Multivalent rubber-like RNA nanoparticles for targeted co-delivery of paclitaxel and MiRNA to silence the drug efflux transporter and liver cancer drug resistance.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Analogous to the border customs, liver mainly functions as a filter to detoxify chemicals and metabolite administered orally or intravenously. Besides, the liver cancer cells overexpress the drug exporters which cause high drug effluxion from liver cancer cells, leading to chemoresistance and a diminished chemotherapeutic effect on liver cancer.

RNA Nanoparticles as Rubber for Compelling Vessel Extravasation to Enhance Tumor Targeting and for Fast Renal Excretion to Reduce Toxicity.

Rubber is a fascinating material in both industry and daily life. The development of elastomeric material in nanotechnology is imperative due to its economic and technological potential. By virtue of their distinctive physicochemical properties, nucleic acids have been extensively explored in material science.

Self-assembly of four generations of RNA dendrimers for drug shielding with controllable layer-by-layer release.

Chemical dendrimers have been shown to be a promising drug delivery platform due to their advantageous properties such as monodispersity, multivalency and branched structure. Taking advantage of self-assembly and its intrinsic negative charge, we used RNA as the building block for dendrimer construction to eliminate complex synthesis procedures and cationic charge-related toxicity. Oligo ribonucleotides produced by solid phase chemical synthesis allow the large-scale manufacture of homologous RNA dendrimers.

Ultra-thermostable RNA nanoparticles for solubilizing and high-yield loading of paclitaxel for breast cancer therapy.

Paclitaxel is widely used in cancer treatments, but poor water-solubility and toxicity raise serious concerns. Here we report an RNA four-way junction nanoparticle with ultra-thermodynamic stability to solubilize and load paclitaxel for targeted cancer therapy. Each RNA nanoparticle covalently loads twenty-four paclitaxel molecules as a prodrug.

Synergistic SHAPE/Single-Molecule Deconvolution of RNA Conformation under Physiological Conditions.

Structural RNA domains are widely involved in the regulation of biological functions, such as gene expression, gene modification, and gene repair. Activity of these dynamic regions depends sensitively on the global fold of the RNA, in particular, on the binding affinity of individual conformations to effector molecules in solution. Consequently, both the 1) structure and 2) conformational dynamics of noncoding RNAs prove to be essential in understanding the coupling that results in biological function.

RNA-based micelles: A novel platform for paclitaxel loading and delivery.

RNA can serve as powerful building blocks for bottom-up fabrication of nanostructures for biotechnological and biomedical applications. In addition to current self-assembly strategies utilizing base pairing, motif piling and tertiary interactions, we reported for the first time the formation of RNA based micellar nanoconstruct with a cholesterol molecule conjugated onto one helical end of a branched pRNA three-way junction (3WJ) motif. The resulting amphiphilic RNA micelles consist of a hydrophilic RNA head and a covalently linked hydrophobic lipid tail that can spontaneously assemble in aqueous solution via hydrophobic interaction.

Mechanism of three-component collision to produce ultrastable pRNA three-way junction of Phi29 DNA-packaging motor by kinetic assessment.

RNA nanotechnology is rapidly emerging. Due to advantageous pharmacokinetics and favorable in vivo biodistribution, RNA nanoparticles have shown promise in targeted delivery of therapeutics. RNA nanotechnology applies bottom-up assembly, thus elucidation of the mechanism of interaction between multiple components is of fundamental importance.

Single-Molecule FRET Reveals Three Conformations for the TLS Domain of Brome Mosaic Virus Genome.

Metabolite-dependent conformational switching in RNA riboswitches is now widely accepted as a critical regulatory mechanism for gene expression in bacterial systems. More recently, similar gene regulation mechanisms have been found to be important for viral systems as well. One of the most abundant and best-studied systems is the tRNA-like structure (TLS) domain, which has been found to occur in many plant viruses spread across numerous genera.

Discovery of a new method for potent drug development using power function of stoichiometry of homomeric biocomplexes or biological nanomotors.

Introduction: Multidrug resistance and the appearance of incurable diseases inspire the quest for potent therapeutics.

Areas Covered: We review a new methodology in designing potent drugs by targeting multi-subunit homomeric biological motors, machines or complexes with Z > 1 and K = 1, where Z is the stoichiometry of the target, and K is the number of drugged subunits required to block the function of the complex. The condition is similar to a series electrical circuit of Christmas decorations: failure of one light bulb causes the entire lighting system to lose power.

Functional assays for specific targeting and delivery of RNA nanoparticles to brain tumor.

Cumulative progress in nanoparticle development has opened a new era of targeted delivery of therapeutics to cancer cells and tissue. However, developing proper detection methods has lagged behind resulting in the lack of precise evaluation and monitoring of the systemically administered nanoparticles. RNA nanoparticles derived from the bacteriophage phi29 DNA packaging motor pRNA have emerged as a new generation of drugs for cancer therapy.

Using RNA nanoparticles with thermostable motifs and fluorogenic modules for real-time detection of RNA folding and turnover in prokaryotic and eukaryotic cells.

RNA nanotechnology is an emerging field at the interface of biochemistry and nanomaterials that shows immense promise for applications in nanomedicines, therapeutics and nanotechnology. Noncoding RNAs, such as siRNA, miRNA, ribozymes, and riboswitches, play important roles in the regulation of cellular processes. They carry out highly specific functions on a compact and efficient footprint.

Two classes of nucleic acid translocation motors: rotation and revolution without rotation.

Biomotors are extensively involved in biological processes including cell mitosis, bacterial binary fission, DNA replication, DNA repair, homologous recombination, Holliday junction resolution, RNA transcription, and viral genome packaging. Traditionally, they were classified into two categories including linear and rotation motors. In 2013, a third class of motor by revolution mechanism without rotation was discovered.

Conformationally dynamic π-conjugation: probing structure-property relationships of fluorescent tris(N-salicylideneaniline)s.

We recently reported the design and synthesis of a series of conformationally dynamic chromophores that are built on the C(3)-symmetric tris(N-salicylideneaniline) platform. This system utilizes cooperative structural folding-unfolding motions for fluorescence switching, which is driven by the assembly and disassembly of hydrogen bonds between the rigid core and rotatable peripheral part of the molecule. Here, we report detailed time-resolved spectroscopic studies to investigate the structure-property relationships of a series of functionalized tris(N-salicylideneaniline)s.

Photothermal imaging and measurement of protein shell stoichiometry of single HIV-1 Gag virus-like nanoparticles.

Virus life stages often constitute a complex chain of events, difficult to track in vivo and in real-time. Challenges are associated with spatial and time limitations of current probes: most viruses are smaller than the diffraction limit of optical microscopes while the entire time scale of virus dynamics spans over 8 orders of magnitude. Thus, virus processes such as entry, disassembly, and egress have generally remained poorly understood.

Reactivity-based fluoride detection: evolving design principles for spring-loaded turn-on fluorescent probes.

A covalently triggered fluorescence turn-on detection scheme has been implemented for a tris(N-salicylideneamine)-derived dynamic fluorophore. Selective cleavage of strategically placed Si-O bonds by fluoride ion induces spring-loaded conformational transitions that are tightly coupled to fluorescence enhancement.