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Targeted-Lymphoma Drug Delivery System Based on the Sgc8-c Aptamer
Estefanía Sicco1,2, Hugo Cerecetto1, Victoria Calzada1
1Área de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Montevideo 11400, Uruguay.
Cancers
|February 11, 2023
Summary
This study shows Sgc8-c-carb-da, an aptamer-drug conjugate, effectively inhibits lymphoma B lymphocyte growth and induces cell death. It demonstrates superior cytotoxic effects compared to dasatinib alone, offering potential for targeted lymphoma therapies.
Area of Science:
- Biochemistry
- Molecular Biology
- Cancer Therapeutics
Background:
- Aptamers are functional nucleic acids with high specificity and affinity for targets.
- Tyrosine-protein kinase-like 7 receptor is a target for hematologic malignancies.
- Aptamer-drug conjugates offer targeted delivery of therapeutics.
Purpose of the Study:
- To evaluate the therapeutic potential of the aptamer-drug conjugate Sgc8-c-carb-da.
- To assess the efficacy of Sgc8-c-carb-da against murine A20 B lymphocyte growth.
- To compare the cytotoxic effects of Sgc8-c-carb-da with dasatinib.
Main Methods:
- Chemical synthesis of Sgc8-c-carb-da conjugate.
- In vitro assays to assess cell growth inhibition and cell death.
- Cell cycle analysis and mitochondrial potential measurements.
- In vitro cell-targeting assay mimicking in vivo conditions.
Main Results:
- Sgc8-c-carb-da specifically inhibited murine A20 B lymphocyte growth.
- The conjugate induced cell death via late apoptosis and necrosis.
- Sgc8-c-carb-da caused cell cycle arrest in the Sub-G1 phase and altered mitochondrial potential.
- Sgc8-c-carb-da exhibited 2.5-fold higher cytotoxicity than dasatinib in vitro.
Conclusions:
- Sgc8-c-carb-da demonstrates significant therapeutic potential for lymphoma treatment.
- The aptamer-drug conjugate offers a targeted approach to cancer biotherapeutics.
- These findings support the development of novel chemically synthesized targeted biotherapeutics.
