Aptamer-based liposomes improve specific drug loading and release

Abstract

Aptamer technology has shown much promise in cancer therapeutics for its targeting abilities. However, its potential to improve drug loading and release from nanocarriers has not been thoroughly explored. In this study, we employed drug-binding aptamers to actively load drugs into liposomes. We designed a series of DNA aptamer sequences specific to doxorubicin, displaying multiple binding sites and various binding affinities. The binding ability of aptamers was preserved when incorporated into cationic liposomes, binding up to 15equivalents of doxorubicin per aptamer, therefore drawing the drug into liposomes. Optimization of the charge and drug/aptamer ratios resulted in ≥80% encapsulation efficiency of doxorubicin, ten times higher than classical passively-encapsulating liposomal formulations and similar to a pH-gradient active loading strategy. In addition, kinetic release profiles and cytotoxicity assay on HeLa cells demonstrated that the release and therapeutic efficacy of liposomal doxorubicin could be controlled by the aptamer's structure. Our results suggest that the aptamer exhibiting a specific intermediate affinity is the best suited to achieve high drug loading while maintaining efficient drug release and therapeutic activity. This strategy was successfully applied to tobramycin, a hydrophilic drug suffering from low encapsulation into liposomes, where its loading was improved six-fold using aptamers. Overall, we demonstrate that aptamers could act, in addition to their targeting properties, as multifunctional excipients for liposomal formulations.

Aptamer Grafting onto (on) and into (in) Pegylated Gold Nanoparticles: Physicochemical Characterization and In vitro Cytotoxicity Investigation in Renal Cells

“…However, its potential to improve drug loading and release from nano carriers has not been thoroughly analyzed. Recently Lee JB et al have proposed a general approach for loading a large amount of thrombin proteins using DNA aptamer particles [52]; other authors, have developed a new strategy of drug-loading by designing drug specific aptamers to drive drugs into liposomes [53]. Of note, Dam et al [54] showed thatloading of G-quadruplex DNA aptamer AS1411 onto AuNPs could be tuned by manipulating the charge of the ligands and the particle surface by pH.…”

Programmable and Multifunctional DNA‐Based Materials for Biomedical Applications

“…Aptamers' targeting abilities have been widely exploited, but its potential to improve drug loading and release from nanocarriers was thoroughly unexplored. Plourde et al hence utilized drug‐binding aptamers to load DOX into cationic liposomes and optimization of the charge and drug/aptamer ratios resulted in ≥80% encapsulation efficiency, tenfold improvement than classical passively encapsulating liposomal formulations …”

Applications of Aptamers in Drug Delivery System

“…The past few years has witnessed the great advances in the synthesis and characterization of various nanomaterials, such as dots, [17,18] gold nanomaterials, [19] hydrogel [20] carbon nanotubes [21] liposome [22] and so on. The combination of aptamers with novel nanomaterials has led to a wide applications.…”