Multivalent aptamer-modified tetrahedral DNA nanocage demonstrates high selectivity and safety for anti-tumor therapy

Abstract

Multivalent aptamer-modified tetrahedral DNA nanocage demonstrates high selectivity and safety for anti-tumor therapy in vivo.

Improving Breast Cancer Treatment Specificity Using Aptamers Obtained by 3D Cell-SELEX

“…Treatment with these polymers carrying payloads of doxorubicin results in breast cancer cell death only, while non-malignant breast cells largely survive. Compared to earlier studies [25][26][27][28][29][30][31][32][33][34][35]47,64,71,75,78,79,81,82], the response to selective treatment with doxorubicin is high, resulting in <5% cell survival of SKBR3 spheroid cells at a dose of 2 µM. Taken together, these results illustrate the high potential of our multimeric approach in breast cancer therapy.…”

“…The concept of multivalency, where multiple ligands bind simultaneously to multiple targets, in particular to receptors on a cell surface, has been used for enhancing binding affinity of aptamers in different contexts and designs [64][65][66][67]. Various types of constructs have been designed to achieve multivalency: Multimeric constructs, connected with nucleic acid, peptide, or artificial linkers [37,48,[68][69][70][71][72][73] of predefined length to tune the spacing in between aptamers, or nanoparticles [35,43,[74][75][76][77][78][79] or liposomes [62,64,[80][81][82] decorated with aptamers with pre-defined density. Polymeric designs as we report here have not been used widely in the construction and application of multimeric aptamers [37,[70][71][72][73].…”

“…Aptamers can be extended with short hairpins or double stranded DNA regions containing CpG stretches, which are known to efficiently intercalate Dox [21][22][23][24]. Instead of extending aptamers with DNA Dox carriers for targeted delivery, which has been the approach by various laboratories [25][26][27][28][29][30][31][32][33][34][35], here we use a modular approach, where we combine Dox carriers with high payload capacity with our selected aptamers using polymer synthesis, as schematized in Figure 5. Third, we assessed Dox toxicity by adding free Dox directly to SKBR3 and MCF10A spheroids at increasing Dox concentrations (Supplementary Figures S7 and S8).…”

<p>Nucleic Acid Aptamer: A Novel Potential Diagnostic and Therapeutic Tool for Leukemia</p>

“…Of note, the polyvalent aptamer system composed of multiple aptamer units and physically inserted chemotherapy agents, namely “Poly-Aptamer-Drug”, naturally presents enhanced binding affinity (～ 40 fold greater) and cellular internalization efficiency than monovalent counterpart in targeting and killing leukemia cells due to multivalent effects 99,100. For further monitoring anti-leukemia drug effect, the complex of localized surface plasmon resonance (LSPR) and gold nanorods (AuNR) functionalized with aptamers has been effectively used in preclinical stage through sensing the cytochrome-c released from apoptotic leukemia cells 101…”

Modelling the human heart: human stem cell-based models lead the way in physiological, pathological, and toxicological research

“…(60) As a consequence of this metabolic switch, mitochondrial respiration in the neonatal heart accounts for ~90% of the total ATP production, with a 10-fold increase in fatty acid oxidation, making it the dominant resource for oxidative phosphorylation. (60)(61)(62)(63) To accommodate this increased rate of β-oxidation, the mitochondria in neonatal CMs rapidly proliferate, relocate from perinuclear to peri-myofibrillar locations in the cell, and become more mature, leading to increased inner membrane surface area (the lamellar phenotype) and a 2-4 fold increase in expression of proteins involved in respiratory activity. The metabolic switch from a fetal to an adult phenotype coincides with a higher concentration of gene expression of key regulators in fatty acid transport and oxidation (60), such as peroxisome proliferator-activated receptor (PPAR)-α and γ. PPARs can exhibit their function only after establishing a transcriptional complex with their co-activators, such as PPARγ coactivator-1α (PGC-1α).…”