Release Of Molecular Cargo Research Articles

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.

Frontispiece: Release of Molecular Cargo from Polymer Systems by Mechanochemistry

The incorporation of force-responsive groups, known as mechanophores, into macromolecular nanosystems has enabled access to previously unseen responsive behaviours as well as sophisticated functions of the resulting structures and advanced materials. The on-demand release or activation of compounds such as reaction catalysts, pharmaceutically active compounds, or monomers for self-healing of a material by an external trigger is a desired and important goal. In this review, we show how sonochemical activation by ultrasound (ultrasound-induced mechanochemistry) and the compression of bulk material can be used to create molecular cargo release systems from polymer-based architectures in solution. We also discuss important design concepts for these truly advanced materials, as well as their synthesis and applications. More information can be found in the Review article by B. M. Schmidt et al. (DOI: 10.1002/chem.202103860).

Release of Molecular Cargo from Polymer Systems by Mechanochemistry.

The design and manipulation of (multi)functional materials at the nanoscale holds the promise of fuelling tomorrow's major technological advances. In the realm of macromolecular nanosystems, the incorporation of force‐responsive groups, so called mechanophores, has resulted in unprecedented access to responsive behaviours and enabled sophisticated functions of the resulting structures and advanced materials. Among the diverse force‐activated motifs, the on‐demand release or activation of compounds, such as catalysts, drugs, or monomers for self‐healing, are sought‐after since they enable triggering pristine small molecule function from macromolecular frameworks. Here, we highlight examples of molecular cargo release systems from polymer‐based architectures in solution by means of sonochemical activation by ultrasound (ultrasound‐induced mechanochemistry). Important design concepts of these advanced materials are discussed, as well as their syntheses and applications.

Molecular cargo delivery using multicellular magnetic microswimmers

The recent emergence of versatile micro/nanorobots provides new strategies of healthcare and disease treatment, especially for targeted delivery of therapeutic agents to otherwise inaccessible regions. However, for successful translation of laboratory microrobotic tools into clinical outcomes, critical challenges still remain, such as controllable cargo loading/release on site, robust spatiotemporal navigation in real time and reliable biocompatibility/biodegradation inside the body. Herein, we report the loading, transport and release of molecular cargos using cell-based magnetic microswimmers engineered from multicellular Spirulina. The loading is attained by harnessing the dehydration and rehydration of Spirulina cells, inside which model macromolecules are encapsulated as a discrete phase, and for small molecules, as a continuous phase. Driven by low-strength magnetic fields, the molecule-laden swimmer manages to perform navigation in an intestinal tract mimicry, imitating the process of guest-molecule transport in the gastrointestinal tract. The loaded molecules can be released from the swimmer through host degradation and/or concentration gradient-driven diffusion, with the speed of release tailored by the magnetite-coating thickness. Furthermore, evaluation tests in a stem-cell system infer that the bioactivity of the guest molecules remains intact after the loading-release procedure. In summary, we have demonstrated a feasible approach for gastrointestinal delivery of molecular agents using cell-based microswimmers.

Dissipative Synthetic DNA‐Based Receptors for the Transient Loading and Release of Molecular Cargo

AbstractSupramolecular chemistry is moving into a direction in which the composition of a chemical equilibrium is no longer determined by thermodynamics but by the efficiency with which kinetic states can be populated by energy consuming processes. Herein, we show that DNA is ideally suited for programming chemically fueled dissipative self‐assembly processes. Advantages of the DNA‐based systems presented in this study include a perfect control over the activation site for the chemical fuel in terms of selectivity and affinity, highly selective fuel consumption that occurs exclusively in the activated complex, and a high tolerance for the presence of waste products. Finally, it is shown that chemical fuels can be used to selectively activate different functions in a system of higher complexity embedded with multiple response pathways.

Dissipative Synthetic DNA-Based Receptors for the Transient Loading and Release of Molecular Cargo.

Supramolecular chemistry is moving into a direction in which the composition of a chemical equilibrium is no longer determined by thermodynamics but by the efficiency with which kinetic states can be populated by energy consuming processes. Herein, we show that DNA is ideally suited for programming chemically fueled dissipative self-assembly processes. Advantages of the DNA-based systems presented in this study include a perfect control over the activation site for the chemical fuel in terms of selectivity and affinity, highly selective fuel consumption that occurs exclusively in the activated complex, and a high tolerance for the presence of waste products. Finally, it is shown that chemical fuels can be used to selectively activate different functions in a system of higher complexity embedded with multiple response pathways.

The unique self-assembly/disassembly property of Archaeoglobus fulgidus ferritin and its implications on molecular release from the protein cage

BackgroundIn conventional in vitro encapsulation of molecular cargo, the multi-subunit ferritin protein cages are disassembled in extremely acidic pH and re-assembled in the presence of highly concentrated cargo materials, which results in poor yields due to the low-pH treatment. In contrast, Archaeoglobus fulgidus open-pore ferritin (AfFtn) and its closed-pore mutant (AfFtn-AA) are present as dimeric species in neutral buffers that self-assemble into cage-like structure upon addition of metal ions. MethodsTo understand the iron-mediated self-assembly and ascorbate-mediated disassembly properties, we studied the iron binding and release profile of the AfFtn and AfFtn-AA, and the corresponding oligomerization of their subunits. ResultsFe2+ binding and conversion to Fe3+ triggered the self-assembly of cage-like structures from dimeric species of AfFtn and AfFtn-AA subunits, while disassembly was induced by dissolving the iron core with reducing agents. The closed-pore AfFtn-AA has identical iron binding kinetics but lower iron release rates when compared to AfFtn. While the iron binding rate is proportional to Fe2+ concentration, the iron release rate can be controlled by varying ascorbate concentrations. ConclusionThe AfFtn and AfFtn-AA cages formed by iron mineralization could be disassembled by dissolving the iron core. The open-pores of AfFtn contribute to enhanced reductive iron release while the small channels located at the 3-fold symmetry axis (3-fold channels) are used for iron uptake. General significanceThe iron-mediated self-assembly/disassembly property of AfFtn offers a new set of molecular trigger for formation and dissociation of the protein cage, which can potentially regulate uptake and release of molecular cargo from protein cages.

Encapsulation and Release of Molecular Cargos via Temperature‐Induced Vesicle‐To‐Micelle Transitions

Temperature-induced vesicle-to-micelle transitions of polystyrene-block-poly acrylic acid (PS(139)-b-PAA(17)) aggregates in tetrahydrofuran (THF)/H(2)O solvent mixtures are studied. For a typical system with an initial concentration of PS(139)-b-PAA(17) of 2 wt% and 50 vol% of H(2)O, the morphology of the aggregates changes from vesicles to micelles upon heating from room temperature to 45 °C. The transition temperature is found to depend on the polymer concentration as well as solvent composition. A higher polymer concentration results in a higher transition temperature. The morphological change is attributed to a change in the solvent-polymer interactions, which results in a reduction in interfacial energy. The corresponding temperature-induced morphological change is employed as a strategy for the reversible release and encapsulation of small molecules. The release of Rhodamine 110 bisamide above the transition temperature is observed as a result of the trypsin-catalyzed hydrolysis of the bisamide into Rhodamine 110. Likewise, the successful encapsulation of Rhodamine 110 below the transition temperature is proven using sodium nitrite as a chemical quencher.