Effect of Micelle Composition on Acidic Drugs Separation Behavior by Micellar Electrokinetic Capillary Chromatography

Micellar electrokinetic capillary chromatography (MECC) separation of four acidic drugs similar in structure was studied. Both anionic surfactant sodium dodecyl sulfate (SDS) and nonionic surfactant Tween 20 were used to form single micelles and mixed micelles as pseudostationary phases. The effects of the composition of micellar solution on retention behaviors were studied. The results indicate that there is markedly different selectivity among SDS, Tween 20 and the mixed micelles systems.

Synergistic Effects of 18β-glycyrrhetinic Acid Combined with Antituberculosis Drugs against Mycobacterium tuberculosis

The in vitro antibacterial activities of 18β-glycyrrhetinic acid alone or combined with first-line antituberculosis drugs including isoniazid（INH）,rifampicin（RFP） and streptomycin（SM） against Mycobacterium tuberculosis were detected using MABA method.The minimum inhibitory concentrations（MICs） of18β-glycyrrhetinic acid against M.tuberculosis H37Rv（ATCC 27294） and M.bovis（ATCC 19210） were 50 and 100 μg/m L,respectively.The MICs of two clinical drug-susceptible isolates and six drug-resistant isolates were 25-50 and 100-200 μg/m L,respectively.As 18β-glycyrrhetinic acid combined with INH,RFP and SM,they exhibited synergistic effects against six drug-resistant isolates,and MICs decreased significantly：MIC of INH decreased by 2-32 folds（FICIs 0.125-0.375）;MIC of RFP decreased by 4-8 folds（FICIs 0.240-0.490）;MIC of SM decreased by 4-16 folds（FICIs 0.165-0.460）.Traditional medicine monomer had low cytotoxicity on normal cell BHK-21 and could restraint SMMC fission.The results showed that 18β-glycyrrhetinic acid combined with anti-TB drugs（INH,RFP and SM） had good antibacterial activity against M.tuberculosis.These findings indicated that 18β-glycyrrhetinic acid might serve as the potential therapeutic compound for future development of anti-TB drugs.

Recent progress of aptamer-drug conjugates in cancer therapy

Aptamers are single-stranded DNA or RNA sequences that can specifically bind with the target protein or molecule via specific secondary structures.Compared to antibody-drug conjugates(ADC),aptamer-drug conjugate(ApDC)is also an efficient,targeted drug for cancer therapy with a smaller size,higher chemical stability,lower immunogenicity,faster tissue penetration,and facile engineering.Despite all these advantages,several key factors have delayed the clinical translation of ApDC,such as in vivo off-target effects and potential safety issues.In this review,we highlight the most recent progress in the development of ApDC and discuss solutions to the problems noted above.

Design of nanocarriers for efficient cellular uptake and endosomal release of small molecule and nucleic acid drugs： learning from virus

There are many challenges in developing efficient and target specific delivery systems of small molecule and nucleic acid drugs. Cell membrane presents one of the major barriers for the penetration of hydrophilic macromolecules across the plasma membrane. Nanocar- riers have been designed to enhance their cellular uptake via endocytosis but following their cellular uptake, endosomal escape is the rate limiting step which restricts the value associated with the enhanced uptake by nanocarriers. Viruses are an excellent model for efficient cytosolic delivery by nanocarriers. Viruses exploit intra- cellular cues to release the genome to cytosol. In this review, we first discuss different endocytic uptake path- ways and endosomal escape mechanisms. We then summarize the existing tools for studying the intracellular trafficking of nanocarriers. Finally, we highlight the important design elements of recent virus-based nanocar- tiers for efficient cellular uptake and endosomal escape.

Cadmium nanoclusters in a protein matrix： Synthesis, characterization, and application in targeted drug delivery and cellular imaging

Biotemplated metal nanoclusters have garnered much attention owing to their wide range of potential applications in biosensing, bioimaging, catalysis, and nanomedicine. Here, we report the synthesis of stable, biocompatible, watersoluble, and highly fluorescent bovine serum albumin-templated cadmium nanoclusters （CdNcs） through a facile one-pot green method. We covalently conjugated hyaluronic acid （HA） to the CdNcs to form a pH-responsive, tumor- targeting theranostic nanocarrier with a sustained release profile for doxorubicin （DOX）, a model anticancer drug. The nanocarrier showed a DOX encapsulation efficiency of about 75.6%. DOX release profiles revealed that 74% of DOX was released at pH 5.3, while less than 26% of DOX was released at pH 7.4 within the same 24-h period. The nanocarrier selectively recognized MCF-7 breast cancer cells expressing CD44, a cell surface receptor for HA, whereas no such recognition was observed with HA receptor-negative HEK293 cells. Biocompatibility of the nanocarrier was evaluated through cytotoxicity assays with HEK293 and MCF-7 ceils. The nanocarrier exhibited very low to no cytotoxicity, whereas the DOX-loaded nanocarrier showed considerable cellular uptake and enhanced MCF-7 breast cancer cell-killing ability. We also confirmed the feasibility of using the highly fluorescent nanoconjugate for bioimaging of MCF-7 and HeLa cells. The superior targeted drug delivery efficacy, cellular imaging capability, and low cytotoxicity position this nanoconjugate as an exciting new nanoplatform with promising biomedical applications.

The Preparation of Cationic Folic Acid and Its Application in Drug Delivery System

The cationic folic acid（CFA） was prepared by introducing triethylenetetramine into folic acid with EDCI/NHS and characterized by IR, NMR and mass spectra. It was found that approximately one of two carboxyls in the folic acid molecule was substituted to form CFA. The conversion of γ-carboxyl is found to be 59% higher than 30% of γ-carboxyl. The CFA and doxorubicin hydrochloride can be loaded on the ionic shell of PTX-encapsulated micelle to form CFA loaded binary drug carrier via static interaction in aqueous solutions. The successful loading was demonstrated by zeta potential measurement and the drug load amount（DLA） of CFA was measured by HPLC. In vitro cytotoxicity results revealed the CFA drug carrier showed higher cytotoxicity to cancer cell MDA-MB-321 than the binary drug carrier without CFA and the positive control, while it showed lower cytotoxicity to normal cell HUVEC than the positive control, and similar cytotoxicity with the binary drug carrier without CFA. These results as well as confocal laser scanning microscopy observation indicate the synthesized CFA drug carrier possesses active tumor-targeting property.

Novel liver-specific nitric oxide(NO) releasing drugs with bile acid as both NO carrier and targeting ligand

Novel liver-specific nitric oxide（NO） releasing drugs with bile acid as both the NO carrier and targeting ligand were designed and synthesized by direct nitration of the hydroxyl group in bile acids or the 3-Ohydroxyl alkyl derivatives,with the intact 24-COOH being preserved for hepatocyte specific recognition.Preliminary biological evaluation revealed that oral administrated targeted conjugates could protect mice against acute liver damage induced by acetaminophen or carbon tetrachloride.The nitrate level in the liver significantly increased after oral administration of 1e while nitrate level in the blood did not significantly change.Co-administration of ursodeoxycholic acid（UDCA） significantly antagonized the increase of nitrate in the liver resulted by administration of 1e.

Enoxacin-loaded Poly(lactic-co-glycolic acid) Coating on Porous Magnesium Scaffold as a Drug Delivery System: Antibacterial Properties and Inhibition of Osteoclastic Bone Resorption

Implant-associated infection remains a difficult medical problem in orthopedic surgery. Therefore, the development of multifunctional bone implants for treating infection and regenerating lost bone tissue, which may be a result of infection, is important. In the present study, we report the fabrication of enoxacin- loaded poly （lactic-co-glycolic acid） （PLGA） coating on porous magnesium scaffold （Enox-PLGA-Mg） which combine the favorable properties of magnesium, the antibacterial property and the effect of inhibition of osteoclastic bone resorption of enoxacin. The drug loaded PLGA coating of Mg scaffold enables higher drug loading efficiency （52%-56%） than non-coating enoxacin loaded Mg scaffold （Enox-Mg） （4%-5%）. Enox- PLGA-Mg exhibits sustained drug release for more than 14 days, and this controlled release of enoxacin signifcantly inhibits bacterial adhesion and prevented biofilm formation by Staphylococcus epidermidis （ATCC35984） and Staphylococcus aureus （ATCC25923）. Biocompatibility tests with Balb/c mouse embryo fibroblasts （Balb/c 3T3 cells） indicate that PLGA-Mg has better biocompatibility than Mg. Finally, we also demonstrate that Enox-PLCA-Mg extract potently inhibited osteoclast formation in vitro. Therefore, Enox- PLCA-Mg has the potential to be used as a multifunctional controlled drug delivery system bone scaffolds to prevent and/or treat orthopedic peri-implant infections.

Unlocking G-Quadruplexes as Targets and Tools against COVID-19

The applicability of G-quadruplexes(G4s)as antiviral targets,therapeutic agents and diagnostic tools for coronavirus disease 2019(COVID-19)is currently being evaluated,which has drawn the extensive attention of the scientific community.During the COVID-19 pandemic,research in this field is rapidly accumulating.In this review,we summarize the latest achievements and breakthroughs in the use of G4s as antiviral targets,therapeutic agents and diagnostic tools for COVID-19,particularly using G4 ligands.Finally,strength and weakness regarding G4s in anti-SARS-CoV-2 field are highlighted for prospective future projects.

Multifunctional nucleic acid nanostructures for gene therapies

Nucleic acid nanotechnology has been developed to be a promising strategy to construct various nano-biomaterials with structural programmability, spatial addressability, and excellent biocompatibility. Self-assembled nucleic acid nanostructures have been employed in a variety of biomedical applications, such as bio-imaging, diagnosis, and therapeutics. In this manuscript, we will review recent progress in the development of multifunctional nucleic acid nanostructures as gene drug delivery vehicles. Therapeutic systems based on RNA interference （RNAi）, clustered regularly interspaced short palindromic repeat associated proteins 9 system （CRISPR/Cas9） genome editing, gene expression, and CpG-based immunostimulation will be highlighted. We will also discuss the challenges and future directions of nucleic acid nanotechnology in biomedical research.

A New Highly-Enantioselective Synthetic Process for Producing (S)-2-Hydroxybutyric Acid Methyl Ester

（S）-2-aminobutyric acid being initial raw material,（S）-2-hydroxybutyric acid methyl ester was synthesized by means of a three step reaction of hydroxylation, salification and esterification. The product had a yield rate of 60.4%, purity of 99% and ee value higher than 99% by characterization of GC, HPLC and 1H NMR. This synthesis technique has advantages of high purity and ee value, low cost, short reaction time and mild reaction conditions so that it is suitable for production on industrial scale.