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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

Preliminary safety evaluation of the nanoprobe. Cell viability studies in HUVEC cells (A) and 293T cells (B). (C) The change of the body weight over the regimen. (D) The organ coefficients after treatment. (E) Histological examination of heart, liver, spleen, lung, and kidney. The nanoprobe caused little changes in the organs, while the QD-MPA induced severe toxicity.
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Figure 9: Preliminary safety evaluation of the nanoprobe. Cell viability studies in HUVEC cells (A) and 293T cells (B). (C) The change of the body weight over the regimen. (D) The organ coefficients after treatment. (E) Histological examination of heart, liver, spleen, lung, and kidney. The nanoprobe caused little changes in the organs, while the QD-MPA induced severe toxicity.

Mentions: The biocompatibility of the nanoprobe was investigated in non-tumoral 293T and HUVEC cell lines. The results showed that LMWH modification remarkably improved the biocompatibility of QD; the prepared nanoprobes exhibited a dose-dependent inhibitory effect on cell growth, and cell viability at 250 μg/mL was all above 70% (Figure 9A&B). Of note, the dose for in vivo imaging was far much less than that.


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)

Preliminary safety evaluation of the nanoprobe. Cell viability studies in HUVEC cells (A) and 293T cells (B). (C) The change of the body weight over the regimen. (D) The organ coefficients after treatment. (E) Histological examination of heart, liver, spleen, lung, and kidney. The nanoprobe caused little changes in the organs, while the QD-MPA induced severe toxicity.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 9: Preliminary safety evaluation of the nanoprobe. Cell viability studies in HUVEC cells (A) and 293T cells (B). (C) The change of the body weight over the regimen. (D) The organ coefficients after treatment. (E) Histological examination of heart, liver, spleen, lung, and kidney. The nanoprobe caused little changes in the organs, while the QD-MPA induced severe toxicity.
Mentions: The biocompatibility of the nanoprobe was investigated in non-tumoral 293T and HUVEC cell lines. The results showed that LMWH modification remarkably improved the biocompatibility of QD; the prepared nanoprobes exhibited a dose-dependent inhibitory effect on cell growth, and cell viability at 250 μg/mL was all above 70% (Figure 9A&B). Of note, the dose for in vivo imaging was far much less than that.

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