共查询到20条相似文献，搜索用时 15 毫秒
1.
Yan Zou Meng Zheng Weijing Yang Fenghua Meng Kanjiro Miyata Hyun Jin Kim Kazunori Kataoka Zhiyuan Zhong 《Advanced materials (Deerfield Beach, Fla.)》2017,29(42)
Small interfering RNA (siRNA) offers a highly selective and effective pharmaceutical for various life‐threatening diseases, including cancers. The clinical translation of siRNA is, however, challenged by its short plasma life, poor cell uptake, and cumbersome intracellular trafficking. Here, cNGQGEQc peptide‐functionalized reversibly crosslinked chimaeric polymersomes (cNGQ/RCCPs) is shown to mediate high‐efficiency targeted delivery of Polo‐like kinase1 specific siRNA (siPLK1) to orthotopic human lung cancer in nude mice. Strikingly, siRNA is completely and tightly loaded into the aqueous lumen of the polymersomes at an unprecedentedly low N/P ratio of 0.45. cNGQ/RCCPs loaded with firefly luciferase specific siRNA (siGL3) or siPLK1 are efficiently taken up by α3β1‐integrin‐overexpressing A549 lung cancer cells and quickly release the payloads to the cytoplasm, inducing highly potent and sequence‐specific gene silencing in vitro. The in vivo studies using nude mice bearing orthotopic A549 human lung tumors reveal that siPLK1‐loaded cNGQ/RCCPs boost long circulation, superb tumor accumulation and selectivity, effective suppression of tumor growth, and significantly improved survival time. These virus‐mimicking chimaeric polymersomes provide a robust and potent platform for targeted cancer siRNA therapy. 相似文献
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Wenxing Gu Jingnan An Hao Meng Na Yu Yinan Zhong Fenghua Meng Yang Xu Jeroen J. L. M. Cornelissen Zhiyuan Zhong 《Advanced materials (Deerfield Beach, Fla.)》2019,31(46)
Chemotherapy is widely used in the clinic though its benefits are controversial owing to low cancer specificity. Nanovehicles capable of selectively transporting drugs to cancer cells have been energetically pursued to remodel cancer treatment. However, no active targeting nanomedicines have succeeded in clinical translation to date, partly due to either modest targetability or complex fabrication. CD44‐specific A6 short peptide (KPSSPPEE) functionalized polymersomal epirubicin (A6‐PS‐EPI), which boosts targetability and anticancer efficacy toward human multiple myeloma (MM) in vivo, is described. A6‐PS‐EPI encapsulating 11 wt% EPI is small (≈55 nm), robust, reduction‐responsive, and easy to fabricate. Of note, A6 decoration markedly augments the uptake and anticancer activity of PS‐EPI in CD44‐overexpressing LP‐1 MM cells. A6‐PS‐EPI displays remarkable targeting ability to orthotopic LP‐1 MM, causing depleted bone damage and striking survival benefits compared to nontargeted PS‐EPI. Overall, A6‐PS‐EPI, as a simple and intelligent nanotherapeutic, demonstrates high potential for clinical translation. 相似文献
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Masoud Farshbaf Roya Salehi Nasim Annabi Rovshan Khalilov 《Drug development and industrial pharmacy》2018,44(3):452-462
In the current study, we proposed a facile method for fabrication of multifunctional pH- and thermo-sensitive magnetic nanocomposites (MNCs) as a theranostic agent for using in targeted drug delivery and magnetic resonance imaging (MRI). To this end, we decorated Fe3O4 magnetic nanoparticles (MNPs) with N,N-dimethylaminoethyl methacrylate (DMAEMA) and N-isopropylacrylamide (NIPAAm), best known for their pH- and thermo-sensitive properties, respectively. We also conjugated mesoporous silica nanoparticles (MSNs) to polymer matrix acting as drug container to enhance the drug encapsulation efficacy. Methotroxate (MTX) as a model drug was successfully loaded in MNCs (M-MNCs) via surface adsorption onto MSNs and electrostatic interaction between drug and carrier. The pH- and temperature-triggered release of MTX was concluded through the evaluation of in vitro release at both physiological and simulated tumor tissue conditions. Based on in vitro cytotoxicity assay results, M-MNCs significantly revealed higher antitumor activity compared to free MTX. In vitro MR susceptibility experiment showed that M-MNCs relatively possessed high transverse relaxivity (r2) of about 0.15?mM?1·ms?1 and a linear relationship between the transverse relaxation rate (R2) and the Fe concentration in the M-MNCs was also demonstrated. Therefore, the designed MNCs can potentially become smart drug carrier, while they also can be promising MRI negative contrast agent. 相似文献
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Magdiel Inggrid Setyawati Rajaletchumy Veloo Kutty David Tai Leong 《Small (Weinheim an der Bergstrasse, Germany)》2016,12(40):5601-5611
Targeted drug delivery is one of the key challenges in cancer nanomedicine. Stoichiometric and spatial control over the antibodies placement on the nanomedicine vehicle holds a pivotal role to overcome this key challenge. Here, a DNA tetrahedral is designed with available conjugation sites on its vertices, allowing to bind one, two, or three cetuximab antibodies per DNA nanostructure. This stoichiometrically definable cetuximab conjugated DNA nanostructure shows enhanced targeting on the breast cancer cells, which results with higher overall killing efficacy of the cancer cells. 相似文献
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Baoji Du Li Tian Xiaoxiao Gu Dan Li Erkang Wang Jin Wang 《Small (Weinheim an der Bergstrasse, Germany)》2015,11(19):2333-2340
Gene therapy is a potential method for treating a large range of diseases. Gene vectors are widely used in gene therapy for promoting the gene delivery efficiency to the target cells. Here, gold nanoparticles (AuNPs) coated with dimethyldioctadecylammonium bromide (DODAB)/dioleoylphosphatidylethanolamine (DOPE) are synthesized using a facile method for a new gene vector (DODAB/DOPE‐AuNPs), which possess 3‐ and 1.5‐fold higher transfection efficiency than those of DODAB‐AuNPs and a commercial transfection agent, respectively. Meanwhile, it is nontoxic with concentrations required for effective gene delivery. Imaging and quantification studies of cellular uptake reveal that DOPE increases gene copies in cells, which may be attributed to the smaller size of AuNPs/DNA complexes. The dissociation efficiency of DNA from the endocytic pathway is quantified by incubating with different buffers and investigated directly in the cells. The results suggest that DOPE increases the internalization of AuNPs/DNA complexes and promotes DNA release from early endosomes for the vector is sensitive to the anionic lipid membrane and the decreasing pH along the endocytic pathway. The new vector contains the potential to be the new alternative as gene delivery vector for biomedical applications. 相似文献
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Hannah J. Vaughan Jordan J. Green Stephany Y. Tzeng 《Advanced materials (Deerfield Beach, Fla.)》2020,32(13):1901081
Nucleic acids are a promising type of therapeutic for the treatment of a wide range of conditions, including cancer, but they also pose many delivery challenges. For efficient and safe delivery to cancer cells, nucleic acids must generally be packaged into a vehicle, such as a nanoparticle, that will allow them to be taken up by the target cells and then released in the appropriate cellular compartment to function. As with other types of therapeutics, delivery vehicles for nucleic acids must also be designed to avoid unwanted side effects; thus, the ability of such carriers to target their cargo to cancer cells is crucial. Classes of nucleic acids, hurdles that must be overcome for effective intracellular delivery, types of nonviral nanomaterials used as delivery vehicles, and the different strategies that can be employed to target nucleic acid delivery specifically to tumor cells are discussed. Additonally, nanoparticle designs that facilitate multiplexed delivery of combinations of nucleic acids are reviewed. 相似文献
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Nianxi Zhao Jian You Zihua Zeng Chun Li Youli Zu 《Small (Weinheim an der Bergstrasse, Germany)》2013,9(20):3477-3484
Nanotechnology has often been applied in the development of targeted drug‐delivery systems for the treatment of cancer. An ideal nanoscale system for drug delivery should be able to selectively deliver and rapidly release the carried therapeutic drug(s) in cancer cells and, more importantly, not react to off‐target cells so as to eliminate unwanted toxicity on normal tissues. To reach this goal, a selective chemotherapeutic is formulated using a hollow gold nanosphere (HAuNS) equipped with a biomarker‐specific aptamer (Apt), and loaded with the chemotherapy drug doxorubicin (DOX). The formed Apt‐HAuNS‐Dox, approximately 42 nm in diameter, specifically binds to lymphoma tumor cells and does not react to control cells that do not express the biomarker. Through aptamer‐mediated selective cell binding, the Apt‐HAuNS‐Dox is internalized exclusively into the targeted tumor cells, and then released the DOX intracellularly. Of note, although the formed Apt‐HAuNS‐Dox is stable under normal biological conditions (pH 7.4), it appears ultrasensitive to pH change and rapidly releases 80% of the loaded DOX within 2 h at pH 5.0, a condition seen in cell lysosomes. Functional assays using cell mixtures show that the Apt‐HAuNS‐Dox selectively kills lymphoma tumor cells, but has no effect on the growth of the off‐target cells in the same cultures, indicating that this ultra pH‐sensitive Apt‐HAuNS‐Dox can selectively treat cancer through specific aptamer guidance, and will have minimal side effects on normal tissue. 相似文献
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Bo Yu Shreya Goel Dalong Ni Paul A. Ellison Cerise M. Siamof Dawei Jiang Liang Cheng Lei Kang Faquan Yu Zhuang Liu Todd E. Barnhart Qianjun He Han Zhang Weibo Cai 《Advanced materials (Deerfield Beach, Fla.)》2018,30(13)
Nanoengineering of cell membranes holds great potential to revolutionize tumor‐targeted theranostics, owing to their innate biocompatibility and ability to escape from the immune and reticuloendothelial systems. However, tailoring and integrating cell membranes with drug and imaging agents into one versatile nanoparticle are still challenging. Here, multicompartment membrane‐derived liposomes (MCLs) are developed by reassembling cancer cell membranes with Tween‐80, and are used to conjugate 89Zr via deferoxamine chelator and load tetrakis(4‐carboxyphenyl) porphyrin for in vivo noninvasive quantitative tracing by positron emission tomography imaging and photodynamic therapy (PDT), respectively. Radiolabeled constructs, 89Zr‐Df‐MCLs, demonstrate excellent radiochemical stability in vivo, target 4T1 tumors by the enhanced permeability and retention effect, and are retained long‐term for efficient and effective PDT while clearing gradually from the reticuloendothelial system via hepatobiliary excretion. Toxicity evaluation confirms that the MCLs do not impose acute or chronic toxicity in intravenously injected mice. Additionally, 89Zr‐labeled MCLs can execute rapid and highly sensitive lymph node mapping, even for deep‐seated sentinel lymph nodes. The as‐developed cell membrane reassembling route to MCLs could be extended to other cell types, providing a versatile platform for disease theranostics by facilely and efficiently integrating various multifunctional agents. 相似文献
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Jia-Yi Lin Hai-Jun Liu Ye Wu Jin-Mei Jin Yu-Dong Zhou Hong Zhang Dale G. Nagle Hong-Zhuan Chen Wei-Dong Zhang Xin Luan 《Small (Weinheim an der Bergstrasse, Germany)》2023,19(18):2207778
Targeted protein degradation (TPD) is an emerging therapeutic strategy with the potential of targeting undruggable pathogenic proteins. After the first proof-of-concept proteolysis-targeting chimeric (PROTAC) molecule was reported, the TPD field has entered a new era. In addition to PROTAC, numerous novel TPD strategies have emerged to expand the degradation landscape. However, their physicochemical properties and uncontrolled off-target side effects have limited their therapeutic efficacy, raising concerns regarding TPD delivery system. The combination of TPD and nanotechnology offers great promise in improving safety and therapeutic efficacy. This review provides an overview of novel TPD technologies, discusses their clinical applications, and highlights the trends and perspectives in TPD nanomedicine. 相似文献
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Marzia Massignani Caterina LoPresti Adam Blanazs Jeppe Madsen Steven P. Armes Andrew L. Lewis Giuseppe Battaglia 《Small (Weinheim an der Bergstrasse, Germany)》2009,5(21):2424-2432
Cell cytosol and the different subcellular organelles house the most important biochemical processes that control cell functions. Effective delivery of bioactive agents within cells is expected to have an enormous impact on both gene therapy and the future development of new therapeutic and/or diagnostic strategies based on single‐cell–bioactive‐agent interactions. Herein a biomimetic nanovector is reported that is able to enter cells, escape from the complex endocytic pathway, and efficiently deliver actives within clinically relevant cells without perturbing their metabolic activity. This nanovector is based on the pH‐controlled self‐assembly of amphiphilic copolymers into nanometer‐sized vesicles (or polymersomes). The cellular‐uptake kinetics can be regulated by controlling the surface chemistry, the polymersome size, and the polymersome surface topology. The latter is controlled by the extent of polymer–polymer phase separation within the external envelope of the polymersome. 相似文献
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Simon Matoori Yinyin Bao Aaron Schmidt Eric J. Fischer Rafael Ochoa‐Sanchez Mlanie Tremblay Mariana M. Oliveira Christopher F. Rose Jean‐Christophe Leroux 《Small (Weinheim an der Bergstrasse, Germany)》2019,15(50)
Ammonia‐scavenging transmembrane pH‐gradient poly(styrene)‐b‐poly(ethylene oxide) polymersomes are investigated for the oral treatment and diagnosis of hyperammonemia, a condition associated with serious neurologic complications in patients with liver disease as well as in infants with urea cycle disorders. While these polymersomes are highly stable in simulated intestinal fluids at extreme bile salt and osmolality conditions, they unexpectedly do not reduce plasmatic ammonia levels in cirrhotic rats after oral dosing. Incubation in dietary fiber hydrogels mimicking the colonic environment suggests that the vesicles are probably destabilized during the dehydration of the intestinal chyme. The findings question the relevance of commonly used simulated intestinal fluids for studying vesicular stability. With the encapsulation of a pH‐sensitive dye in the polymersome core, the local pH increase upon ammonia influx could be exploited to assess the ammonia concentration in the plasma of healthy and cirrhotic rats as well as in other fluids. Due to its high sensitivity and selectivity, this polymersome‐based assay could prove useful in the monitoring of hyperammonemic patients and in other applications such as drug screening tests. 相似文献
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Xi Yu Xingchun Gou Peng Wu Liang Han Daofeng Tian Fengyi Du Zeming Chen Fuyao Liu Gang Deng Ann T. Chen Chao Ma Jun Liu Sara M. Hashmi Xing Guo Xiaolong Wang Haitian Zhao Xinran Liu Xudong Zhu Kevin Sheth Qianxue Chen Louzhen Fan Jiangbing Zhou 《Advanced materials (Deerfield Beach, Fla.)》2018,30(7)
Clinical translation of therapeutic peptides, particularly those that require penetration of the cell membrane or are cytolytic, is a major challenge. A novel approach based on a complementary mechanism, which has been widely used for guided synthesis of DNA or RNA nanoparticles, for de novo design of activatable protein nanoparticles (APNPs) for targeted delivery of therapeutic peptides is described. APNPs are formed through self‐assembly of three independent polypeptides based on pairwise coiled‐coil dimerization. They are capable of long circulation in the blood and can be engineered to target diseases. Peptides to be delivered are incorporated into APNPs and released into the disease microenvironment by locally enriched proteases. It is demonstrated that APNPs mediate efficient delivery of NR2B9c, a neuroprotective peptide that functions after cell penetration, and melittin, a cytolytic peptide that perturbs the lipid bilayer, for effective treatment of stroke and cancer, respectively. Due to their robust properties, simple design, and economic costs, APNPs have great potential to serve as a versatile platform for controlled delivery of therapeutic peptides. 相似文献
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Dafeng Chu Xinyue Dong Xutong Shi Canyang Zhang Zhenjia Wang 《Advanced materials (Deerfield Beach, Fla.)》2018,30(22)
White blood cells (WBCs) are a major component of immunity in response to pathogen invasion. Neutrophils are the most abundant WBCs in humans, playing a central role in acute inflammation induced by pathogens. Adhesion to vasculature and tissue infiltration of neutrophils are key processes in acute inflammation. Many inflammatory/autoimmune disorders and cancer therapies have been found to be involved in activation and tissue infiltration of neutrophils. A promising strategy to develop novel targeted drug delivery systems is the targeting and exploitation of activated neutrophils. Herein, a new drug delivery platform based on neutrophils is reviewed. There are two types of drug delivery systems: neutrophils as carriers and neutrophil‐membrane‐derived nanovesicles. It is discussed how nanoparticles hijack neutrophils in vivo to deliver therapeutics across blood vessel barriers and how neutrophil‐membrane‐derived nanovesicles target inflamed vasculature. Finally, the potential applications of neutrophil‐based drug delivery systems in treating inflammation and cancers are presented. 相似文献
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Jing Tan Chuanyu Sun Ke Xu Changchun Wang Jia Guo 《Small (Weinheim an der Bergstrasse, Germany)》2015,11(47):6338-6346
5‐Aminolevulinic acid (ALA) is a widely used photodynamic therapy (PDT) prodrug in the clinic. It can be metalized to the photosensitizer PpIX, which produces toxic singlet oxygen to kill cancer cells upon visible light irradiation. Herein, a core/shell‐structured vehicle is designed to comprise magnetite colloidal supraparticles (MCSPs) as cores and ALA‐ZnII coordination polymers as shells (Fe3O4@ALA‐ZnII) for target pro‐photosensitizer delivery. The coordination polymers with 2D layered structures are locally deposited on the MCSPs by the complexation of the ALA and ZnII ions, and are readily controlled by varying the feed precursors and reaction temperatures. The maximum conjugated ALA amount is up to 17%. The Fe3O4@ALA‐ZnII microspheres exhibit pH‐sensitive release of ALA in acidic environment and rapid magnetic responsiveness. Cytotoxicity results demonstrate that Fe3O4@ALA‐ZnII shows a significant inhibitory effect to T24 cells and is nontoxic to 293T normal cells as exposed to the 630 nm visible light for a very short time, which may due to the selective accumulation of ALA‐induced PpIX in T24 cancer cells. Compared to the ALA used alone, the coordination polymer form is more efficient because of the bioactivity of incorporated Zn ions despite underlying the same apoptosis mechanism as ALA agent. 相似文献
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Mohamed A. Yassin Dietmar Appelhans Ralf Wiedemuth Petr Formanek Susanne Boye Albena Lederer Achim Temme Brigitte Voit 《Small (Weinheim an der Bergstrasse, Germany)》2015,11(13):1580-1591
In the context of diligent efforts to improve the tumor targeting efficiency of drug carriers, a shape‐persistent polymersome which possess a pH‐tunable membrane as well as folate targeting antennae is reported. The membrane of such polymersomes behaves as gate which undergoes “on” and “off” switches in response to pH stimuli. Thus, polymersomes can effectively prohibit the premature release of chemotherapeutic agents such as doxorubicin in physiological conditions, but promote drug release once they are triggered in the acidified endosomal compartment. Importantly, the folate moieties are installed on the surface of polymersomes as protruding antennae by doping the polymersomes with folate‐terminated block copolymers designed to have longer PEG segments. Thereby, the folate moieties are freed from concealment and steric effects exerted by the dense PEG corona. The cellular uptake of the FA‐antennae polymersomes by tumor cells is significantly enhanced facilitated by the freely accessible folate antennae; however, the normal cells record a low level of cellular uptake due to the stealth property of the PEG corona. Overall, the excellent biocompatibility, controlled permeability, targeted internalization, as well as selective cytotoxicity of such polymersomes set up the basis for properly smart carrier for targeted drug delivery. 相似文献