulation of the CNPs, finally, the CNPs were used in the image-guided surgery of the rabbit orthotopic VX2 lung tumor model. The lung tumor tissue was successfully removed based on the NIRF signal from the CNPs in the tumor tissue. This study shows that CNPs can be potentially used for tumor theragnosis in small animals and large animals. |
| first_indexed | 2024-03-10T18:42:08Z |
| format | Article |
| id | doaj.art-07856020de324683adf976df5c29bb74 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T18:42:08Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-07856020de324683adf976df5c29bb742023-11-20T05:45:22ZengMDPI AGPharmaceutics1999-49232020-07-0112762110.3390/pharmaceutics12070621Tumor-Targeting Glycol Chitosan Nanoparticles for Image-Guided Surgery of Rabbit Orthotopic VX2 Lung CancerKyeong Cheol On0Jiyun Rho1Hong Yeol Yoon2Hyeyoun Chang3Ji Young Yhee4Jun Sik Yoon5Seo Young Jeong6Hyun Koo Kim7Kwangmeyung Kim8Department of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul 02447, KoreaDepartment of Biomedical Sciences, College of Medicine, Korea University, Seoul 02841, KoreaCenter for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, KoreaDepartment of Cancer Biology, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA 02215, USAPharosgen Co. Seoul 05505, KoreaDepartment of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul 02447, KoreaDepartment of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul 02447, KoreaDepartment of Biomedical Sciences, College of Medicine, Korea University, Seoul 02841, KoreaCenter for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, KoreaTheranostic nanoparticles can deliver therapeutic agents as well as diverse imaging agents to tumors. The enhanced permeation and retention (EPR) effect is regarded as a crucial mechanism for the tumor-targeted delivery of nanoparticles. Although a large number of studies of the EPR effect of theranostic nanoparticles have been performed, the effect of the change in the body size of the host on the EPR effect is not fully understood. In this regard, comparative research is needed on the behavior of nanoparticles in large animals for developing the nanoparticles to the clinical stage. In this study, we prepared fluorophore (indocyanine green (ICG) or cyanine 5.5 (Cy5.5))–conjugated glycol chitosan nanoparticles (CNPs) for comparing the tumor-targeting efficacy in VX2 tumor-bearing mouse and rabbit models. As expected, the CNPs formed nano-sized spherical nanoparticles and were stable for 8 days under aqueous conditions. The CNPs also exhibited dose-dependent cellular uptake into VX2 tumor cells without cytotoxicity. The half-life of the near-infrared fluorescence (NIRF) signals in the blood were 3.25 h and 4.73 h when the CNPs were injected into mice and rabbits, respectively. Importantly, the CNPs showed excellent tumor accumulation and prolonged biodistribution profiles in both the VX2 tumor-bearing mouse and rabbit models, wherein the tumor accumulation was maximized at 48 h and 72 h, respectively. Based on the excellent tumor accumulation of the CNPs, finally, the CNPs were used in the image-guided surgery of the rabbit orthotopic VX2 lung tumor model. The lung tumor tissue was successfully removed based on the NIRF signal from the CNPs in the tumor tissue. This study shows that CNPs can be potentially used for tumor theragnosis in small animals and large animals.https://www.mdpi.com/1999-4923/12/7/621glycol chitosan nanoparticleimage-guided surgerytumor-targeted delivery |
| spellingShingle | Kyeong Cheol On Jiyun Rho Hong Yeol Yoon Hyeyoun Chang Ji Young Yhee Jun Sik Yoon Seo Young Jeong Hyun Koo Kim Kwangmeyung Kim Tumor-Targeting Glycol Chitosan Nanoparticles for Image-Guided Surgery of Rabbit Orthotopic VX2 Lung Cancer Pharmaceutics glycol chitosan nanoparticle image-guided surgery tumor-targeted delivery |
| title | Tumor-Targeting Glycol Chitosan Nanoparticles for Image-Guided Surgery of Rabbit Orthotopic VX2 Lung Cancer |
| title_full | Tumor-Targeting Glycol Chitosan Nanoparticles for Image-Guided Surgery of Rabbit Orthotopic VX2 Lung Cancer |
| title_fullStr | Tumor-Targeting Glycol Chitosan Nanoparticles for Image-Guided Surgery of Rabbit Orthotopic VX2 Lung Cancer |
| title_full_unstemmed | Tumor-Targeting Glycol Chitosan Nanoparticles for Image-Guided Surgery of Rabbit Orthotopic VX2 Lung Cancer |
| title_short | Tumor-Targeting Glycol Chitosan Nanoparticles for Image-Guided Surgery of Rabbit Orthotopic VX2 Lung Cancer |
| title_sort | tumor targeting glycol chitosan nanoparticles for image guided surgery of rabbit orthotopic vx2 lung cancer |
| topic | glycol chitosan nanoparticle image-guided surgery tumor-targeted delivery |
| url | https://www.mdpi.com/1999-4923/12/7/621 |
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