| アイテムタイプ |
学術雑誌論文 / Journal Article(1) |
| 公開日 |
2023-08-07 |
| タイトル |
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タイトル |
Multiplexed Imaging Reveals the Spatial Relationship of the Extracellular Acidity-Targeting pHLIP with Necrosis, Hypoxia, and the Integrin-Targeting cRGD Peptide |
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言語 |
en |
| 言語 |
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言語 |
eng |
| 資源タイプ |
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資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
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資源タイプ |
journal article |
| 著者 |
Zhao-Hui Jin
Tsuji Atsushi
Melissa Degardin
Pascal Dumy
Didier Boturyn
Higashi Tatsuya
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| 抄録 |
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内容記述タイプ |
Abstract |
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内容記述 |
pH (low) insertion peptides (pHLIPs) have been developed for cancer imaging and therapy targeting the acidic extracellular microenvironment. However, the characteristics of intratumoral distribution (ITD) of pHLIPs are not yet fully understood. This study aimed to reveal the details of the ITD of pHLIPs and their spatial relationship with other tumor features of concern. The fluorescent dye-labeled pHLIPs were intravenously administered to subcutaneous xenograft mouse models of U87MG and IGR-OV1 expressing αVβ3 integrins (using large necrotic tumors). The αVβ3 integrin-targeting Cy5.5-RAFT-c(-RGDfK-)4 was used as a reference. In vivo and ex vivo fluorescence imaging, whole-tumor section imaging, fluorescence microscopy, and multiplexed fluorescence colocalization analysis were performed. The ITD of fluorescent dye-labeled pHLIPs was heterogeneous, having a high degree of colocalization with necrosis. A direct one-to-one comparison of highly magnified images revealed the cellular localization of pHLIP in pyknotic, karyorrhexis, and karyolytic necrotic cells. pHLIP and hypoxia were spatially contiguous but not overlapping cellularly. The hypoxic region was found between the ITDs of pHLIP and the cRGD peptide and the Ki-67 proliferative activity remained detectable in the pHLIP-accumulated regions. The results provide a better understanding of the characteristics of ITD of pHLIPs, leading to new insights into the theranostic applications of pHLIPs. |
| 書誌情報 |
Cells
巻 11,
号 21,
p. 3499,
発行日 2022-11
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| 出版者 |
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出版者 |
MDPI |
| ISSN |
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収録物識別子タイプ |
ISSN |
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収録物識別子 |
2073-4409 |
| PubMed番号 |
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識別子タイプ |
PMID |
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関連識別子 |
36359894 |
| DOI |
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識別子タイプ |
DOI |
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関連識別子 |
10.3390/cells11213499 |
