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Published on: February 2, 2013
Functional Tumor Targeting Nano-Systems for Reprogramming Circulating Tumor Cells with In Situ Evaluation on
Xiao-He Ren1, Xiao-Yan He2, Chang Xu1
1Key Laboratory of Biomedical Polymers of Ministry of Education, Department of Chemistry, Wuhan University, Wuhan, 430072, P. R. China.
Abstract:
Tumor heterogeneity is primarily responsible for treatment resistance and cancer relapses. Being critically important to address this issue, the timely evaluation of the appropriateness of therapeutic actions at the single-cell level is still facing challenges. By using multi-functionalized nano-systems with the delivery vector composed of histone for plasmids loading, hyaluronic acid for tumor targeting, and a fusion peptide for C-X-C motif chemokine receptor 4 (CXCR4） targeting as well as nuclear localization, the reprogramming of circulating tumor cells (CTCs) with in situ detection on biomarkers at the single-cell level is realized. By efficient co-delivery of the genome editing plasmid for CXCR4 knockout and molecular beacons for detection of upregulated mRNA biomarkers into CTCs in unprocessed whole blood, the therapeutic outcomes of genome editing at the single-cell level can be in situ evaluated. The single-cell analysis shows that CXCR4 in CTCs of cancer patients is efficiently downregulated, resulting in upregulated anticancer biomarkers such as p53 and p21. The study provides a facile strategy for in-depth profiling of cancer cell responses to therapeutic actions at single-cell resolution to evaluate the outcomes of treatments timely and conveniently.
Insights
This study developed a nano-system to reprogram circulating tumor cells (CTCs) and detect biomarkers. This allows for timely, single-cell evaluation of cancer treatment effectiveness, addressing resistance and relapse challenges.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Research
Background:
- Tumor heterogeneity drives treatment resistance and cancer recurrence.
- Evaluating therapeutic effectiveness at the single-cell level is crucial but challenging.
- Circulating tumor cells (CTCs) offer a window into treatment response.
Purpose of the Study:
- To develop a multi-functionalized nano-system for reprogramming CTCs.
- To enable in situ detection and evaluation of therapeutic outcomes at the single-cell level.
- To address challenges in timely assessment of cancer treatment appropriateness.
Main Methods:
- Utilized a nano-system with histone, hyaluronic acid, and a fusion peptide for plasmid and targeting delivery.
- Co-delivered a genome editing plasmid for C-X-C motif chemokine receptor 4 (CXCR4) knockout and molecular beacons for mRNA biomarker detection.
- Analyzed CTCs in unprocessed whole blood for reprogramming and biomarker expression.
Main Results:
- Successfully reprogrammed CTCs with efficient CXCR4 downregulation.
- Demonstrated in situ evaluation of genome editing outcomes at the single-cell level.
- Observed upregulation of anticancer biomarkers like p53 and p21 post-treatment.
Conclusions:
- The developed nano-system provides a facile strategy for single-cell analysis of cancer cell responses.
- Enables timely and convenient evaluation of therapeutic outcomes.
- Offers potential for improved cancer treatment monitoring and management.
