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Published on: December 15, 2010
Construction of ultrasonic nanobubbles carrying CAIX polypeptides to target carcinoma cells derived from various
Lianhua Zhu1, Yanli Guo2, Luofu Wang3
1Department of Ultrasound, Southwest Hospital, Third Military Medical University, 30 Gaotanyan Street, Shapingba District, Chongqing, 400038, China.
Background:
Ultrasound molecular imaging is a novel diagnostic approach for tumors, whose key link is the construction of targeted ultrasound contrast agents. However, available targeted ultrasound contrast agents for molecular imaging of tumors are only achieving imaging in blood pool or one type tumor. No targeted ultrasound contrast agents have realized targeted ultrasound molecular imaging of tumor parenchymal cells in a variety of solid tumors so far. Carbonic anhydrase IX (CAIX) is highly expressed on cell membranes of various malignant solid tumors, so it's a good target for ultrasound molecular imaging. Here, targeted nanobubbles carrying CAIX polypeptides for targeted binding to a variety of malignant tumors were constructed, and targeted binding ability and ultrasound imaging effect in different types of tumors were evaluated.
Results:
The mean diameter of lipid targeted nanobubbles was (503.7 ± 78.47) nm, and the polypeptides evenly distributed on the surfaces of targeted nanobubbles, which possessed the advantages of homogenous particle size, high stability, and good safety. Targeted nanobubbles could gather around CAIX-positive cells (786-O and Hela cells), while they cannot gather around CAIX-negative cells (BxPC-3 cells) in vitro, and the affinity of targeted nanobubbles to CAIX-positive cells were significantly higher than that to CAIX-negative cells (P < 0.05). Peak intensity and duration time of targeted nanobubbles and blank nanobubbles were different in CAIX-positive transplanted tumor tissues in vivo (P < 0.05). Moreover, targeted nanobubbles in CAIX-positive transplanted tumor tissues produced higher peak intensity and longer duration time than those in CAIX-negative transplanted tumor tissues (P < 0.05). Finally, immunofluorescence not only confirmed targeted nanobubbles could pass through blood vessels to enter in tumor tissue spaces, but also clarified imaging differences of targeted nanobubbles in different types of transplanted tumor tissues.
Conclusions:
Targeted nanobubbles carrying CAIX polypeptides can specifically enhance ultrasound imaging in CAIX-positive transplanted tumor tissues and could potentially be used in early diagnosis of a variety of solid tumors derived from various organs.
Insights
New targeted nanobubbles carrying carbonic anhydrase IX (CAIX) polypeptides enable specific ultrasound molecular imaging of various solid tumors. This advancement holds potential for early diagnosis of diverse CAIX-positive cancers.
Area of Science:
- Biomedical Engineering
- Oncology
- Diagnostic Imaging
Background:
- Ultrasound molecular imaging requires targeted contrast agents for tumor detection.
- Current agents are limited to blood pool or single tumor types, lacking broad applicability.
- Carbonic anhydrase IX (CAIX) is a promising target due to its high expression in various malignant solid tumors.
Purpose of the Study:
- To construct targeted nanobubbles carrying CAIX polypeptides for broad-spectrum tumor imaging.
- To evaluate the targeted binding ability and ultrasound imaging efficacy of these nanobubbles.
- To assess their potential for early diagnosis of diverse solid tumors.
Main Methods:
- Construction of lipid-based targeted nanobubbles functionalized with CAIX polypeptides.
- In vitro assessment of nanobubble binding affinity to CAIX-positive and CAIX-negative cells.
- In vivo evaluation of nanobubble accumulation and imaging signal in transplanted tumor models.
- Immunofluorescence to confirm nanobubble extravasation and tissue distribution.
Main Results:
- Targeted nanobubbles exhibited homogeneous particle size, high stability, and good safety.
- Significant in vitro accumulation of nanobubbles around CAIX-positive cells compared to CAIX-negative cells (P < 0.05).
- In vivo studies showed enhanced peak intensity and longer duration of ultrasound signals in CAIX-positive tumors compared to CAIX-negative tumors (P < 0.05).
- Immunofluorescence confirmed nanobubble entry into tumor tissue spaces and differential imaging in various tumor types.
Conclusions:
- Targeted nanobubbles carrying CAIX polypeptides demonstrate specific enhancement of ultrasound imaging in CAIX-positive tumor tissues.
- These nanobubbles show potential as a diagnostic tool for the early detection of various solid tumors.
- The developed agents offer a promising approach for molecular imaging across diverse CAIX-expressing malignancies.
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