Assessment of Aptamer as a Potential Drug Targeted Delivery for Retinal Angiogenesis Inhibition

Abstract

AT11-L0 is an aptamer derivative of AS1411 composed of G-rich sequences that can adopt a G-quadruplex (G4) structure and target nucleolin (NCL), a protein that acts as a co-receptor for several growth factors. Hence, this study aimed to characterize the AT11-L0 G4 structure and its interaction with several ligands for NCL targeting and to evaluate their capacity to inhibit angiogenesis using an in vitro model. The AT11-L0 aptamer was then used to functionalize drug-associated liposomes to increase the bioavailability of the aptamer-based drug in the formulation. Biophysical studies, such as nuclear magnetic resonance, circular dichroism, and fluorescence titrations, were performed to characterize the liposomes functionalized with the AT11-L0 aptamer. Finally, these liposome formulations with the encapsulated drugs were tested on the human umbilical vein endothelial cell (HUVEC) model to assess their antiangiogenic capacity. The results showed that the AT11-L0 aptamer–ligand complexes are highly stable, presenting melting temperatures from 45 °C to 60 °C, allowing for efficient targeting of NCL with a KD in the order of nM. The aptamer-functionalized liposomes loaded with ligands C8 and dexamethasone did not show cytotoxic effects in HUVEC cells compared with the free ligands and AT11-L0, as assessed by cell viability assays. AT11-L0 aptamer-functionalized liposomes encapsulating C8 and dexamethasone did not present a significant reduction in the angiogenic process when compared with the free ligands. In addition, AT11-L0 did not show anti-angiogenic effects at the concentrations tested. However, C8 shows potential as an angiogenesis inhibitor, which should be further developed and optimized in future experiments.

Advancements in Nanogels for Enhanced Ocular Drug Delivery: Cutting-Edge Strategies to Overcome Eye Barriers

“…Moreover, an in vivo study with a rat dry eye disease (DED) model was conducted to demonstrate the efficacy of aptamer-functionalized liposomes in restoring tear production and corneal integrity. Furthermore, other investigations on aptamer derivatives for the inhibition of retinal angiogenesis have also been undertaken by Moreira et al [ 150 ]. However, research on whether aptamer derivatives can actually reach the retina through in vivo experiments is yet to be conducted, indicating that additional experiments are likely needed.…”

Aptamers’ Potential to Fill Therapeutic and Diagnostic Gaps

“…This is the case for AT11-L0, a DNA aptamer targeted against the nucleolin (NCL), a nuclear protein that plays an important role in angiogenesis in retinal neovascular diseases, since its inhibition promotes an antiangiogenic effect [ 87 ]. This aptamer has been used by Moreira and co-workers to functionalize liposomes that could be loaded with antiangiogenetic drugs [ 88 ]. The authors show that the complexes allow efficient targeting of NCL, making liposomes functionalized with this aptamer a promising tool to enable effective anti-angiogenic drug delivery.…”