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Homotypic-Targeted Mineralized Tumor Cell Probes for Ultrasensitive MRI Diagnosis of Early-Stage Malignancies
Peiru Lin1, Wanjia Wu2, Yuanyuan You1
1NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, 510515 Guangzhou, China.
Abstract:
The effectiveness of clinically used magnetic resonance imaging (MRI) contrast agents (CAs) in tumor diagnosis is limited due to their low selectivity and sensitivity. To address this, we propose inactivated cell-based contrast agents (Mn-CCs) by constructing a mineralized tumor cell. Preserving proteins and structures on the cell membrane, Mn-CCs exhibit advantages, including homotypic targeting capabilities, tumor microenvironment (TME)-activated MRI signals, and ultrahigh relaxation rates. Glioma and pancreatic tumor cells were used as model templates to produce Mn-UCs and Mn-SCs. Under TME conditions, the longitudinal relaxation rates of Mn-UCs and Mn-SCs increased to 13.27 and 5.48 mM-1s-1, respectively. In vivo results demonstrated that Mn-UCs showed a superior MRI contrast enhancement in glioma compared to clinically used Gd-DOTA. Furthermore, Mn-SCs specifically enhanced MRI contrast in pancreatic tumors as small as 5.67 ± 1.16 mm3 and enabled clear differentiation between tumor stages. The biosafety, sensitivity, and specificity of Mn-CCs suggest a novel approach for designing biomimetic MRI contrast agents, offering new opportunities for more precise diagnosis of early-stage tumors.
Insights
Researchers developed novel inactivated cell-based contrast agents (Mn-CCs) for enhanced tumor diagnosis. These biomimetic agents improve magnetic resonance imaging (MRI) sensitivity and specificity, enabling earlier and more accurate detection of various cancers.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Medical Imaging
Background:
- Clinically used MRI contrast agents (CAs) have limited selectivity and sensitivity for tumor diagnosis.
- There is a need for advanced contrast agents with improved targeting and signal amplification.
Purpose of the Study:
- To develop novel inactivated cell-based contrast agents (Mn-CCs) for enhanced MRI tumor detection.
- To evaluate the performance of Mn-CCs in terms of targeting, signal activation, and diagnostic accuracy.
Main Methods:
- Constructed mineralized tumor cells (Mn-CCs) using glioma and pancreatic tumor cell templates.
- Assessed Mn-CCs' MRI signal properties under tumor microenvironment (TME) conditions.
- Evaluated in vivo MRI contrast enhancement and tumor detection capabilities in preclinical models.
Main Results:
- Mn-CCs demonstrated homotypic targeting and TME-activated MRI signals.
- Achieved significantly increased longitudinal relaxation rates under TME conditions.
- Mn-CCs showed superior MRI contrast enhancement in glioma and specific detection of small pancreatic tumors, outperforming Gd-DOTA.
Conclusions:
- Mn-CCs represent a promising biomimetic approach for developing sensitive and specific MRI contrast agents.
- These agents offer potential for improved early-stage tumor diagnosis and differentiation.
- The study highlights a novel strategy for designing advanced contrast agents with enhanced biosafety and efficacy.
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