bims-drudre Biomed News
on Targeted drug delivery and programmed release mechanisms
Issue of 2022‒09‒18
seventeen papers selected by
Ceren Kimna
Technical University of Munich
  1. Augmented DNA Nano-Architectures: A Structural Library of 3D Self-Assembling Tensegrity Triangle Variants.
  2. Microgel reinforced zwitterionic hydrogel coating for blood-contacting biomedical devices.
  3. Programming Dissipation Systems by DNA Timer for Temporally Regulating Enzyme Catalysis and Nanostructure Assembly.
  4. Treating Multi-Drug-Resistant Bacterial Infections by Functionalized Nano-Bismuth Sulfide through the Synergy of Immunotherapy and Bacteria-Sensitive Phototherapy.
  5. Computer-Aided Design of Lasso-like Self-Assembling Anticancer Peptides with Multiple Functions for Targeted Self-Delivery and Cancer Treatments.
  6. Cationic polymer synergizing with a disulfide-containing enhancer achieved efficient nucleic acid and protein delivery.
  7. Single-component hyaluronic acid hydrogel adhesive based on phenylboronic ester bonds for hemostasis and wound closure.
  8. Outer Membrane Vesicles as Molecular Biomarkers for Gram-negative Sepsis: Taking Advantage of Nature's Perfect Packages.
  9. Hypoxia-Activated PEGylated Paclitaxel Prodrug Nanoparticles for Potentiated Chemotherapy.
  10. Implanted synthetic cells trigger tissue angiogenesis through de novo production of recombinant growth factors.
  11. Polydopamine-engineered Theranostic Nanoscouts Enabling Intracellular HSP90 mRNAs Fluorescence Detection for Imaging-Guided Chemo-Photothermal Therapy.
  12. Construction of Active Protein Materials: Manipulation on Morphology of Salmon Calcitonin Assemblies with Enhanced Bone Regeneration Effect.
  13. Tumor immunosuppressive microenvironment modulating hydrogels for second near-infrared photothermal-immunotherapy of cancer.
  14. Systematic assessment of microRNAs associated with lung cancer and physical exercise.
  15. Unprotonatable and ROS-Sensitive Nanocarrier for NIR Spatially Activated siRNA Therapy with Synergistic Drug Effect.
  16. Soft Human-Machine Interface Sensing Displays: Materials and Devices.
  17. Living material assembly of bacteriogenic protocells.
  1. Adv Mater. 2022 Sep 13. e2206876
    Augmented DNA Nano-Architectures: A Structural Library of 3D Self-Assembling Tensegrity Triangle Variants.
    Karol Woloszyn, Simon Vecchioni, Yoel P Ohayon, Brandon Lu, Yinglun Ma, Qiuyan Huang, Eric Zhu, Daniel Chernovolenko, Tiffany Markus, Nataša Jonoska, Chengde Mao, Nadrian C Seeman, Ruojie Sha.
      The DNA tensegrity triangle is known to reliably self-assemble into a 3D rhombohedral crystalline lattice via sticky-end cohesion. Here, we expand the library of accessible motifs through (1) covalent extensions of inter-triangle regions and (2) sticky-end coordinated linkages of adjacent triangles with double helical segments using both geometrically symmetric and asymmetric configurations. We report the molecular structures of eighteen self-assembled architectures at resolutions of 3.32-9.32 Å; the observed cell dimensions, cavity sizes, and cross-sectional areas agree with theoretical expectations. These data demonstrate that fine control over triclinic and rhombohedral crystal parameters and the customizability of more complex 3D DNA lattices are attainable via rational design. We anticipate that augmented DNA architectures may be fine-tuned for the self-assembly of designer nano-cages, guest-host complexes, and proscriptive 3D nanomaterials, as originally envisioned. Finally, designer asymmetric crystalline building blocks can be seen as a first step toward controlling and encoding information in three dimensions. This article is protected by copyright. All rights reserved.
    Keywords:  DNA crystals; DNA nanotechnology; nano-architectures; self-assembly; tensegrity triangles
    DOI:  https://doi.org/10.1002/adma.202206876
  2. Nat Commun. 2022 Sep 12. 13(1): 5339
    Microgel reinforced zwitterionic hydrogel coating for blood-contacting biomedical devices.
    Mengmeng Yao, Zhijian Wei, Junjin Li, Zhicheng Guo, Zhuojun Yan, Xia Sun, Qingyu Yu, Xiaojun Wu, Chaojie Yu, Fanglian Yao, Shiqing Feng, Hong Zhang, Junjie Li.
      Zwitterionic hydrogels exhibit eminent nonfouling and hemocompatibility. Several key challenges hinder their application as coating materials for blood-contacting biomedical devices, including weak mechanical strength and low adhesion to the substrate. Here, we report a poly(carboxybetaine) microgel reinforced poly(sulfobetaine) (pCBM/pSB) pure zwitterionic hydrogel with excellent mechanical robustness and anti-swelling properties. The pCBM/pSB hydrogel coating was bonded to the PVC substrate via the entanglement network between the pSB and PVC chain. Moreover, the pCBM/pSB hydrogel coating can maintain favorable stability even after 21 d PBS shearing, 0.5 h strong water flushing, 1000 underwater bends, and 100 sandpaper abrasions. Notably, the pCBM/pSB hydrogel coated PVC tubing can not only mitigate the foreign body response but also prevent thrombus formation ex vivo in rats and rabbits blood circulation without anticoagulants. This work provides new insights to guide the design of pure zwitterionic hydrogel coatings for biomedical devices.
    DOI:  https://doi.org/10.1038/s41467-022-33081-7
  3. ACS Nano. 2022 Sep 14.
    Programming Dissipation Systems by DNA Timer for Temporally Regulating Enzyme Catalysis and Nanostructure Assembly.
    Zhaohui Qin, Yu Liu, Linghao Zhang, Jiajia Liu, Xin Su.
      Live cells precisely control their temporal pattern in energy dissipative processes such as catalysis and assembly. Here, we demonstrate a DNA-based artificial dissipative nonequilibrium system where the transient state is controlled by the processive digestion of λ-exonuclease (λ Exo). This enzyme reaction serves as an orthogonal and independent molecular timer allowing for the programmable regulation of the transient-state lifetime. This dissipation system is concatenated to enzyme catalysis and nanostructure assembly networks. Dynamic activation of enzyme catalysis and dynamic disassembly of DNA nanotubes (DNT) are realized, and the state lifetimes of these systems are accurately encoded by the DNA timer. This work demonstrates nontrivial dissipation systems with built-in molecular timers, which can be a useful tool for developing artificial reaction networks and nanostructures with enhanced complexities and intelligence.
    Keywords:  DNA nanostructure assembly; Dissipative DNA nanotechnology; Enzyme catalysis; Molecular timer; λ-Exonuclease
    DOI:  https://doi.org/10.1021/acsnano.2c04405
  4. ACS Nano. 2022 Sep 12.
    Treating Multi-Drug-Resistant Bacterial Infections by Functionalized Nano-Bismuth Sulfide through the Synergy of Immunotherapy and Bacteria-Sensitive Phototherapy.
    Yuan Li, Xiangmei Liu, Zhenduo Cui, Yufeng Zheng, Hui Jiang, Yu Zhang, Yanqin Liang, Zhaoyang Li, Shengli Zhu, Shuilin Wu.
      Owing to its flexibility and high treatment efficiency, phototherapy is rapidly emerging for treating bacteria-induced diseases, but how to improve the sensitivity of bacteria to reactive oxygen species (ROS) and heat simultaneously to kill bacteria under mild conditions is still a challenge. Herein, we designed a NIR light catalyst (Bi2S3-S-nitrosothiol-acetylcholine (BSNA)) by transforming •O2- into peroxynitrite in situ, which can enhance the bacterial sensibility to ROS and heat and kill bacteria under a mild temperature. The transformed peroxynitrite in situ possessed a stronger ability to penetrate cell membranes and antioxidant capacity. The BSNA nanoparticles (NPs) inhibited the bacterial glucose metabolic process through down-regulated xerC/xerD expression and disrupted the HSP70/HSP90 secondary structure through nitrifying TYR179. Additionally, the synergistic effect of the designed BSNA and clinical antibiotics increased the antibacterial activity. In the case of tetracycline-class antibiotics, BSNA NPs induced phenolic hydroxyl group structure changes and inhibited the interaction between tetracycline and targeted t-RNA recombinant protein. Besides, BSNA stimulated production of more CD8+ T cells and reduced common complications in peritonitis, which provided immunotherapy activity. The targeted and anti-infective effect of BSNA suggested that we propose a nanotherapeutic strategy to achieve more efficient synergistic therapy under mild temperatures.
    Keywords:  antibacterial; bismuth sulfide; multi-drug-resistant bacteria; peritonitis; phototherapy
    DOI:  https://doi.org/10.1021/acsnano.2c05756
  5. ACS Nano. 2022 Sep 13.
    Computer-Aided Design of Lasso-like Self-Assembling Anticancer Peptides with Multiple Functions for Targeted Self-Delivery and Cancer Treatments.
    Pengfei Pei, Long Chen, Ruru Fan, Xi-Rui Zhou, Shan Feng, Hangrui Liu, Quanqiang Guo, Huiwei Yin, Qiang Zhang, Fude Sun, Liang Peng, Peng Wei, Chengzhi He, Renzhong Qiao, Zai Wang, Shi-Zhong Luo.
      Anticancer peptides are promising drug candidates for cancer treatment, but the short circulation time and low delivery efficiency limit their clinical applications. Herein, we designed several lasso-like self-assembling anticancer peptides (LASAPs) integrated with multiple functions by a computer-aided approach. Among these LASAPs, LASAP1 (CRGDKGPDCGKAFRRFLGALFKALSHLL, 1-9 disulfide bond) was determined to be superior to the others because it can self-assemble into homogeneous nanoparticles and exhibits improved stability in serum. Thus, LASAP1 was chosen for proving the design idea. LASAP1 can self-assemble into nanoparticles displaying iRGD on the surface because of its amphiphilic structure and accumulate to the tumor site after injection because of the EPR effect and iRGD targeting to αVβ3 integrin. The nanoparticles could disassemble in the acidic microenvironment of the solid tumor, and cleaved by the overexpressed hK2, which was secreted by prostate tumor cells, to release the effector peptide PTP-7b (FLGALFKALSHLL), which was further activated by the acidic pH. Therefore, LASAP1 could target the orthotopic prostate tumor in the model mice after intraperitoneal injection and specifically inhibit tumor growth, with low systematic toxicity. Combining the multiple targeting functions, LASAP1 represents a promising design of self-delivery of peptide drugs for targeted cancer treatments.
    Keywords:  anticancer peptide; multitargeting; nanoparticle; self-assembling; self-delivery
    DOI:  https://doi.org/10.1021/acsnano.2c01014
  6. Biomater Sci. 2022 Sep 15.
    Cationic polymer synergizing with a disulfide-containing enhancer achieved efficient nucleic acid and protein delivery.
    Yuanji Feng, Zhaopei Guo, Jie Chen, Sijia Zhang, Jiayan Wu, Huayu Tian, Xuesi Chen.
      To improve the efficiency of nucleic acid and protein delivery by cationic polymers, there is a trade-off between increasing the positive charge density of cationic polymers and decreasing cytotoxicity. In this work, a strategy to introduce multiple interactions between the cell membrane and a delivery system based on cationic polymers was proposed. A novel delivery system consisting of PEI1.8k and an enhancer (LA-RT) was fabricated. The introduction of LA-RT contributed to multiple interactions between the delivery system and the cell membrane including electrostatic interactions, hydrogen bonding, hydrophobic interaction, and dynamic sulfur exchange reactions, which enabled efficient intracellular delivery of nucleic acids and proteins. For nucleic acid delivery, plasmid DNA and mRNA were loaded to realize CRISPR/Cas 9 gene editing in vivo and protein expression in vivo, respectively. For protein delivery, the delivery system carrying OVA protein and CpG formed a nano-vaccine, which induced enhanced humoral and cellular immunity in vivo. In addition, the delivery system based on PEI1.8k revealed negligible cytotoxicity. This work provided a novel strategy to prepare efficient delivery systems based on cationic polymers via the introduction of a multifunctional enhancer.
    DOI:  https://doi.org/10.1039/d2bm01211a
  7. Carbohydr Polym. 2022 Nov 15. pii: S0144-8617(22)00858-X. [Epub ahead of print]296 119953
    Single-component hyaluronic acid hydrogel adhesive based on phenylboronic ester bonds for hemostasis and wound closure.
    Ming Li, Xinglei Shi, Bo Yang, Jiajun Qin, Xiaobao Han, Wanjia Peng, Yiyan He, Hongli Mao, Deling Kong, Zhongwei Gu.
      Hydrogel tissue adhesives that currently available are often fabricated by mixing two or more polymeric components. Single-component hydrogels afford injectability, strong and reversible adhesion remain a formidable challenge. This research describes the creation of the first single-component hyaluronic acid hydrogel adhesive-based on phenylboronic acid-diol ester linkages. Phenylboronic acid can not only serve as a cross-linker to form hydrogel, but also act as an adhesion site for glycosyl compounds found in biological cell membranes. The rheological and compressive tests for the hydrogel show that it has excellent self-healing properties, good injectability and strong compressive strength. Adhesion tests demonstrated that the hydrogel has significantly greater adhesion strength than commercial fibrin glue. These findings suggest that the rational design of hydrogel precursors facilitates the formation of single-component networks and multiple functionalities. In vivo studies further proved the hydrogel was an ideal bio-adhesive with biocompatibility, absorbed wound exudate and hemostasis, and accelerated wound closure.
    Keywords:  Hemostasis; Hyaluronic acid; Hydrogels; Single-component; Tissue adhesive; Wound closure
    DOI:  https://doi.org/10.1016/j.carbpol.2022.119953
  8. J Biol Chem. 2022 Sep 12. pii: S0021-9258(22)00926-7. [Epub ahead of print] 102483
    Outer Membrane Vesicles as Molecular Biomarkers for Gram-negative Sepsis: Taking Advantage of Nature's Perfect Packages.
    Lea Vacca Michel, Thomas Gaborski.
      Sepsis is an often life-threatening response to infection, occurring when host pro-inflammatory immune responses become abnormally elevated and dysregulated. To diagnose sepsis, the patient must have a confirmed or predicted infection, as well as other symptoms associated with the pathophysiology of sepsis. However, a recent study found that a specific causal organism could not be determined in the majority (70.1%) of sepsis cases, likely due to aggressive antibiotics or localized infections. The timing of a patient's sepsis diagnosis is often predictive of their clinical outcome, underlining the need for a more definitive molecular diagnostic test. Here, we outline the advantages and challenges to using bacterial outer membrane vesicles (OMVs), nanoscale spherical buds derived from the outer membrane of Gram-negative bacteria, as a diagnostic biomarker for Gram-negative sepsis. Advantages include OMV abundance, their robustness in the presence of antibiotics, and their unique features derived from their parent cell that could allow for differentiation between bacterial species. Challenges include the rigorous purification methods required to isolate OMVs from complex biofluids and the additional need to separate OMVs from similarly-sized extracellular vesicles, which can share physical properties with OMVs.
    Keywords:  Gram-negative bacteria; antibiotics; biomarker; extracellular vesicles; outer membrane; outer membrane vesicles; sepsis
    DOI:  https://doi.org/10.1016/j.jbc.2022.102483
  9. ACS Nano. 2022 Sep 16.
    Hypoxia-Activated PEGylated Paclitaxel Prodrug Nanoparticles for Potentiated Chemotherapy.
    Dengyuan Hao, Qian Meng, Bowen Jiang, Shaojin Lu, Xiujuan Xiang, Qing Pei, Haijun Yu, Xiabin Jing, Zhigang Xie.
      Developing controlled drug-release systems is imperative and valuable for increasing the therapeutic index. Herein, we synthesized hypoxia-responsive PEGylated (PEG = poly(ethylene glycol)) paclitaxel prodrugs by utilizing azobenzene (Azo) as a cleavable linker. The as-fabricated prodrugs could self-assemble into stable nanoparticles (PAP NPs) with high drug content ranging from 26 to 44 wt %. The Azo group in PAP NPs could be cleaved at the tumorous hypoxia microenvironment and promoted the release of paclitaxel for exerting cytotoxicity toward cancer cells. In addition, comparative researches revealed that the PAP NPs with the shorter methoxy-PEG chain (molecular weight = 750) possessed enhanced tumor suppression efficacy and alleviated off-target toxicity. Our work demonstrates a promising tactic to develop smart and simple nanomaterials for disease treatment.
    Keywords:  PEGylation; hypoxia-responsive; paclitaxel; prodrugs; self-assembly
    DOI:  https://doi.org/10.1021/acsnano.2c05341
  10. Proc Natl Acad Sci U S A. 2022 Sep 20. 119(38): e2207525119
    Implanted synthetic cells trigger tissue angiogenesis through de novo production of recombinant growth factors.
    Gal Chen, Rotem Levin, Shira Landau, Maya Kaduri, Omer Adir, Iris Ianovici, Nitzan Krinsky, Ofri Doppelt-Flikshtain, Jeny Shklover, Janna Shainsky-Roitman, Shulamit Levenberg, Avi Schroeder.
      Progress in bottom-up synthetic biology has stimulated the development of synthetic cells (SCs), autonomous protein-manufacturing particles, as dynamic biomimetics for replacing diseased natural cells and addressing medical needs. Here, we report that SCs genetically encoded to produce proangiogenic factors triggered the physiological process of neovascularization in mice. The SCs were constructed of giant lipid vesicles and were optimized to facilitate enhanced protein production. When introduced with the appropriate genetic code, the SCs synthesized a recombinant human basic fibroblast growth factor (bFGF), reaching expression levels of up to 9⋅106 protein copies per SC. In culture, the SCs induced endothelial cell proliferation, migration, tube formation, and angiogenesis-related intracellular signaling, confirming their proangiogenic activity. Integrating the SCs with bioengineered constructs bearing endothelial cells promoted the remodeling of mature vascular networks, supported by a collagen-IV basement membrane-like matrix. In vivo, prolonged local administration of the SCs in mice triggered the infiltration of blood vessels into implanted Matrigel plugs without recorded systemic immunogenicity. These findings emphasize the potential of SCs as therapeutic platforms for activating physiological processes by autonomously producing biological drugs inside the body.
    Keywords:  angiogenesis; artificial cells; cell-free; targeted drug delivery; tissue engineering
    DOI:  https://doi.org/10.1073/pnas.2207525119
  11. Adv Healthc Mater. 2022 Sep 13. e2201615
    Polydopamine-engineered Theranostic Nanoscouts Enabling Intracellular HSP90 mRNAs Fluorescence Detection for Imaging-Guided Chemo-Photothermal Therapy.
    Geng Yang, Mengyue Li, Ting Song, Xiangyan Chen, Hanxi Zhang, Xiaodan Wei, Ningxi Li, Tingting Li, Xiang Qin, Shun Li, Fengming You, Chunhui Wu, Wei Zhang, Yiyao Liu, Hong Yang.
      The combination of photothermal therapy (PTT) and chemotherapy is considered a promising tumor treatment modality, nevertheless, cellular resistance induced by heat shock proteins (HSPs) overexpressed in tumor cells will restrict the therapeutic effect. Herein, we propose a multifunctional nanobeacon DOX/HCuS@PDA-MB (D/CP-MB) with a scout function for HSP90 mRNA fluorescence detection and near-infrared (NIR) triggered drug release for sensitizing chemo-photothermal therapy. In the theranostic nanobeacons, HSP90-MBs not only enable fluorescence detection of intracellular HSP90 mRNAs, but also down-regulate the expression of HSP90 to reduce cell resistance. With the assistance of NIR and guidance of fluorescence imaging, spatiotemporal doxorubicin release can be achieved by the trigger of the photothermal effect, allowing for combined chemotherapy and photothermal treatment. Furthermore, the dual-photothermal effect of HCuS and polydopamine will lead to a better photothermal effect. Moreover, compared with other control groups, D/CP-MB nanobeacons exhibit effective boost therapeutic efficacy by inducing significant suppression of tumor proliferation and enhancement of apoptosis both in vitro and in vivo. In summary, this work provides novel theranostic nanobeacons that integrate imaging and therapy in a single nanoparticle, this strategy of imaging-guided therapy can enable precise tumor treatment and effectively improve tumor treatment efficacy. This article is protected by copyright. All rights reserved.
    Keywords:  chemotherapy; fluorescence detection; heat shock protein; photothermal therapy; sensitivity
    DOI:  https://doi.org/10.1002/adhm.202201615
  12. Adv Mater. 2022 Sep 14. e2207526
    Construction of Active Protein Materials: Manipulation on Morphology of Salmon Calcitonin Assemblies with Enhanced Bone Regeneration Effect.
    Libin Wu, Liang Cheng, Jing Yang, Yufei Yan, Ensong Zhang, Zdravko Kochovski, Long Li, Zhen Wang, Lianfu Deng, Yan Lu, Pol Besenius, Wenguo Cui, Guosong Chen.
      The effect of protein drugs is always limited by their relatively low stability and fast degradation property, thus various elegant efforts have been made to improve the bioactivity and biocompatibility of the protein drugs. In this paper, we propose an alternative way to solve this problem. By simply adding a limited amount of small molecular regulator, which tunes the subtle balance of protein-protein interactions and disulfide bond formation, the self-assembly property of the protein drug could be regulated, forming an active protein material itself. This means that, the resulting biomaterial is dominated by the protein drug and water, with significantly enhanced bone regeneration effect compared to the virgin protein in vitro and in vivo, through multivalent effect between the protein and receptor and the retarded degradation of the assembled proteins. In this active protein material, the protein drug is not only the active drug, but also the drug carrier, which greatly increased the drug-loading efficiency of the biomaterial, indicating the advantages of easy preparation, high efficiency and low cost of the active protein material with bright future in biomedical applications. This article is protected by copyright. All rights reserved.
    Keywords:  active protein material; bone regeneration; morphology manipulation
    DOI:  https://doi.org/10.1002/adma.202207526
  13. Mater Today Bio. 2022 Dec;16 100416
    Tumor immunosuppressive microenvironment modulating hydrogels for second near-infrared photothermal-immunotherapy of cancer.
    Junjian Shen, Minghui Lin, Mengbin Ding, Ningyue Yu, Chun Yang, Deping Kong, Haitao Sun, Zongyu Xie.
      Immunotherapy has recently been seen as a hopeful therapeutic device to inhibit tumor growth and metastasis, while the curative efficacy is limited by intrinsic immunosuppressive tumor microenvironment. Herein, we reported a tumor immunosuppressive microenvironment modulating hydrogel (TIMmH) platform to achieve second near-infrared (NIR-II) photothermal therapy (PTT) combined immunotherapy for durable inhibition of breast cancer. This TIMmH platform was synthesized through co-loading of NIR-II photothermal nanoagent and an immunoadjuvant cytosine-phosphateguanosine oligodeoxynucleotides (CpG ODNs) into the alginate hydrogel (ALG). Upon the administration of ALG into the tumor, the TIMmH was in situ formed via the coordination effect with Ca2+, locally encapsulating the semiconducting polymer nanoparticles (SPIIN) and CpG in the colloid, achieving to prolong the accumulation time and prevent the premature damage and release of immunotherapeutic agents. Upon 1064-nm photoirradiation, the TIMmHSD was able to elevate the intratumoral temperature for the ablation of tumors, which could induce the apoptosis of tumor cells and achieve thermal immune activation by regulating of an immunosuppressive microenvironment. The TIMmH-mediated combined treatment effectively suppressed the growths of breast cancers, and even acquired a sustained inhibition of the lung metastasis. This study provides a novel tumor immunosuppressive microenvironment modulating hydrogel platform with NIR-II photoexcited capacity for the safe, effective and durable lung metastasis-inhibiting breast cancer treatment.
    Keywords:  Breast cancer; Hydrogels; Immunotherapy; Metastasis; Photothermal therapy
    DOI:  https://doi.org/10.1016/j.mtbio.2022.100416
  14. Front Oncol. 2022 ;12 917667
    Systematic assessment of microRNAs associated with lung cancer and physical exercise.
    Yang Liu, Libo He, Wang Wang.
      It has long been evident that physical exercise reduces the risk of cancer and improves treatment efficacy in tumor patients, particularly in lung cancer (LC). Several molecular mechanisms have been reported, but the mechanisms related to microRNAs (miRNAs) are not well understood. MiRNAs modulated various basic biological processes by negatively regulating gene expression and can be transmitted between cells as signaling molecules. Recent studies have shown that miRNAs are actively released into the circulation during exercise, and are deeply involved in cancer pathology. Hence, the role of exercise intervention in LC treatment may be further understood by identifying miRNAs associated with LC and physical activity. Here, miRNAs expression datasets related to LC and exercise were collected to screen altered miRNAs. Further bioinformatic approaches were performed to analyze the value of the selected miRNAs. The results identified 42 marker miRNAs in LC, of which three core-miRNAs (has-miR-195, has-miR-26b, and has-miR-126) were co-regulated by exercise and cancer, mainly involved in cell cycle and immunity. Our study supports the idea that using exercise intervention as adjuvant therapy for LC patients. These core-miRNAs, which are down-regulated in cancer but elevated by exercise, may act as suppressors in LC and serve as non-invasive biomarkers for cancer prevention.
    Keywords:  bioinformatics; lung cancer; microRNA; physical exercise; prognosis
    DOI:  https://doi.org/10.3389/fonc.2022.917667
  15. Small. 2022 Sep 12. e2203823
    Unprotonatable and ROS-Sensitive Nanocarrier for NIR Spatially Activated siRNA Therapy with Synergistic Drug Effect.
    Shaohui Deng, Shiyin Wang, Zecong Xiao, Du Cheng.
      Although small interfering RNA (siRNA) therapy has achieved great progress, unwanted gene inhibition in normal tissues severely limits its extensive clinical applications due to uncontrolled siRNA biodistribution. Herein, a spatially controlled siRNA activation strategy is developed to achieve tumor-specific siRNA therapy without gene inhibition in the normal tissues. The quaternary ammonium moieties are conjugated to amphiphilic copolymers via reactive oxygen species (ROS)-sensitive thioketal (TK) linkers for co-delivery of siRNA and photosensitizer chlorin e6 (Ce6), showing excellent siRNA complexation capacity and near infrared (NIR)-controlled siRNA release. In the normal tissue, siRNAs are trapped and degraded in the endo-lysosomes due to the unprotonatable property of quaternary ammonium moiety, showing the siRNA activity "off" state. When NIR irradiation is spatially applied to the tumor tissue, the NIR irradiation/Ce6-induced ROS trigger siRNA endo-lysosomal escape and cytosolic release through the photochemical internalization effect and cleavage of TK bonds, respectively, showing the siRNA activity "on" state. The siRNA-mediated glutathione peroxidase 4 gene inhibition enhances ROS accumulation. The synergistic antitumor activity of Ce6 photodynamic therapy and gene inhibition is confirmed in vivo. Spatially controlled tumor-specific siRNA activation and co-delivery with Ce6 using unprotonatable and ROS-sensitive cationic nanocarriers provide a feasible strategy for tumor-specific siRNA therapy with synergistic drug effects.
    Keywords:  combined therapy; photodynamic therapy; spatially controlled endo-lysosomal escape; spatially controlled siRNA release; tumor-specific siRNA therapy; unprotonatable cationic micelles
    DOI:  https://doi.org/10.1002/smll.202203823
  16. Adv Mater. 2022 Sep 12. e2204964
    Soft Human-Machine Interface Sensing Displays: Materials and Devices.
    Seunggun Yu, Tae Hyun Park, Wei Jiang, Seung Won Lee, Eui Hyuk Kim, Seokyeong Lee, Jung-Eun Park, Cheolmin Park.
      The development of human-interactive sensing displays (HISDs) that simultaneously detect and visualize stimuli is important for numerous cutting-edge human-machine interface technologies. Therefore, innovative device platforms with optimized architectures of HISDs combined with novel high-performance sensing and display materials are demonstrated. This study comprehensively reviews the recent advances in HISDs, particularly the device architectures that enable scaling-down and simplifying the HISD, as well as material designs capable of directly visualizing input information received by various sensors. Various HISD platforms for integrating sensors and displays are described. HISDs consist of a sensor and display connected through a microprocessor, and attempts to assemble the two devices by eliminating the microprocessor are detailed. Single-device HISD technologies are highlighted in which input stimuli acquired by sensory components are directly visualized with various optical components, such as electroluminescence, mechanoluminescence, and structural color. The review forecasts future HISD technologies that demand the development of materials with molecular-level synthetic precision that enables simultaneous sensing and visualization. Furthermore, emerging HISDs combined with artificial intelligence technologies and those enabling simultaneous detection and visualization of extrasensory information are discussed. This article is protected by copyright. All rights reserved.
    Keywords:  electroluminescence; flexible sensing displays; human-interactive sensing displays; mechanoluminescence; soft human-machine interface; structural color
    DOI:  https://doi.org/10.1002/adma.202204964
  17. Nature. 2022 Sep 14.
    Living material assembly of bacteriogenic protocells.
    Can Xu, Nicolas Martin, Mei Li, Stephen Mann.
      Advancing the spontaneous bottom-up construction of artificial cells with high organizational complexity and diverse functionality remains an unresolved issue at the interface between living and non-living matter1-4. Here, to address this challenge, we developed a living material assembly process based on the capture and on-site processing of spatially segregated bacterial colonies within individual coacervate microdroplets for the endogenous construction of membrane-bounded, molecularly crowded, and compositionally, structurally and morphologically complex synthetic cells. The bacteriogenic protocells inherit diverse biological components, exhibit multifunctional cytomimetic properties and can be endogenously remodelled to include a spatially partitioned DNA-histone nucleus-like condensate, membranized water vacuoles and a three-dimensional network of F-actin proto-cytoskeletal filaments. The ensemble is biochemically energized by ATP production derived from implanted live Escherichia coli cells to produce a cellular bionic system with amoeba-like external morphology and integrated life-like properties. Our results demonstrate a bacteriogenic strategy for the bottom-up construction of functional protoliving microdevices and provide opportunities for the fabrication of new synthetic cell modules and augmented living/synthetic cell constructs with potential applications in engineered synthetic biology and biotechnology.
    DOI:  https://doi.org/10.1038/s41586-022-05223-w
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