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A Prodrug-type, MMP-2-targeting Nanoprobe for Tumor Detection and Imaging.

Wang Y, Lin T, Zhang W, Jiang Y, Jin H, He H, Yang VC, Chen Y, Huang Y - Theranostics (2015)

Bottom Line: As a case in point, expression of matrix metalloproteases (MMP) is significantly up-regulated in tumorigenesis, invasion, and metastasis among a majority of cancers.The T7-functionalized nanoprobe is capable of detecting the orthotopic brain tumor, with clear, real-time in vivo imaging.This method is promising for in vivo detection of brain tumor, and real-time monitor of a TAP (i.e., MMP-2).

View Article: PubMed Central - PubMed

Affiliation: 1. Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin 300070, China. ; 2. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Hai-ke Rd, Shanghai 201203, China.

ABSTRACT
Tumor-associated proteases (TAPs) have been intensively studied because of their critical roles in cancer development. As a case in point, expression of matrix metalloproteases (MMP) is significantly up-regulated in tumorigenesis, invasion, and metastasis among a majority of cancers. Here we present a prodrug-type, MMP-2-responsive nanoprobe system with high efficiency and low toxicity for detecting MMP-2-overexpressed tumors. The nanoprobe system is featured by its self-assembled fabrication and FRET effect. This prodrug-type nanoprobe is selectively activated by MMP-2, and thus useful for detection of the MMP-2-overexpressed cells and tumors. The nanoprobe system works successfully in various animal tumor models, including human fibrosarcoma and subcutaneous glioma xenograft. Furthermore, in order to overcome the blood brain barrier (BBB) and achieve brain tumor targeting, a transferrin-receptor targeting peptide (T7 peptide) is strategically incorporated into the nanoprobe. The T7-functionalized nanoprobe is capable of detecting the orthotopic brain tumor, with clear, real-time in vivo imaging. This method is promising for in vivo detection of brain tumor, and real-time monitor of a TAP (i.e., MMP-2).

No MeSH data available.


Related in: MedlinePlus

(A) The orthotopic glioma imaging with the T7-functionalized nanoprobe at various time points. (B) The radiant efficiency (fluorescence intensity).
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Figure 8: (A) The orthotopic glioma imaging with the T7-functionalized nanoprobe at various time points. (B) The radiant efficiency (fluorescence intensity).

Mentions: However, the in vivo detection of brain tumor is severely impeded by poor penetration through the BBB of the probes. The subcutaneous glioma xenograft model is not sufficient to reflect the clinical conditions. We thus employed the orthotopic glioma mouse model. The development of orthotopic glioma xenograft (U87-Luc cell line) was confirmed by giving luciferin substrate (Figure 8A, left panel). The brain-targeting T7 sequence was incorporated into the ALMWP so as to improve the accumulation of the nanoprobe in the brain tumor. The T7-functionalized nanoprobe was administered via tail vein injection. The nanoprobe was activated in the brain tumor quickly (within 1 h). The orthotopic brain tumor was clearly detected, indicating the ability to penetrate through the BBB and target to the glioma cells, as well as the efficient activation by the overexpressed MMP-2 at tumor. The fluorescence gradually increased in 10 h, and was found a declination at 22 h. By contrast, the nanoprobe without T7 modification showed very minor effect presumably due to its insufficient efficiency of brain delivery (data not shown). Furthermore, the orthotopic xenograft was processed with cryosection, the activated nanoprobes were found in the tumor (Supplementary Material: Figure S5).


A Prodrug-type, MMP-2-targeting Nanoprobe for Tumor Detection and Imaging.

Wang Y, Lin T, Zhang W, Jiang Y, Jin H, He H, Yang VC, Chen Y, Huang Y - Theranostics (2015)

(A) The orthotopic glioma imaging with the T7-functionalized nanoprobe at various time points. (B) The radiant efficiency (fluorescence intensity).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4440437&req=5

Figure 8: (A) The orthotopic glioma imaging with the T7-functionalized nanoprobe at various time points. (B) The radiant efficiency (fluorescence intensity).
Mentions: However, the in vivo detection of brain tumor is severely impeded by poor penetration through the BBB of the probes. The subcutaneous glioma xenograft model is not sufficient to reflect the clinical conditions. We thus employed the orthotopic glioma mouse model. The development of orthotopic glioma xenograft (U87-Luc cell line) was confirmed by giving luciferin substrate (Figure 8A, left panel). The brain-targeting T7 sequence was incorporated into the ALMWP so as to improve the accumulation of the nanoprobe in the brain tumor. The T7-functionalized nanoprobe was administered via tail vein injection. The nanoprobe was activated in the brain tumor quickly (within 1 h). The orthotopic brain tumor was clearly detected, indicating the ability to penetrate through the BBB and target to the glioma cells, as well as the efficient activation by the overexpressed MMP-2 at tumor. The fluorescence gradually increased in 10 h, and was found a declination at 22 h. By contrast, the nanoprobe without T7 modification showed very minor effect presumably due to its insufficient efficiency of brain delivery (data not shown). Furthermore, the orthotopic xenograft was processed with cryosection, the activated nanoprobes were found in the tumor (Supplementary Material: Figure S5).

Bottom Line: As a case in point, expression of matrix metalloproteases (MMP) is significantly up-regulated in tumorigenesis, invasion, and metastasis among a majority of cancers.The T7-functionalized nanoprobe is capable of detecting the orthotopic brain tumor, with clear, real-time in vivo imaging.This method is promising for in vivo detection of brain tumor, and real-time monitor of a TAP (i.e., MMP-2).

View Article: PubMed Central - PubMed

Affiliation: 1. Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin 300070, China. ; 2. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Hai-ke Rd, Shanghai 201203, China.

ABSTRACT
Tumor-associated proteases (TAPs) have been intensively studied because of their critical roles in cancer development. As a case in point, expression of matrix metalloproteases (MMP) is significantly up-regulated in tumorigenesis, invasion, and metastasis among a majority of cancers. Here we present a prodrug-type, MMP-2-responsive nanoprobe system with high efficiency and low toxicity for detecting MMP-2-overexpressed tumors. The nanoprobe system is featured by its self-assembled fabrication and FRET effect. This prodrug-type nanoprobe is selectively activated by MMP-2, and thus useful for detection of the MMP-2-overexpressed cells and tumors. The nanoprobe system works successfully in various animal tumor models, including human fibrosarcoma and subcutaneous glioma xenograft. Furthermore, in order to overcome the blood brain barrier (BBB) and achieve brain tumor targeting, a transferrin-receptor targeting peptide (T7 peptide) is strategically incorporated into the nanoprobe. The T7-functionalized nanoprobe is capable of detecting the orthotopic brain tumor, with clear, real-time in vivo imaging. This method is promising for in vivo detection of brain tumor, and real-time monitor of a TAP (i.e., MMP-2).

No MeSH data available.


Related in: MedlinePlus