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| Open AccessMicrofluidic vortex focusing for high throughput synthesis of size-tunable liposomes
Liposomes are widely used in pharmaceuticals yet trade-offs between uniform size and mass production, limit production and application. Here, the authors report on the design of a microfluidic vortex focusing microfluidic technique which can mass produce liposomes with controlled size and low variability.
- Jung Yeon Han
- , Joseph N. La Fiandra
- & Don L. DeVoe
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Article
| Open AccessFlash drug release from nanoparticles accumulated in the targeted blood vessels facilitates the tumour treatment
Achieving the delivery of drugs into the centre of solid tumours is a challenge due to the tumour micro-environment. Here, the authors propose a system for using the rapid release of large quantities of drug inside tumour microcapillaries for the gradient-driven diffusion of drugs into solid tumours.
- Ivan V. Zelepukin
- , Olga Yu. Griaznova
- & Andrei V. Zvyagin
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| Open AccessImproved pharmacodynamics of epidermal growth factor via microneedles-based self-powered transcutaneous electrical stimulation
The use of epidermal growth factor for wound healing is limited by transdermal permeability, reduction, and receptor desensitization. Here the authors develop a microneedle-based self-powered transcutaneous electrical stimulation system to overcome these challenges.
- Yuan Yang
- , Ruizeng Luo
- & Zhong Lin Wang
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Article
| Open AccessImpaired mitochondrial oxidative metabolism in skeletal progenitor cells leads to musculoskeletal disintegration
Skeletal progenitors provide a reservoir for bone-forming osteoblasts. However, the major energy source for their osteogenesis remains unresolved. Here, the authors demonstrate that ESCIT-mediated regulation of mitochondrial metabolism is required for osteogenesis.
- Chujiao Lin
- , Qiyuan Yang
- & Jae-Hyuck Shim
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Article
| Open AccessNear infrared-activatable biomimetic nanogels enabling deep tumor drug penetration inhibit orthotopic glioblastoma
Effective drug accumulation in deep glioblastoma multiforme (GBM) lesions remains challenging due to the blood brain barrier. Here, the authors develop a biomimetic nanogel system activated by near infrared irradiation and show high efficacy in orthotopic GBM and GBM stem cells-bearing mouse models.
- Dongya Zhang
- , Sidan Tian
- & Liang Luo
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| Open AccessLigand-switchable nanoparticles resembling viral surface for sequential drug delivery and improved oral insulin therapy
Displaying the correct surface functionality at the right time is important for efficient drug delivery. Here, the authors report on the pH-responsive, sequential presentation of cell-penetrating peptide and liver-targeting moiety designed to improve intestinal absorption and liver targeting and demonstrate this with insulin delivery in vivo.
- Tiantian Yang
- , Aohua Wang
- & Yong Gan
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Article
| Open AccessProgrammable self-regulated molecular buffers for precise sustained drug delivery
Natural buffer molecules ensure the controlled and precise delivery of specific molecules in biology. Here, the authors replicate the natural buffer systems using aptamers with controlled binding efficiency to control and maintain the levels of free drugs both in vitro and in vivo.
- Arnaud Desrosiers
- , Rabeb Mouna Derbali
- & Alexis Vallée-Bélisle
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Article
| Open AccessSmall molecule-assisted assembly of multifunctional ceria nanozymes for synergistic treatment of atherosclerosis
Regulating reactive oxygen species and inflammation are important for treating atherosclerosis. Here, the authors create a cell membrane coated zoledronic acid ceria nanocomposite loaded with probucol for synergistic drug and scavenging nanozyme treatment of atherosclerosis demonstrating application in vivo.
- Xiaoxue Fu
- , Xiaojuan Yu
- & Chao Yu
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Article
| Open AccessOptogenetic-controlled immunotherapeutic designer cells for post-surgical cancer immunotherapy
The induction of long-term systemic immunosurveillance can protect against post-surgery tumor recurrence. Here the authors describe the design of optogenetic-controlled cytokine secreting (IFN-β, TNF-α, and IL-12) engineered mesenchymal stem cells loaded into a hydrogel scaffold, eliciting long-term immune memory and preventing post-operative recurrence in preclinical cancer models.
- Yuanhuan Yu
- , Xin Wu
- & Haifeng Ye
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Article
| Open AccessSuppression of heterotopic ossification in fibrodysplasia ossificans progressiva using AAV gene delivery
Fibrodysplasia ossificans progressiva is an ultra-rare genetic disorder with progressive heterotopic ossification. Yang et al develop different gene therapy approaches and show their efficacy in mouse models and in human induced pluripotent stem cells.
- Yeon-Suk Yang
- , Jung-Min Kim
- & Jae-Hyuck Shim
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Article
| Open AccessHemipiperazines as peptide-derived molecular photoswitches with low-nanomolar cytotoxicity
The development of photochromic systems is an important and growing area of research, in particular for bioactive molecular photoswitches. Here, the authors report on photopharmacological antimitotic agents, operational under visible light, based on a peptide-derived hemipiperazine photochrome.
- Susanne Kirchner
- , Anna-Lena Leistner
- & Zbigniew Pianowski
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Article
| Open AccessMonobody adapter for functional antibody display on nanoparticles for adaptable targeted delivery applications
Targeted nanoparticle delivery to sites of interest is important for targeted therapeutics. Here, the authors improve the targeting efficiency of antibodies on nanoparticles using a monobody adapter to correctly orientate the antibody to preserve targeting function and demonstrate application in targeting the vascular endothelium of human kidneys.
- C. Albert
- , L. Bracaglia
- & G. T. Tietjen
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Article
| Open AccessIn vivo self-assembled siRNA as a modality for combination therapy of ulcerative colitis
Management of ulcerative colitis can require a combination of treatments targeting different pathways. Here the authors design a therapy for ulcerative colitis based on a multitargeted genetic circuit to simultaneously target TNF-α, B7-1 and integrin α4, and show the therapy is effective in male mice with induced or spontaneous genetic colitis.
- Xinyan Zhou
- , Mengchao Yu
- & Xi Chen
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| Open AccessPhotocatalytic glucose depletion and hydrogen generation for diabetic wound healing
Hydrogenation is a treatment for chronic inflammation caused by high glucose levels in diabetic ulcers, However, current therapies have limitations. Here, the authors report on the creation of a visible light photocatalytic agent which depletes glucose in the wound and generates hydrogen to aid in diabetic wound healing.
- Shengqiang Chen
- , Yanxia Zhu
- & Qianjun He
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Article
| Open AccessPayload distribution and capacity of mRNA lipid nanoparticles
Lipid nanoparticles (LNPs) are effective vehicles to deliver mRNA vaccines and therapeutics but assessing the mRNA packaging characteristics in LNPs is challenging. Here, the authors report that mRNA and lipid contents in LNP formulations can be quantitatively examined by multi-laser cylindrical illumination confocal spectroscopy at the single-nanoparticle level.
- Sixuan Li
- , Yizong Hu
- & Hai-Quan Mao
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Article
| Open AccessNeural probe system for behavioral neuropharmacology by bi-directional wireless drug delivery and electrophysiology in socially interacting mice
Technologies for monitoring electrophysiological effects of drugs in behaving animals have limitations. Here the authors report a wireless neural probe system with drug delivery capability for real-time monitoring of drug effects.
- Yousang Yoon
- , Hyogeun Shin
- & Il-Joo Cho
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Article
| Open AccessReconstitution of microtubule into GTP-responsive nanocapsules
GTP-triggered release from drug carriers has huge potential in cancer therapy but current carriers suffers from off target release due to ATP also acting as a trigger. Here, the authors report on the development of a microtubule capsule which is engineered to be responsive to only GTP not ATP and demonstrate targeted drug delivery.
- Noriyuki Uchida
- , Ai Kohata
- & Takuzo Aida
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| Open AccessBacteria loaded with glucose polymer and photosensitive ICG silicon-nanoparticles for glioblastoma photothermal immunotherapy
Different blood-brain barrier permeable systems, such as bacteria loaded with chemotherapy, have been proposed to treat glioblastoma. Here, the authors generate bacteria loaded with glucose polymer and photosensitive ICG silicon-nanoparticles to eliminate bacteria-infected glioblastoma cells and induce an anti-tumour immune response upon photothermal therapy.
- Rong Sun
- , Mingzhu Liu
- & Yao He
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Article
| Open AccessA long-acting formulation of rifabutin is effective for prevention and treatment of Mycobacterium tuberculosis
Non-adherence to anti-tubercular therapy Mycobacterium tuberculosis infection can lead to treatment failure and even the development of drug resistance. In this work, the authors develop a long-acting delivery system of the anti-tuberculosis drug rifabutin and assess translational potential in vivo.
- Manse Kim
- , Claire E. Johnson
- & Martina Kovarova
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| Open AccessReactive oxygen species-responsive and Raman-traceable hydrogel combining photodynamic and immune therapy for postsurgical cancer treatment
Combined immune checkpoint blockade (ICB) and photodynamic therapies have huge potential but suffer from possible damage of the antibodies. Here, the authors create a ROS-responsive hydrogel that protects the ICB antibodies and allows for sustained co-delivery and demonstrate restrained regrowth of tumours in vivo.
- Yiyi Zhang
- , Sidan Tian
- & Liang Luo
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Article
| Open AccessIntrinsically fluorescent polyureas toward conformation-assisted metamorphosis, discoloration and intracellular drug delivery
Biomimetic materials are of interest but can often suffer from limitations caused by the non-native linkages used. Here, the authors report on the creation of amino acid constructed polyureas which can self-assemble into vesicles and nanotubes with aggregation induced fluorescence and the potential for drug delivery applications.
- Yeqiang Zhou
- , Fan Fan
- & Mingming Ding
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Article
| Open AccessMultifunctional synthetic nano-chaperone for peptide folding and intracellular delivery
Molecular chaperones play an important part in protein folding and delivery in nature. Here, the authors report on the creation of a synthetic chaperone to control the folding of therapeutic peptides from random coil to alpha helix and demonstrate enhanced therapeutic potential in an in vivo tumour model.
- Il-Soo Park
- , Seongchan Kim
- & Dal-Hee Min
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Article
| Open AccessDynamic actuation enhances transport and extends therapeutic lifespan in an implantable drug delivery platform
Drug delivery implants suffer from diminished release profiles due to fibrous capsule formation over time. Here, the authors use soft robotic actuation to modulate the immune response of the host to maintain drug delivery over the longer-term and to perform controlled release in vivo.
- William Whyte
- , Debkalpa Goswami
- & Ellen T. Roche
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Article
| Open AccessEngineered bioorthogonal POLY-PROTAC nanoparticles for tumour-specific protein degradation and precise cancer therapy
Proteolysis targeting chimeras (PROTACs) have emerged as promising cancer therapy agents but have suffered from systemic toxicity issues. Here, the authors report on the creation of polymeric PROTAC nanoparticles for tumour targeting delivery and demonstrate protein degradation in vivo, in combination with photodynamic therapy.
- Jing Gao
- , Bo Hou
- & Haijun Yu
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| Open AccessEngineered biomimetic nanoparticles achieve targeted delivery and efficient metabolism-based synergistic therapy against glioblastoma
Targeting cancer-associated metabolism is evolving as a promising approach for cancer therapy. Here, the authors generate cancer cell-membrane encapsulated nanoparticles to induce cell cycle arrest and cytotoxicity in lactate-high cancer cells, reducing tumourigensis in glioblastoma cell-line and patient-derived models.
- Guihong Lu
- , Xiaojun Wang
- & Wei Wei
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Article
| Open AccessPotentiating hypoxic microenvironment for antibiotic activation by photodynamic therapy to combat bacterial biofilm infections
Bacteria in biofilms present unique metabolic conditions that limit the traditional antibiotic treatment. Here, the authors show a photodynamic therapy-activated chemotherapy potentiating the hypoxia of biofilms of methicillin-resistant Staphylococcus aureus, by developing hyaluronic acid nanoparticles functionalized with chlorin e6 and metronidazole.
- Weijun Xiu
- , Ling Wan
- & Lianhui Wang
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Article
| Open AccessMonomethyl auristatin antibody and peptide drug conjugates for trimodal cancer chemo-radio-immunotherapy
Monomethyl auristatin (MMAE), also known for its radiosensitizer properties, is a common antibody drug conjugate used for cancer therapy. Here the authors show that, in combination with radiotherapy, tumor-directed antibodies or peptides conjugated to MMAE promote anti-tumor immune responses, improving response to checkpoint inhibitors in preclinical cancer models.
- Dina V. Hingorani
- , Michael M. Allevato
- & Sunil J. Advani
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| Open AccessAn in situ hydrogel-mediated chemo-immunometabolic cancer therapy
Tryptophan metabolism, leading to the accumulation of kynurenine (Kyn) in the tumor microenvironment, restricts anti-tumor immunity. Here the authors report the design of a hydrogel loaded with doxorubicin and Kyn-degrading kynureninase to relieve immunosuppression, showing anti-tumor responses in preclinical models.
- Bo Wang
- , Jing Chen
- & Minglin Ma
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Article
| Open AccessTPGS-based and S-thanatin functionalized nanorods for overcoming drug resistance in Klebsiella pneumonia
Overproduction of efflux pumps represents an important mechanism of Klebsiella pneumonia resistance to tigecycline. Here, the authors design TPGS- and S-thanatin functionalized nanorods loaded with tigecycline to increase drug accumulation inside bacteria and overcome bacterial resistance.
- Xiaojuan Wang
- , Xiaoling Xu
- & Saiping Jiang
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Article
| Open AccessRu(II) photocages enable precise control over enzyme activity with red light
The cytochrome P450 enzyme CYP1B1 is overexpressed in a variety of tumors, and is correlated with poor treatment outcomes; thus, it is desirable to develop CYP1B1 inhibitors to restore chemotherapy efficacy. Here the authors describe the creation of light-triggered CYP1B1 inhibitors as “prodrugs”, and achieve >6000-fold improvement in potency upon activation with low-energy (660 nm) light.
- Dmytro Havrylyuk
- , Austin C. Hachey
- & Edith C. Glazer
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Article
| Open AccessPeripherally restricted transthyretin-based delivery system for probes and therapeutics avoiding opioid-related side effects
The current peripherally acting mu-opioid receptor antagonists present limited permeability and pharmacokinetic properties. Here, the authors develop a drug delivery approach based on AG10, which demonstrates the impact of mu-opioid receptors in the central nervous system in precipitating opioid-induced constipation.
- Md Tariqul Haque Tuhin
- , Dengpan Liang
- & Mamoun M. Alhamadsheh
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| Open AccessProgrammable probiotics modulate inflammation and gut microbiota for inflammatory bowel disease treatment after effective oral delivery
Inflammatory bowel disease (IBD) is a complex disease that is associated with multiple genetic and environmental variables. Here the authors develop genetically engineered probiotics with selfproducing functional proteins and biofilm self-coating for safe and efficient IBD treatment in mice.
- Jun Zhou
- , Maoyi Li
- & Qian Chen
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| Open AccessTransformation of dolutegravir into an ultra-long-acting parenteral prodrug formulation
Here, using animal models, Deodhar et al. single parenteral dose of dolutegravir (DTG) prodrug nanocrystals sustains drug protein-adjusted 90% inhibitory concentration for up to a year, without injection site reactions or systemic toxicities.
- Suyash Deodhar
- , Brady Sillman
- & Howard E. Gendelman
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| Open AccessEfficient aqueous remote loading of peptides in poly(lactic-co-glycolic acid)
Encapsulation of bioactive peptides in slow-release particles is complex and relies on organic solvents. Here, the authors absorb peptides in a polymer phase from water, creating a simple low-cost encapsulation process in a class of polymer depot.
- Morgan B. Giles
- , Justin K. Y. Hong
- & Steven P. Schwendeman
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| Open AccessReversing insufficient photothermal therapy-induced tumor relapse and metastasis by regulating cancer-associated fibroblasts
Photothermal therapy (PTT) has emerged as a promising approach for cancer treatment. Here, in preclinical cancer models, the authors show that PTT efficacy could be improved using tumor cell-derived microparticles that co-deliver the photosensitizer indocyanine green and a vitamin-D receptor ligand, calcipotriol, resulting in tumor extracellular matrix remodelling and ameliorated anti-tumor immune responses.
- Xin Li
- , Tuying Yong
- & Xiangliang Yang
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| Open AccessMultifunctional metal-organic framework-based nanoreactor for starvation/oxidation improved indoleamine 2,3-dioxygenase-blockade tumor immunotherapy
Inhibited immune response and low levels of delivery inhibit starvation cancer therapies. Here, the authors report on the co-delivery of glucose oxidase and IDO inhibitor 1-methyltryptophan using metal organic frameworks and show amplified release in response to starvation therapy along with immune modulatory effects.
- Liangliang Dai
- , Mengjiao Yao
- & Yanli Zhao
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| Open AccessAn unexpected strategy to alleviate hypoxia limitation of photodynamic therapy by biotinylation of photosensitizers
Type I photodynamic therapy (PDT) sensitizers show good hypoxia tolerance but only few strategies are available for the design of purely organic Type I photosensitizers (PS). Here, the authors use biotinylation as design strategy to obtain PS-Biotin sensitizers with high efficiency for the generation of superoxide anion radicals and singlet oxygen.
- Jing An
- , Shanliang Tang
- & Wen-Heng Zheng
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Article
| Open AccessBioorthogonal in situ assembly of nanomedicines as drug depots for extracellular drug delivery
Delivering the correct concentration of drugs to the correct location is a challenge in cancer therapy. Here, the authors generate a drug loaded nanoparticle that enlarges following contact with the internal tumour cell environment, resulting in the retention of the nanoparticle and loaded drugs in cancer cells.
- Ziyang Cao
- , Dongdong Li
- & Xianzhu Yang
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Article
| Open AccessBoron encapsulated in a liposome can be used for combinational neutron capture therapy
Boron neutron capture therapy is a type of cancer therapy but is associated with insufficient boron delivery and with poor biocompatibility. Here, the authors constructed boronated lipids to generate - boronsome - and show the system can reduce tumour growth.
- Jiyuan Li
- , Qi Sun
- & Zhibo Liu
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Article
| Open AccessDepletion of tumor associated macrophages enhances local and systemic platelet-mediated anti-PD-1 delivery for post-surgery tumor recurrence treatment
Increased density of tumor associated macrophages has been correlated with tumor recurrence following surgery. Here the authors design an alginate-based hydrogel encapsulating anti-PD-1-conjugated platelets and nanoparticles loaded with the macrophage-depleting CSF-1R inhibitor pexidartinib, showing inhibition of post-surgery tumor recurrence in preclinical models.
- Zhaoting Li
- , Yingyue Ding
- & Quanyin Hu
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Article
| Open AccessFibroblast activation protein activated antifibrotic peptide delivery attenuates fibrosis in mouse models of liver fibrosis
Activated hepatic stellate cells contribute towards the pathogenesis of liver fibrosis, and overexpress fibroblast activation protein. Here the authors report a targeted peptide-delivery system in which fibroblast activation protein liberates the antifibrotic peptide melittin, and demonstrate the approach attenuates fibrosis in mouse models of liver fibrosis.
- Jaiwoo Lee
- , Junho Byun
- & Yu-Kyoung Oh
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Article
| Open AccessThermosensitive hydrogel releasing nitric oxide donor and anti-CTLA-4 micelles for anti-tumor immunotherapy
Nitric oxide exerts a multitude of physiological functions and has also been exploited for anticancer therapies. Here the authors report the design of a micelle-releasing thermosensitive hydrogel system for the concomitant locoregional and lymphatic delivery of a nitric oxide donor and an anti-CTLA4 antibody, showing anti-tumor immune responses in preclinical cancer models.
- Jihoon Kim
- , David M. Francis
- & Susan N. Thomas
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Article
| Open AccessMicroalgae-based oral microcarriers for gut microbiota homeostasis and intestinal protection in cancer radiotherapy
Protecting the whole small intestine from radiation-induced intestinal injury during the radiotherapy of abdominal or pelvic solid tumors remains an unmet clinical need. Here the authors use a natural microalga to readily construct an oral delivery system to achieve effective radioprotection for the small intestine.
- Dongxiao Zhang
- , Danni Zhong
- & Min Zhou
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Article
| Open AccessHigh drug-loaded microspheres enabled by controlled in-droplet precipitation promote functional recovery after spinal cord injury
High drug loading improves therapeutic efficacy and reduces side effects in drug delivery. Here, the authors use controlled diffusion of solvents to precipitate drug nanoparticles in polymer particles while the polymer is solidifying and demonstrate the particles for drug delivery in a spinal cord injury model.
- Wei Li
- , Jian Chen
- & Dongfei Liu
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Article
| Open AccessLapcin, a potent dual topoisomerase I/II inhibitor discovered by soil metagenome guided total chemical synthesis
Chemical synthesis of secondary metabolites isolated from nature, and derivatives thereof, is still a paradigm of significance to drug development. Here the authors instead use bioinformatics to analyze a biosynthetic gene cluster found in the soil metagenome, and chemical synthesis of its predict product to produce lapcin, a dual topoisomerase I/II inhibitor with promising activity against cancer cell lines.
- Zongqiang Wang
- , Nicholas Forelli
- & Sean F. Brady
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Article
| Open AccessDegradable mesoporous semimetal antimony nanospheres for near-infrared II multimodal theranostics
The properties of mesoporous nanomaterials have been exploited for several applications, including drug delivery and NIR-II photoacoustic imaging. Here, the authors design monodispersed semimetallic mesoporous antimony nanospheres with photothermal conversion efficiency in the second near-infrared range and drug loading capacity, showing their potential for cancer photothermal/chemo therapy.
- Yu Chen
- , Zhongzheng Yu
- & Junle Qu
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Article
| Open AccessA bioactivated in vivo assembly nanotechnology fabricated NIR probe for small pancreatic tumor intraoperative imaging
Fluorescence probes for detecting tumours during surgery can suffer from poor accumulation and short imaging windows. Here, the author develop fluorescence probes with multiple motifs that permit enhanced circulation times, tumour targeting and use the probes to image pancreatic cancer in mice
- Han Ren
- , Xiang-Zhong Zeng
- & Li-Li Li
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Article
| Open AccessA polytherapy based approach to combat antimicrobial resistance using cubosomes
An increasing prevalence of Gram-negative bacteria increases the interest in nanotherapies to treat antibiotic resistance. Here, the authors examine the antimicrobial activity of polymyxin-loaded cubosomes and explore a polytherapy treatment of pathogens with cubosomes in combination with polymyxin.
- Xiangfeng Lai
- , Mei-Ling Han
- & Hsin-Hui Shen
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Article
| Open AccessBiomimetic nanoparticles deliver mRNAs encoding costimulatory receptors and enhance T cell mediated cancer immunotherapy
Antibodies targeting OX40 or CD137, two T cell costimulatory receptors, have been shown to improve antitumor immunity. Here the authors design a phospholipid-derived nanoparticle to deliver OX40 or CD137 mRNA to T cells in vivo, improving efficacy of anti-OX40 and anti-CD137 antibody therapy in preclinical tumor models.
- Wenqing Li
- , Xinfu Zhang
- & Yizhou Dong