Issue 2 (July-Aug)
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Abstract: Ultrasound (US) has evolved from a predominantly diagnostic modality into a versatile therapeutic stimulus capable of controlling biological and material responses with considerable spatial and temporal precision. Ultrasound-activated biomaterials integrate acoustic energy with responsive carriers, hydrogels, nanoparticles, microbubbles, nanodroplets, and electroactive scaffolds to enable externally controlled drug release, gene delivery, barrier modulation, and tissue regeneration. The principal mechanisms include stable and inertial cavitation, acoustic streaming, radiation force, localized heating, sonoporation, mechanotransduction, and sonochemical generation of reactive oxygen species. These mechanisms can be exploited independently or in combination to generate pulsatile, delayed, sustained, or on-demand release profiles. Microbubbles and phase-change… Read more
Keywords: ultrasound-responsive biomaterials, spatiotemporal drug delivery, hydrogels, piezoelectric scaffolds, regenerative medicine, mechanotransduction
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Abstract: Plant-derived extracellular vesicles (PDEVs) have emerged as an attractive class of naturally occurring nanocarriers that combine the biological functionality of extracellular vesicles with the accessibility, scalability, and chemical diversity of plant sources. These nanoscale lipid-bilayer vesicles contain proteins, lipids, nucleic acids and plant-derived metabolites and can participate in intercellular and potentially cross-kingdom communication. Increasing evidence indicates that PDEVs can function not only as naturally bioactive nanoparticles but also as engineered delivery systems for small-molecule drugs, proteins and nucleic acids. Their membrane composition, intrinsic cellular uptake, gastrointestinal stability and possibility of oral or intranasal administration provide characteristics that are attractive… Read more
Keywords: Plant nanovesicles, drug delivery, precision nanomedicine, targeted delivery, nanopharmaceutics, RNA delivery
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Abstract: Protein structure is increasingly understood as a dynamic ensemble rather than a single rigid entity. Within this ensemble, transient cavities can emerge that are absent or poorly defined in conventional ligand-free structures. These cryptic binding pockets provide opportunities to modulate proteins for which conventional orthosteric drug discovery has been unsuccessful. Because many cryptic pockets are spatially separated from catalytic or orthosteric sites, their exploitation frequently overlaps with the pharmacological concept of allostery. Structural fluctuations, loop displacement, side-chain rearrangement, hydration changes, and domain motions can therefore generate previously unrecognized ligandable states. Experimental approaches including fragment-based crystallography, nuclear magnetic resonance, hydrogen–deuterium… Read more
Keywords: Cryptic Pocket, Allostery, Protein Dynamics, KRAS, Mutant p53, BACE-1
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Abstract: RNA is emerging as a chemically tractable therapeutic target rather than merely an intermediary between DNA and proteins. Its diverse secondary, tertiary, and quaternary structures create ligandable environments for small molecules, although dynamic conformations, electrostatic surfaces, and recurrent motifs complicate selective targeting. Cryptic RNA pockets are particularly promising sites that are weakly populated or inaccessible in the unbound state but become exposed or reorganized upon ligand binding. Riboswitches provide natural models for this mechanism, while recent studies have extended RNA targeting to hairpins, internal loops, bulges, G-quadruplexes, viral regulatory elements, precursor microRNAs, long non-coding RNAs, and RNA–protein interfaces. Advances… Read more
Keywords: RNA targeting, small molecules, cryptic pockets, riboswitch, RIBOTAC, Inforna