Targeted-Lymphoma Drug Delivery System Based on the Sgc8-c Aptamer.
Estefanía SiccoHugo E CerecettoVictoria CalzadaMaría MorenoPublished in: Cancers (2023)
Aptamers are emerging as a promising new class of functional nucleic acids because they can specifically bind to any target with high affinity and be easily modified chemically with different pharmacophoric subunits for therapy. The truncated aptamer, Sgc8-c, binds to tyrosine-protein kinase-like 7 receptor, a promising cancer therapeutic target, allowing the recognition of haemato-oncological malignancies, among others. We have previously developed aptamer-drug conjugates by chemical synthesis, hybridizing Sgc8-c and dasatinib, a drug proposed for lymphoma chemotherapy. One of the best-characterised Sgc8-c-dasatinib hybrids, namely Sgc8-c-carb-da , was capable of releasing dasatinib at an endosomal-pH. Herein, we probed the therapeutic potential of this aptamer-drug conjugate. Sgc8-c-carb-da specifically inhibited murine A20 B lymphocyte growth and produced cell death, mainly by late apoptosis and necrosis. In addition, Sgc8-c-carb-da generated an arrest in cell proliferation, with a cell cycle arrest in the Sub-G1-peak. The mitochondrial potential was altered accordingly to these pathways. Moreover, using an in vitro cell-targeting assay that mimics in vivo conditions, we showed that Sgc8-c-carb-da displayed higher (2.5-fold) cytotoxic effects than dasatinib. These findings provide proof-of-concept of the therapeutic value of Sgc8-c-carb-da for lymphoma, creating new opportunities for the chemical synthesis of targeted biotherapeutics.
Keyphrases
- cell death
- cell cycle arrest
- gold nanoparticles
- cancer therapy
- cell proliferation
- diffuse large b cell lymphoma
- sensitive detection
- oxidative stress
- pi k akt
- magnetic nanoparticles
- prostate cancer
- emergency department
- signaling pathway
- single cell
- young adults
- drug induced
- climate change
- adverse drug
- electronic health record
- squamous cell
- anti inflammatory