Aptamer-Functionalized Binary-Drug Delivery System for Synergetic Obesity Therapy

Abstract

The targeted delivery of phytochemicals that promote energy expenditure for obesity therapy remains a challenge. This study assembled a functionalized adipo-8 aptamer loaded with allicin using isothermal rolling-circle techniques to form a synergistic adipocyte-targeted binarydrug delivery system for treating obesity. The functionalized adipo-8 aptamer efficiently protected allicin from adsorption, showing significant potential to encapsulate, transport, and release molecular cargos into white adipose tissue. Introducing the negatively charged allicin, a phytochemical able to induce adipose tissue browning, reduced the diameters of DNAnanoflower from 770 to 380 nm and increased cellular uptake efficiency up to 118.7%. The intracellular distribution observed via confocal microscopy confirmed the successful receptor recognition mediated by aptamers in the DNA-nanoflower-allicin (NFA) framework as well as its excellent stability to escape from lysosomes. In vivo results demonstrated that subcutaneous administration of NFA effectively promoted adipocyte browning and systematic energy expenditure with minimal side effects. Furthermore, the G-quadruplex in the mitochondrial uncoupling protein-1 promoter was found to be an interactive allicin target for regulating thermogenesis to combat obesity.

One‐Pot Controllable Assembly of a Baicalin‐Condensed Aptamer Nanodrug for Synergistic Anti‐Obesity

“…Previous results suggested that G454 was the most stable quadruplex structure with three G‐tetrad layers in the UCP1 domain. [ 38 ] The nine docking models presented in Figure 3C indicated that baicalin interacted with the G454 quadruplex via conventional hydrogen, van der Waals forces, Pi–Pi interaction, and carbon hydrogens in the grooves of the G454‐folded structures (Figure S15 and Table S4, Supporting Information). The 3T3‐L1 preadipocytes were transfected by the G454‐containing UCP1 sequence‐inserted psiCHECK‐2 plasmid to facilitate Renilla and firefly luciferase expression (Figure 3D).…”

Smart Nucleic Acid Hydrogels with High Stimuli-Responsiveness in Biomedical Fields

“…The micromorphology of NAHs, such as the pore size and the degree of crosslink, have an essential effect on cell uptake. At present, NAHs prepared by RCA can be condensed by polyethyleneimine from a micrometer scale to nanoscale, which provide convenience for NAHs entering into the cell [94]. Using rational design for NAHs and exploring other size-controllable technologies will promote the development of NAHs in cell engineering.…”

Biomaterial-Based Therapeutic Strategies for Obesity and Its Comorbidities

“…After six weeks of administration to DIO mice, there were significant reductions in triglyceride, total cholesterol, and low-density lipoprotein (HDL) levels and substantial weight loss of approximately 12.8 ± 0.75%. To achieve adipocyte-targeted delivery of allicin, which is a phytochemical capable of inducing browning in adipose tissue, adipo-8 aptamer-modified DNA-nanoflower-allicin framework (NFA) was assembled using the isothermal rolling circle technique, which considerably enhanced the bioactivity and stability of allicin ( Figure 3 ) [ 125 ]. Mechanistic studies have shown that the target of allicin is the G-quadruplex (G4) in the mitochondrial uncoupling protein-1 (UCP1) promoter, and adipo-8 and allicin play a synergistic role in the activation of targeted thermogenic genes.…”