Aptamer-functionalized liposome delivery system targeting adipose for hypereffective obesity therapy

Preparation of DNA micro/nanostructures with high accuracy, high effectiveness, and low toxicity remains a challenge in the fields of biotargeting drugs and therapeutics. Aptamer-liposome-nordihydrocapsaicin-encapsulated nanosystems (ALN) were constructed via film dispersion ultrasonication using liposome-anchored aptamers for synergistic obesity treatment. In this design, 71 nucleotide (nt) long of adipo-8, which had good anti-obesity targeting activity, was loaded into liposomes via lipophilic interactions, and nordihydrocapsaicin (NOR) and the aptamer precisely targeted mature adipocytes, lipid-lowering factors, and thermogenic activators. The functionalized liposome adipo-8 aptamer effectively protected NOR from adsorption and showed significant potential for the encapsulation, transport, and release of molecular cargo in white adipose tissue. ALN was a multifunctional composite nanomaterial, with a particle size of approximately 106.07 nm. The cellular uptake of the ALN (up to 87.07%) was considerably improved compared with that of the unencapsulated material. In vivo targeting showed that ALN reached the target site and remained in organs and adipose tissue for up to 48 h with a good sustained-release quantity. The ALN-targeted delivery resulted in up to 3.636% drug content in adipose tissue and a 53.3% reduction in the body weight of mice. ALN exerted a synergistic effect in the treatment of obesity in vitro and in vivo, thus providing a new direction for the targeted delivery of nanomedicines. Moreover, in vivo experimental results showed that the subcutaneous injection of ALN effectively promoted adipose tissue lipolysis and energy expenditure with minimal side effects.