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J Tissue Eng Regen Med 2021 Apr 13. Epub 2021 Apr 13.

Biosystems Science and Engineering, Indian Institute of Science, Bangalore, 560012, India.

Although several advances have been made in the field of medicine during the last few decades, yet targeted delivery of biomolecules is still a significant challenge. Thus present study illustrates the fabrication of dual nature magneto-conducting Fe O - SU8 derived carbon-based Janus microbots that could deliver biomolecules efficiently inside cells. These possess dual properties, i. Read More

J Control Release 2021 Apr 9. Epub 2021 Apr 9.

Departments of Chemistry, Chemical Engineering, and Materials Science & Engineering, Texas A&M University, College Station, TX 77842, USA. Electronic address:

Zwitterionic polymer nanoparticles of diverse morphologies (spherical, cylindrical, and platelet-like) constructed from biocompatible sugar-based polymers are designed to extend the pharmacological activities of short- and long-acting insulin peptides, thereby providing potential for therapeutic systems capable of reducing the frequency of administration and improving patient compliance. Amphiphilic block copolymers composed of zwitterionic poly(d-glucose carbonate) and semicrystalline polylactide segments were synthesized, and the respective block length ratios were tuned to allow formation of nanoscopic assemblies having different morphologies. Insulin-loaded nanoparticles had similar sizes and morphologies to the unloaded nanoparticle counterparts. Read More

Adv Drug Deliv Rev 2021 Apr 9. Epub 2021 Apr 9.

Wuya College of Innovation, Shenyang Pharmaceutical University, Wenhua Road No. 103, 110016 Shenyang, China; Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark. Electronic address:

The global market of pharmaceutical biologics has expanded significantly during the last few decades and currently, pharmaceutical biologic products constitute anindispensable part of the modern medicines. Most pharmaceutical biologic products are injections either in solutions or lyophilized powders because of their low oral bioavailability. There are certain pharmaceutical biologic entities formulated into particulate delivery systems for the administration via non-invasive routes or to achieve prolonged pharmaceutical actions to reduce the frequency of injections. Read More

Front Immunol 2021 25;12:641563. Epub 2021 Mar 25.

Laboratory of General Pathology, Department of Medicine and Surgery, University of Parma, Parma, Italy.

At present, the central role played by arginine in the modulation of the inflammatory cellular responses is well-recognized, and many pro-inflammatory stimuli are known to modulate the expression and activity of its transmembrane transporters. In this regard, we have addressed the effects of bacterial flagellin from (FLA-PA) on the uptake of the amino acid in human epithelial respiratory cells. Among the arginine transporters, only ATB, yL, and y were operative in bronchial epithelial Calu-3 cells under control conditions; however, only the expression and activity of ATB were stimulated upon incubation with flagellin, whereas those of systems yL and y were not stimulated. Read More

Bioorg Med Chem 2021 Mar 19;38:116111. Epub 2021 Mar 19.

Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.

Cell-penetrating peptides (CPPs) have been attracting attention as tools for intracellular delivery of membrane-impermeant functional molecules. Among the variety of CPPs that have been developed, many are composed of both natural and unnatural amino acids. We previously synthesized α,α-disubstituted α-amino acids (dAAs) containing a five-membered carbocyclic ring in its side chain and revealed the utility of dAAs for the development of novel CPPs. Read More

Eur J Pharm Biopharm 2021 Apr 7. Epub 2021 Apr 7.

Centre for Marine Sciences, Universidade do Algarve, 8005-139 Faro, Portugal; Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal. Electronic address:

Tuberculosis remains a leading cause of death, therapeutic failure being mainly due to non-compliance with prolonged treatments, often associated with severe side-effects. New therapeutic strategies are demanded and, considering that the lung is the primary site of infection, direct lung delivery of antibiotics is possibly an effective approach. Therapeutic success in this context depends on suitable carriers that reach the alveoli where Mycobacterium hosts (macrophages) reside, as well as on their ability to promote macrophage capture and intracellular accumulation of drugs. Read More

Mol Cell 2021 Apr 4. Epub 2021 Apr 4.

Université de Paris, CNRS, Institut Jacques Monod, 75006 Paris, France. Electronic address:

mRNA translation is coupled to multiprotein complex assembly in the cytoplasm or to protein delivery into intracellular compartments. Here, by combining systematic RNA immunoprecipitation and single-molecule RNA imaging in yeast, we have provided a complete depiction of the co-translational events involved in the biogenesis of a large multiprotein assembly, the nuclear pore complex (NPC). We report that binary interactions between NPC subunits can be established during translation, in the cytoplasm. Read More

ACS Appl Mater Interfaces 2021 Apr 9. Epub 2021 Apr 9.

Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, People's Republic of China.

Natural killer (NK) cell-based immunotherapy presents a promising antitumor strategy and holds potential for combination with chemotherapy. However, the suppressed NK cell activity and poor tumor retention of therapeutics hinder the efficacy. To activate NK cell-based immuno-chemotherapy and enhance the tumor retention, we proposed a pH-responsive self-aggregated nanoparticle for the codelivery of chemotherapeutic doxorubicin (DOX) and the transforming growth factor-β (TGF-β)/Smad3 signaling pathway inhibitor SIS3. Read More

Hua Xi Kou Qiang Yi Xue Za Zhi 2021 Apr;39(2):136-142

Orofacial Reconstruction and Regeneration Laboratory, School of Stomatology of Southwest Medical University, Luzhou 646000, China.

Objectives: This study aims to construct endogenous exosomes abundantly loaded with miR-1 and investigate the role of exosome-mediated microRNA-1 (miR-1) delivery on CAL-27 cell proliferation.

Methods: Exosomes secreted by miR-1-overexpressing HEK293 cells (miR1-EXO) were purified via ultracentrifugation and subjected to transmission electron microscopy, nanoparticle analysis, Western blot analysis, and quantitative polymerase chain reaction (qPCR). CAL-27 cells were cocultured with exosomes secreted by HEK293 cells (CON-EXO) and miR1-EXO and equivalent phosphate buffer saline. Read More

Front Chem 2021 23;9:645297. Epub 2021 Mar 23.

Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.

The intracellular delivery of emerging biomacromolecular therapeutics, such as genes, peptides, and proteins, remains a great challenge. Unlike small hydrophobic drugs, these biotherapeutics are impermeable to the cell membrane, thus relying on the endocytic pathways for cell entry. After endocytosis, they are entrapped in the endosomes and finally degraded in lysosomes. Read More

Int J Nanomedicine 2021 30;16:2569-2584. Epub 2021 Mar 30.

Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun, 130012, People's Republic of China.

Background: Multidrug resistance (MDR) has emerged to be a major hindrance in cancer therapy, which contributes to the reduced sensitivity of cancer cells toward chemotherapeutic drugs mainly owing to the over-expression of drug efflux transporters. The combination of gene therapy and chemotherapy has been considered as a potential approach to improve the anti-cancer efficacy by reversing the MDR effect.

Materials And Methods: The AS1411 aptamer-functionalized micelles were constructed through an emulsion/solvent evaporation strategy for the simultaneous co-delivery of doxorubicin and miR-519c. Read More

Biochemistry (Mosc) 2021 Feb;86(2):217-229

Blokhin National Medical Research Center of Oncology, Moscow, 115478, Russia.

Retinoic acid (RA) binding proteins, CRABP1 and CRABP2, are molecular chaperones that mediate intracellular activity of RA, the key promoter of cell differentiation with tumor suppressor activity. One of the main functions of CRABP2 is delivery and transfer of RA to the nuclear receptors RAR/RXR, which leads to activation of the transcription of a wide range of retinoid-responsive genes. The functions of CRABP1 are less studied but are apparently associated with sequestration of RA in cytoplasm and limitation of its transcriptional activity, suggesting involvement of this protein in the development of RA resistance. Read More

Zhonghua Bing Li Xue Za Zhi 2021 Apr;50(4):417-420

Department of Pathology, the First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China.

Nano Lett 2021 Apr 8. Epub 2021 Apr 8.

Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China.

The genetic heterogeneities in cancer cells pose challenges to achieving precise drug treatment in a widely applicable manner. Most single-cell gene analysis methods rely on cell lysis for gene extraction and identification, showing limited capacity to provide the correlation of genetic properties and real-time cellular behaviors. Here, we report a single living cell analysis nanoplatform that enables interrogating gene properties and drug resistance in millions of single cells. Read More

JCI Insight 2021 Apr 8;6(7). Epub 2021 Apr 8.

Department of Dermatology and.

The Janus kinase/signal transducers and activators of transcription (JAK/STAT) are key intracellular mediators in the signal transduction of many cytokines and growth factors. Common γ chain cytokines and interferon-γ that use the JAK/STAT pathway to induce biological responses have been implicated in the pathogenesis of alopecia areata (AA), a T cell-mediated autoimmune disease of the hair follicle. We previously showed that therapeutic targeting of JAK/STAT pathways using the first-generation JAK1/2 inhibitor, ruxolitinib, and the pan-JAK inhibitor, tofacitinib, was highly effective in the treatment of human AA, as well as prevention and reversal of AA in the C3H/HeJ mouse model. Read More