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Article
| Open AccessSystemic metastasis-targeted nanotherapeutic reinforces tumor surgical resection and chemotherapy
Failure of conventional clinical therapies such as tumor resection and chemotherapy are mainly due to the ineffective control of tumor metastasis. Here, the authors show that a systemic metastasis-targeted nanotherapeutic may offer a powerful adjunct therapy for suppressing tumor metastasis.
- Minjun Xu
- , Kaili Hu
- & Jun Chen
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Review Article
| Open AccessSex as an important factor in nanomedicine
Given the early failing of therapeutic nanomedicine in the clinic the importance of understanding bio-nano interactions and biosystem parameters has gained much attention. Here, the authors review the work to date that looks at the impact of sex on the applications and outcomes of nanomedicine.
- Mohammah Javad Hajipour
- , Haniyeh Aghaverdi
- & Morteza Mahmoudi
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Article
| Open AccessProgrammably tiling rigidified DNA brick on gold nanoparticle as multi-functional shell for cancer-targeted delivery of siRNAs
Small interfering RNA (siRNA) is used to regulate gene expression for therapeutic purposes, but the design of stable and efficient siRNA delivery systems is challenging. Here, the authors develop a siRNA-encapsulated and aptamer-incorporated core/shell nanoparticle for controlled siRNA delivery, with high stability, tumor-specific targeting and long circulation time.
- Chang Xue
- , Shuyao Hu
- & Zai-Sheng Wu
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Article
| Open AccessPolymer-free corticosteroid dimer implants for controlled and sustained drug delivery
Polymer-based systems are often considered a necessity for controlled drug delivery, but have well-known limitations. Here, the authors report on drug delivery implants formed solely from corticosteroid dimers, which demonstrate controlled release and overcome many of the challenges of polymer-based systems.
- Kyle Battiston
- , Ian Parrag
- & Wendy Naimark
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Article
| Open AccessQuantitative imaging of intracellular nanoparticle exposure enables prediction of nanotherapeutic efficacy
Quantification of intratumoral nanoparticles internalisation in vivo is crucial but challenging. Here, the authors develop a binary ratiometric nanoreporter that can quantify internalisation and predict nanotherapeutic responses based on intracellular nanoparticle exposure.
- Qingqing Yin
- , Anni Pan
- & Yiguang Wang
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Article
| Open Access2D vanadium carbide MXenzyme to alleviate ROS-mediated inflammatory and neurodegenerative diseases
Materials with enzymatic-like activities are of interest for a wide range of applications. Here, the authors report on 2D vanadium carbide MXene nanozymes capable of mimicking multiple enzymes and demonstrate application to treat reactive oxygen species-mediated inflammatory and neurodegenerative diseases.
- Wei Feng
- , Xiuguo Han
- & Yuehua Li
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Article
| Open AccessTargeted apoptosis of macrophages and osteoclasts in arthritic joints is effective against advanced inflammatory arthritis
Celastrol might be useful in treating rheumatoid arthritis in part by inhibiting apoptosis of macrophages; however, systemic toxicity is a concern. Here the authors design celastrol-loaded nanoparticles that release a payload in response to MMP9 cleavage and show these NPs are effective at inducing apoptosis of human macrophages in vitro and a therapeutic effect with an adjuvant-induced arthritis model in rats.
- Caifeng Deng
- , Quan Zhang
- & Zhirong Zhang
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Article
| Open AccessA mussel-inspired film for adhesion to wet buccal tissue and efficient buccal drug delivery
Minimally invasive drug delivery is of wide interest and oral tissue is an attractive target for this. Here, the authors report on the creation of mussel-inspired films for retention on the wet oral tissue for the delivery of drugs by diffusion and transport though the mucosal tissue.
- Shanshan Hu
- , Xibo Pei
- & Jian Wang
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Article
| Open AccessEngineering motile aqueous phase-separated droplets via liposome stabilisation
Bio-mimetic motion has been hard to achieve due to a lack of biocompatible conditions. Here, the authors report the creation of a liposome-stabilised aqueous PEG/dextran Pickering-like emulsion system with motion induced by the Marangoni effect and characterised by negative chemotaxis.
- Shaobin Zhang
- , Claudia Contini
- & Oscar Ces
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Article
| Open AccessTumor-penetrating therapy for β5 integrin-rich pancreas cancer
The iRGD tumor-penetrating peptide can achieve tumor specific drug delivery but whether and how it can penetrate into desmoplastic tumors is unknown. Here, the authors show that β5 integrin expression on tumor cells, mediated by CAFs-derived TGF-β, is required for iRGD penetration into the desmoplastic PDAC microenvironment and that iRGD-based combination therapy is effective in PDAC mouse models.
- Tatiana Hurtado de Mendoza
- , Evangeline S. Mose
- & Kazuki N. Sugahara
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Perspective
| Open AccessDegradable polymeric vehicles for postoperative pain management
Pain management is an extremely important topic both medically and socio-economically. Here the authors offer an overview of the use of degrading polymeric materials for delivery of pharmaceutical agents for pain management and offer a perspective of the future directions of the field.
- Natasha C. Brigham
- , Ru-Rong Ji
- & Matthew L. Becker
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Article
| Open AccessImmunomodulating nano-adaptors potentiate antibody-based cancer immunotherapy
Current strategies to boost anti-tumor immune response include the use of immune checkpoint inhibitors and bispecific T cell-engaging antibodies. Here the authors describe a versatile antibody immobilization nanoplatform that can be used to deliver different combinations of immunotherapeutics, showing therapeutic superiority in pre-clinical models.
- Cheng-Tao Jiang
- , Kai-Ge Chen
- & Jun Wang
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Article
| Open AccessPhotocatalysis-mediated drug-free sustainable cancer therapy using nanocatalyst
Nanoparticles have been used to reduce the toxicity associated with chemotherapeutic agents. Here, the authors report a Z-scheme SnS1.68-WO2.41 nanocatalyst for photocatalytic generation of oxidative holes and hydrogen molecules for drug-free therapeutic strategy.
- Bin Zhao
- , Yingshuai Wang
- & Qianjun He
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Article
| Open AccessSpatiotemporally programmable cascade hybridization of hairpin DNA in polymeric nanoframework for precise siRNA delivery
Controlled delivery of siRNA is important for potential clinical applications. Here, the authors report on the use of cascade hybridization of DNA hairpins with ATP aptamers in DNA crosslinked polymer nanoparticles for triggered release of siRNA and demonstrate anticancer applications.
- Feng Li
- , Wenting Yu
- & Dayong Yang
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Article
| Open Access3D bioprinting of high cell-density heterogeneous tissue models through spheroid fusion within self-healing hydrogels
Cellular models are needed to study disease in vitro and to screen drugs for toxicity and efficacy. Here the authors develop a bioprinting approach to transfer spheroids into self-healing support hydrogels at high resolution, which enables their patterning and fusion into high-cell density microtissues of prescribed spatial organization.
- Andrew C. Daly
- , Matthew D. Davidson
- & Jason A. Burdick
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Article
| Open AccessActivatable polymer nanoagonist for second near-infrared photothermal immunotherapy of cancer
Precise control of immune response remains challenging for cancer immunotherapy. Here, the authors report on photothermally activatable semiconducting polymeric pro-agonist in response to second near-infrared window light for regulated photothermal immunotherapy.
- Yuyan Jiang
- , Jiaguo Huang
- & Kanyi Pu
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Article
| Open AccessTransdermal electroosmotic flow generated by a porous microneedle array patch
Transdermal delivery has emerged as a preferred method of drug delivery. Here, the authors report on the application of porous polymer microneedles coupled with electroosmosis powered by enzymatic batteries for the transport of small and large molecules through the skin.
- Shinya Kusama
- , Kaito Sato
- & Matsuhiko Nishizawa
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Article
| Open AccessSurface chemistry-mediated modulation of adsorbed albumin folding state specifies nanocarrier clearance by distinct macrophage subsets
Polymeric nanocarriers used for drug delivery are often coated by albumin in vivo influencing the therapeutic outcomes. Here, the authors engineer the surface chemistry of a nanocarrier to either stabilize or denature the structure of adsorbed albumin, resulting in evasion or clearance by macrophages.
- Michael P. Vincent
- , Sharan Bobbala
- & Evan A. Scott
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Article
| Open AccessBoosting anti-PD-1 therapy with metformin-loaded macrophage-derived microparticles
Durable response rate to anti-PD-1/PD-L1 therapy remains relatively low in patients with cancer. Here the authors show that metformin-loaded mannose-modified macrophage-derived microparticles reprogram the tumor immune microenvironment and improve responses to anti-PD-1 therapy.
- Zhaohan Wei
- , Xiaoqiong Zhang
- & Xiangliang Yang
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Review Article
| Open AccessResilin-mimetics as a smart biomaterial platform for biomedical applications
Advances made in synthesis and analytical techniques has allowed the exploration and mimicry of natural materials. Resilin-mimetics have emerged from this advance as a biomaterial with a range of potential applications. Here, the authors review the history and current research on resilin-mimetics, providing a future perspective.
- Rajkamal Balu
- , Naba K. Dutta
- & Namita Roy Choudhury
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Article
| Open AccessImprovement of obesity-associated disorders by a small-molecule drug targeting mitochondria of adipose tissue macrophages
Adipose tissue macrophages are central to controlling inflammation in the context of obesity. Here the authors present a new infrared dye (IR-61) that accumulates in the mitochondria of these cells resulting in anti-inflammatory effects that counter obesity-associated pathology in mice.
- Yawei Wang
- , Binlin Tang
- & Chunmeng Shi
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Article
| Open AccessTumor microenvironment-targeted nanoparticles loaded with bortezomib and ROCK inhibitor improve efficacy in multiple myeloma
The tumour microenvironment (TME) has a major role in chemoresistance in multiple myeloma. The authors show that a nanoparticle targeted to TME and loaded with bortezomib (BTZ) and Y27632 is more effective than free drugs, non-targeted and single-agent controls and reduces BTZ-related side effects.
- Cinzia Federico
- , Kinan Alhallak
- & Abdel Kareem Azab
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Article
| Open AccessCRISPR based editing of SIV proviral DNA in ART treated non-human primates
Removal of integrated HIV DNA remains a roadblock for HIV cure. Here, Mancuso et al. show that intravenous administration of an adeno-associated virus-based CRISPR/Cas9 gene editing construct to SIV-infected macaques results in excision of integrated proviral DNA from infected blood cells and tissues known to be viral reservoirs.
- Pietro Mancuso
- , Chen Chen
- & Kamel Khalili
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Article
| Open AccessSystemic brain tumor delivery of synthetic protein nanoparticles for glioblastoma therapy
The lack of effective drug delivery strategies has impaired the therapeutic progress in the treatment of glioblastoma (GBM). Here, the authors engineer synthetic protein nanoparticle based on polymerized human serum albumin equipped with the cell-penetrating peptide iRGD to deliver siRNA against STAT3 and report improved survival in a mouse model of GBM.
- Jason V. Gregory
- , Padma Kadiyala
- & Joerg Lahann
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Article
| Open AccessCo-administered antibody improves penetration of antibody–dye conjugate into human cancers with implications for antibody–drug conjugates
Antibody-drug conjugates targeting high expression receptors can suffer from poor tumour penetration. Here, the authors use unconjugated antibody to improve the penetration of an antibody-dye conjugate in a clinical study, supporting further clinical investigation of the co-administration strategy.
- Guolan Lu
- , Naoki Nishio
- & Eben L. Rosenthal
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Review Article
| Open AccessEngineering microrobots for targeted cancer therapies from a medical perspective
Microbot delivery devices are the latest development in attempts to overcome the systemic toxicity associated with classical chemotherapy. Here, the authors review the recent progress in the field with a focus on the clinical translation and potential of the research and give a future perspective on this topic.
- Christine K. Schmidt
- , Mariana Medina-Sánchez
- & Oliver G. Schmidt
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Article
| Open AccessA universal dual mechanism immunotherapy for the treatment of influenza virus infections
In this study, the authors combine an anti-viral drug and immune system inducer to treat influenza A and B viral infections in vitro and in vivo. They show that the compound outperforms zanamivir alone as it is still able to clear infection three days post infection, and it can be administered via different routes without reduced efficacy.
- Xin Liu
- , Boning Zhang
- & Philip S. Low
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Article
| Open AccessTwo-tier supramolecular encapsulation of small molecules in a protein cage
Protein cages are used for encapsulation of macromolecules such as proteins and nucleic acids. Here, the authors report a strategy to encapsulate poorly soluble small molecules within porous protein cages through capsid-templated micelle formation and show that the resulting lipoprotein-like cages enhance the cellular delivery of these molecules.
- Thomas G. W. Edwardson
- , Stephan Tetter
- & Donald Hilvert
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Article
| Open AccessResensitizing carbapenem- and colistin-resistant bacteria to antibiotics using auranofin
Multi-drug resistant pathogens remain a serious public health threat. Here, Sun and colleagues identify a role for auranofin, which is normally used as a drug for rheumatoid arthritis, for reversing antibiotic resistance to carbapenem and colistin.
- Hongzhe Sun
- , Qi Zhang
- & Hongyan Li
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Article
| Open AccessCombinatorial entropy behaviour leads to range selective binding in ligand-receptor interactions
Multivalent ligand-receptor interactions enhance binding selectivity in biological systems, and may be exploited to design synthetic systems. Here the authors demonstrate a multivalent behavior where the ability to bind the target occurs when the receptor density is within a specific range.
- Meng Liu
- , Azzurra Apriceno
- & Stefano Angioletti-Uberti
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Article
| Open AccessPharmacophore hybridisation and nanoscale assembly to discover self-delivering lysosomotropic new-chemical entities for cancer therapy
Integration of the unique advantages of the fields of drug discovery and drug delivery is invaluable for the advancement of drug development. Here, the authors generate single-drug nanoparticles by hybridising lysomotropic detergents and the bisaminoquinoline-based autophagy inhibitor, and show their therapeutic potential as autophagy-inhibition based combination therapy.
- Zhao Ma
- , Jin Li
- & Yuanpei Li
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Article
| Open AccessMicroenvironment-responsive immunoregulatory electrospun fibers for promoting nerve function recovery
Inflammatory responses determine the pathological course of spinal cord injury. Here, the authors report on pH responsive fibers for triggered release of IL-4 plasmid liposomes and sustained release of nerve growth factor to regulate the immune response and promote nerve regeneration to enhance functional recovery.
- Kun Xi
- , Yong Gu
- & Liang Chen
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Article
| Open AccessSequential drug release via chemical diffusion and physical barriers enabled by hollow multishelled structures
Hollow multishell structures (HoMSs) consist of multiple shells with voids between them that provide separate reaction environments within the same assembly. Here, the authors used TiO2-HoMS to deliver a broad-spectrum antibacterial agent, in three-stages and in response to environmental changes.
- Decai Zhao
- , Nailiang Yang
- & Dan Wang
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Review Article
| Open AccessAdvances and challenges in retinoid delivery systems in regenerative and therapeutic medicine
Retinoids are involved in a wide range of cellular functions; as such, delivery systems for retinoids are of significant clinical interest. Here the authors review the advances in preclinical and clinical testing regarding retinoid formulations in the context of regenerative medicine, brain, cancer, skin and immune diseases.
- Raquel Ferreira
- , Joseph Napoli
- & Lino Ferreira
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Article
| Open AccessUse of ratiometrically designed nanocarrier targeting CDK4/6 and autophagy pathways for effective pancreatic cancer treatment
Aberrant cell cycle machinery and loss of the CDKN2A tumor suppressor locus make CDK4/6 a potential target in pancreatic ductal adenocarcinoma (PDAC). Here, the authors use ratiometrically designed nanoparticles to codeliver the CDK4/6 inhibitor palbociclib and the autophagy inhibitor hydroxychloroquine, and show their synergistic therapeutic effects in mouse model of PDAC.
- Ying Ji
- , Xiangsheng Liu
- & Huan Meng
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Article
| Open AccessLight-triggered switching of liposome surface charge directs delivery of membrane impermeable payloads in vivo
Surface charge plays an important role in determining nanoparticle fate in vivo. Here the authors report on the development of a light triggered charge switching liposome and demonstrate light triggered liposome targeting, uptake and payload delivery in a zebrafish model.
- Gabriela Arias-Alpizar
- , Li Kong
- & Frederick Campbell
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Article
| Open AccessSystemic nanoparticle delivery of CRISPR-Cas9 ribonucleoproteins for effective tissue specific genome editing
Therapeutic targets of CRISPR-Cas can often not be accessed due to lack of carriers to deliver RNPs systematically. Here, the authors engineer modified lipid nanoparticles for delivery of gene editing proteins to specific tissues.
- Tuo Wei
- , Qiang Cheng
- & Daniel J. Siegwart
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Article
| Open AccessBlood circulation of soft nanomaterials is governed by dynamic remodeling of protein opsonins at nano-biointerface
The blood circulation time is important to the biomedical application of nanomaterials. Here, the authors explore the effect of protein corona formation on the blood residency of nanomaterials and show circulation times are governed by the dynamic remodelling of protein opsonins in vivo.
- Srinivas Abbina
- , Lily E. Takeuchi
- & Jayachandran N. Kizhakkedathu
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Article
| Open AccessSynergistic lipid compositions for albumin receptor mediated delivery of mRNA to the liver
Lipid-like nanoparticles have applications as non-viral delivery systems for mRNA. Here, the authors develop biodegradable lipids with improved clearance and reduced toxicity.
- Lei Miao
- , Jiaqi Lin
- & Daniel G. Anderson
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Article
| Open AccessLight-triggered release of conventional local anesthetics from a macromolecular prodrug for on-demand local anesthesia
Local anesthetic sustained release systems suffer from untriggered rapid drug release upon application. Here the authors overcome this issue by covalently linking tetracaine to a polymer gel via a photo-cleavable linkage, enabling light-triggered and repeatable drug release.
- Wei Zhang
- , Tianjiao Ji
- & Daniel S. Kohane
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Article
| Open AccessIn situ supramolecular polymerization-enhanced self-assembly of polymer vesicles for highly efficient photothermal therapy
Photothermal therapy (PTT) has recently emerged as a promising approach for cancer therapy. Here, the authors report a hyperbranched polymer vesicle with favorable photothermal stability and high photothermal efficiency for PTT through a supramolecular polymerization-enhanced self-assembly strategy.
- Yannan Liu
- , Hao Wang
- & Yongfeng Zhou
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Article
| Open AccessRegulating vesicle bilayer permeability and selectivity via stimuli-triggered polymersome-to-PICsome transition
Polyion complex vesicles have advantageous applications but have poorly tuneable permeability and nanostructure stability. Here, the authors develop polyion complex vesicles created using a stimuli-triggered transition from polymersomes and show high stability and switchable bilayer permaselectivity.
- Xiaorui Wang
- , Chenzhi Yao
- & Shiyong Liu
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Article
| Open AccessBisphosphonate nanoclay edge-site interactions facilitate hydrogel self-assembly and sustained growth factor localization
Nanoclays have been used in composites and for drug delivery but have suffered from a trade-off in properties when used for both. Here the authors report on the use of bisphosphonate interactions with nanoclay edges to made drug loaded composites without compromising materials properties or drug loading.
- Yang-Hee Kim
- , Xia Yang
- & Jonathan I. Dawson
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Article
| Open AccessExtracellular nanovesicles for packaging of CRISPR-Cas9 protein and sgRNA to induce therapeutic exon skipping
Expression of Cas9 and gRNA from viral vectors in vivo may cause off-target activity. Here the authors present NanoMEDIC, which uses nanovesicles to transiently deliver editing machinery to hard-to-transfect cells.
- Peter Gee
- , Mandy S. Y. Lung
- & Akitsu Hotta
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Article
| Open AccessMelittin-lipid nanoparticles target to lymph nodes and elicit a systemic anti-tumor immune response
The bee venom melittin has anti-tumor properties but is unsuitable for therapeutic use on its own. Here, the authors generate melittin-nanoparticles and demonstrate that the nanoparticles reduce tumor growth and generate an anti-tumor immune response.
- Xiang Yu
- , Yanfeng Dai
- & Zhihong Zhang
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Article
| Open AccessChemotaxis-driven delivery of nano-pathogenoids for complete eradication of tumors post-phototherapy
The presence of several biological barriers impede the efficacy of nano-mediated drug delivery for solid cancer therapy. Here, the authors develop a nano-pathogenoid system that targets circulating neutrophils and show that it overcomes these biological barriers and improves tumour targeting and efficacy.
- Min Li
- , Shuya Li
- & Yucai Wang
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Article
| Open AccessSustained treatment of retinal vascular diseases with self-aggregating sunitinib microparticles
Neovascular age-related macular degeneration and diabetic retinopathy are currently treated with repeated intravitreous injections of VEGF neutralizing proteins. Here the authors develop a microparticle-loaded tyrosine kinase inhibitor therapy, which is effective for six months after a single injection in preclinical models.
- Hiroki Tsujinaka
- , Jie Fu
- & Peter A. Campochiaro
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Article
| Open AccessBlood-triggered generation of platinum nanoparticle functions as an anti-cancer agent
Platinum based drugs like cisplatin are common chemotherapy treatments for cancer. Here, the authors report on the in situ formation of platinum nanoparticles in patients and demonstrated how platinum nanoparticles can be synthesized using patients’ blood and provide effective drug delivery and cancer treatments.
- Xin Zeng
- , Jie Sun
- & Gen Zhang
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Article
| Open AccessBiointerfacial self-assembly generates lipid membrane coated bacteria for enhanced oral delivery and treatment
Oral microbiota delivery is an approach to treat and prevent disease but suffers from low retention and bioavailability. Here the authors report on a lipid coating to protect against environmental assault maintaining viability and bioactivity of the bacteria and demonstrate effective application in a colitis model.
- Zhenping Cao
- , Xinyue Wang
- & Jinyao Liu