共查询到20条相似文献,搜索用时 46 毫秒
1.
Jinhwan Kim Changshin Jo Won‐Gwang Lim Sungjin Jung Yeong Mi Lee Jun Lim Haeshin Lee Jinwoo Lee Won Jong Kim 《Advanced materials (Deerfield Beach, Fla.)》2018,30(29)
Tumors are 3D, composed of cellular agglomerations and blood vessels. Therapies involving nanoparticles utilize specific accumulations due to the leaky vascular structures. However, systemically injected nanoparticles are mostly uptaken by cells located on the surfaces of cancer tissues, lacking deep penetration into the core cancer regions. Herein, an unprecedented strategy, described as injecting “nanoparticle‐loaded nanoparticles” to address the long‐lasting problem is reported for effective surface‐to‐core drug delivery in entire 3D tumors. The “nanoparticle‐loaded nanoparticle” is a silica nanoparticle (≈150 nm) with well‐developed, interconnected channels (diameter of ≈30 nm), in which small gold nanoparticles (AuNPs) (≈15 nm) with programmable DNA are located. The nanoparticle (AuNPs)‐loaded nanoparticles (silica): (1) can accumulate in tumors through leaky vascular structures by protecting the inner therapeutic AuNPs during blood circulation, and then (2) allow diffusion of the AuNPs for penetration into the entire surface‐to‐core tumor tissues, and finally (3) release a drug triggered by cancer‐characteristic pH gradients. The hierarchical “nanoparticle‐loaded nanoparticle” can be a rational design for cancer therapies because the outer large nanoparticles are effective in blood circulation and in protection of the therapeutic nanoparticles inside, allowing the loaded small nanoparticles to penetrate deeply into 3D tumors with anticancer drugs. 相似文献
2.
The extensive use of gold nanoparticles (AuNPs) in nanomedicine, especially for intracellular imaging, photothermal therapy, and drug delivery, has necessitated the study of how functionalized AuNPs engage with living biological interfaces like the mammalian cell. Nanoparticle size, shape, surface charge, and surface functionality can affect the accumulation of functionalized AuNPs in cells. Confocal microscopy, flow cytometry, and inductively coupled plasma mass spectrometry demonstrate that CaSki cells, a human cervical cancer cell line, internalize AuNPs functionalized with hairpin, single stranded, and double stranded DNA differently. Surface charge and DNA conformation are shown to have no effect on the cell‐nanoparticle interaction. CaSki cells accumulate small DNA‐AuNPs in greater quantities than large DNA‐AuNPs, demonstrating that size is the major contributor to cellular uptake properties. These data suggest that DNA‐AuNPs can be easily tailored through modulation of size to design functional AuNPs with optimal cellular uptake properties and enhanced performance in nanomedicine applications. 相似文献
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Wen‐Jing Song Jin‐Zhi Du Tian‐Meng Sun Pei‐Zhuo Zhang Jun Wang 《Small (Weinheim an der Bergstrasse, Germany)》2010,6(2):239-246
An efficient and safe delivery system for small interfering RNA (siRNA) is required for clinical application of RNA interfering therapeutics. Polyethyleneimine (PEI)‐capped gold nanoparticles (AuNPs) are successfully manufactured using PEI as the reductant and stabilizer, which bind siRNA at an appropriate weight ratio by electrostatic interaction and result in well‐dispersed nanoparticles with uniform structure and narrow size distribution. With siRNA binding, PEI‐capped AuNPs induce more significant and enhanced reduction in targeted green fluorescent protein expression in MDA‐MB‐435s cells, though more internalized PEI/siRNA complexes in cells are evidenced by confocal laser scanning microscopy observation and fluorescence‐activated cell sorting analyses. PEI‐capped AuNPs/siRNA targeting endogenous cell‐cycle kinase, an oncogene polo‐like kinase 1 (PLK1), display significant gene expression knockdown and induce enhanced cell apoptosis, whereas it is not obvious when the cells are treated with PLK1 siRNA using PEI as the carrier. Without exhibiting cellular toxicity, PEI‐capped AuNPs appear to be suitable as a potential carrier for intracellular siRNA delivery. 相似文献
5.
Continuous Production of Discrete Plasmid DNA‐Polycation Nanoparticles Using Flash Nanocomplexation
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Jose Luis Santos Yong Ren John Vandermark Maani M. Archang John‐Michael Williford Heng‐Wen Liu Jason Lee Tza‐Huei Wang Hai‐Quan Mao 《Small (Weinheim an der Bergstrasse, Germany)》2016,12(45):6214-6222
Despite successful demonstration of linear polyethyleneimine (lPEI) as an effective carrier for a wide range of gene medicine, including DNA plasmids, small interfering RNAs, mRNAs, etc., and continuous improvement of the physical properties and biological performance of the polyelectrolyte complex nanoparticles prepared from lPEI and nucleic acids, there still exist major challenges to produce these nanocomplexes in a scalable manner, particularly for lPEI/DNA nanoparticles. This has significantly hindered the progress toward clinical translation of these nanoparticle‐based gene medicine. Here the authors report a flash nanocomplexation (FNC) method that achieves continuous production of lPEI/plasmid DNA nanoparticles with narrow size distribution using a confined impinging jet device. The method involves the complex coacervation of negatively charged DNA plasmid and positive charged lPEI under rapid, highly dynamic, and homogeneous mixing conditions, producing polyelectrolyte complex nanoparticles with narrow distribution of particle size and shape. The average number of plasmid DNA packaged per nanoparticles and its distribution are similar between the FNC method and the small‐scale batch mixing method. In addition, the nanoparticles prepared by these two methods exhibit similar cell transfection efficiency. These results confirm that FNC is an effective and scalable method that can produce well‐controlled lPEI/plasmid DNA nanoparticles. 相似文献
6.
pH‐Responsive Isoniazid‐Loaded Nanoparticles Markedly Improve Tuberculosis Treatment in Mice
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Angela A. Hwang Bai‐Yu Lee Daniel L. Clemens Barbara Jane Dillon Jeffrey I. Zink Marcus A. Horwitz 《Small (Weinheim an der Bergstrasse, Germany)》2015,11(38):5066-5078
Tuberculosis is a major global health problem for which improved therapeutics are needed to shorten the course of treatment and combat emergence of drug resistance. Mycobacterium tuberculosis, the etiologic agent of tuberculosis, is an intracellular pathogen of mononuclear phagocytes. As such, it is an ideal pathogen for nanotherapeutics because macrophages avidly ingest nanoparticles even without specific targeting molecules. Hence, a nanoparticle drug delivery system has the potential to target and deliver high concentrations of drug directly into M. tuberculosis‐infected cells—greatly enhancing efficacy while avoiding off‐target toxicities. Stimulus‐responsive mesoporous silica nanoparticles of two different sizes, 100 and 50 nm, are developed as carriers for the major anti‐tuberculosis drug isoniazid in a prodrug configuration. The drug is captured by the aldehyde‐functionalized nanoparticle via hydrazone bond formation and coated with poly(ethylene imine)–poly(ethylene glycol) (PEI–PEG). The drug is released from the nanoparticles in response to acidic pH at levels that naturally occur within acidified endolysosomes. It is demonstrated that isoniazid‐loaded PEI–PEG‐coated nanoparticles are avidly ingested by M. tuberculosis‐infected human macrophages and kill the intracellular bacteria in a dose‐dependent manner. It is further demonstrated in a mouse model of pulmonary tuberculosis that the nanoparticles are well tolerated and much more efficacious than an equivalent amount of free drug. 相似文献
7.
Local Effects on Airway Inflammation and Systemic Uptake of 5 nm PEGylated and Citrated Gold Nanoparticles in Asthmatic Mice
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Albert J. Omlor Duc D. Le Janine Schlicker Matthias Hannig Raphael Ewen Sebastian Heck Christian Herr Annette Kraegeloh Christina Hein Ralf Kautenburger Guido Kickelbick Robert Bals Juliane Nguyen Q. Thai Dinh 《Small (Weinheim an der Bergstrasse, Germany)》2017,13(10)
Nanotechnology is showing promise in many medical applications such as drug delivery and hyperthermia. Nanoparticles administered to the respiratory tract cause local reactions and cross the blood–air barrier, thereby providing a means for easy systemic administration but also a potential source of toxicity. Little is known about how these effects are influenced by preexisting airway diseases such as asthma. Here, BALB/c mice are treated according to the ovalbumin (OVA) asthma protocol to promote allergic airway inflammation. Dispersions of polyethylene‐glycol‐coated (PEGylated) and citrate/tannic‐acid‐coated (citrated) 5 nm gold nanoparticles are applied intranasally to asthma and control groups, and (i) airway resistance and (ii) local tissue effects are measured as primary endpoints. Further, nanoparticle uptake into extrapulmonary organs is quantified by inductively coupled plasma mass spectrometry. The asthmatic precondition increases nanoparticle uptake. Moreover, systemic uptake is higher for PEGylated gold nanoparticles compared to citrated nanoparticles. Nanoparticles inhibit both inflammatory infiltrates and airway hyperreactivity, especially citrated gold nanoparticles. Although the antiinflammatory effects of gold nanoparticles might be of therapeutic benefit, systemic uptake and consequent adverse effects must be considered when designing and testing nanoparticle‐based asthma therapies. 相似文献
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Spray‐Dried Nanoparticle‐in‐Microparticle Delivery Systems (NiMDS) for Gene Delivery,Comprising Polyethylenimine (PEI)‐Based Nanoparticles in a Poly(Vinyl Alcohol) Matrix
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Jan Schulze Stephanie Kuhn Stephan Hendrikx Michaela Schulz‐Siegmund Tobias Polte Achim Aigner 《Small (Weinheim an der Bergstrasse, Germany)》2018,14(12)
Nucleic acid‐based therapies rely on efficient formulations for nucleic acid protection and delivery. As nonviral strategies, polymeric and lipid‐based nanoparticles have been introduced; however, biological efficacy and biocompatibility as well as poor storage properties due to colloidal instability and their unavailability as ready‐to‐use systems are still major issues. Polyethylenimine is the most widely explored and promising candidate for gene delivery. Polyethylenimine‐based polyplexes and their combination with liposomes, lipopolyplexes, are efficient for DNA or siRNA delivery in vitro and in vivo. In this study, a highly potent spray‐dried nanoparticle‐in‐microparticle delivery system is presented for the encapsulation of polyethylenimine‐based polyplexes and lipopolyplexes into poly(vinyl alcohol) microparticles, without requiring additional stabilizing agents. This easy‐to‐handle gene delivery device allows prolonged nanoparticle storage and protection at ambient temperature. Biological analyses reveal further advantages regarding profoundly reduced cytotoxicity and enhanced transfection efficacies of polyethylenimine‐based nanoparticles from the nanoparticle‐in‐microparticle delivery system over their freshly prepared counterparts, as determined in various cell lines. Importantly, this nanoparticle‐in‐microparticle delivery system is demonstrated as ready‐to‐use dry powder to be an efficient device for the inhalative delivery of polyethylenimine‐based lipopolyplexes in vivo, as shown by transgene expression in mice after only one administration. 相似文献
9.
Effective Gene Delivery into Human Stem Cells with a Cell‐Targeting Peptide‐Modified Bioreducible Polymer
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Jagadish Beloor Suresh Ramakrishna Kihoon Nam Chang Seon Choi Jongkil Kim Sung Hwa Kim Hyong Jin Cho HeungSoo Shin Hyongbum Kim Sung Wan Kim Sang‐Kyung Lee Priti Kumar 《Small (Weinheim an der Bergstrasse, Germany)》2015,11(17):2069-2079
Stem cells are poorly permissive to non‐viral gene transfection reagents. In this study, we explored the possibility of improving gene delivery into human embryonic (hESC) and mesenchymal (hMSC) stem cells by synergizing the activity of a cell‐binding ligand with a polymer that releases nucleic acids in a cytoplasm‐responsive manner. A 29 amino acid long peptide, RVG, targeting the nicotinic acetylcholine receptor (nAchR) was identified to bind both hMSC and H9‐derived hESC. Conjugating RVG to a redox‐sensitive biodegradable dendrimer‐type arginine‐grafted polymer (PAM‐ABP) enabled nanoparticle formation with plasmid DNA without altering the environment‐sensitive DNA release property and favorable toxicity profile of the parent polymer. Importantly, RVG‐PAM‐ABP quantitatively enhanced transfection into both hMSC and hESC compared to commercial transfection reagents like Lipofectamine 2000 and Fugene. ~60% and 50% of hMSC and hESC were respectively transfected, and at increased levels on a per cell basis, without affecting pluripotency marker expression. RVG‐PAM‐ABP is thus a novel bioreducible, biocompatible, non‐toxic, synthetic gene delivery system for nAchR‐expressing stem cells. Our data also demonstrates that a cell‐binding ligand like RVG can cooperate with a gene delivery system like PAM‐ABP to enable transfection of poorly‐permissive cells. 相似文献
10.
Min Hui Averil Chen Jacqueline Lessig Björn Neu Subbu S. Venkatraman Tina T. Wong 《Small (Weinheim an der Bergstrasse, Germany)》2014,10(9):1790-1798
Efficient and safe delivery systems for siRNA therapeutics remain a challenge. Elevated secreted protein, acidic, and rich in cysteine (SPARC) protein expression is associated with tissue scarring and fibrosis. Here we investigate the feasibility of encapsulating SPARC‐siRNA in the bilayers of layer‐by‐layer (LbL) nanoparticles (NPs) with poly(L‐arginine) (ARG) and dextran (DXS) as polyelectrolytes. Cellular binding and uptake of LbL NPs as well as siRNA delivery were studied in FibroGRO cells. siGLO‐siRNA and SPARC‐siRNA were efficiently coated onto hydroxyapatite nanoparticles. The multilayered NPs were characterized with regard to particle size, zeta potential and surface morphology using dynamic light scattering and transmission electron microscopy. The SPARC‐gene silencing and mRNA levels were analyzed using ChemiDOC western blot technique and RT‐PCR. The multilayer SPARC‐siRNA incorporated nanoparticles are about 200 nm in diameter and are efficiently internalized into FibroGRO cells. Their intracellular fate was also followed by tagging with suitable reporter siRNA as well as with lysotracker dye; confocal microscopy clearly indicates endosomal escape of the particles. Significant (60%) SPARC‐gene knock down was achieved by using 0.4 pmole siRNA/μg of LbL NPs in FibroGRO cells and the relative expression of SPARC mRNA reduced significantly (60%) against untreated cells. The cytotoxicity as evaluated by xCelligence real‐time cell proliferation and MTT cell assay, indicated that the SPARC‐siRNA‐loaded LbL NPs are non‐toxic. In conclusion, the LbL NP system described provides a promising, safe and efficient delivery platform as a non‐viral vector for siRNA delivery that uses biopolymers to enhance the gene knock down efficiency for the development of siRNA therapeutics. 相似文献
11.
Vivian Juang Chih‐Hsien Chang Chen‐Shen Wang Hsin‐Ell Wang Yu‐Li Lo 《Small (Weinheim an der Bergstrasse, Germany)》2019,15(49)
Irinotecan is one of the main chemotherapeutic agents for colorectal cancer (CRC). MicroRNA‐200 (miR‐200) has been reported to inhibit metastasis in cancer cells. Herein, pH‐sensitive and peptide‐modified liposomes and solid lipid nanoparticles (SLN) are designed for encapsulation of irinotecan and miR‐200, respectively. These peptides include one cell‐penetrating peptide, one ligand targeted to tumor neovasculature undergoing angiogenesis, and one mitochondria‐targeting peptide. The peptide‐modified nanoparticles are further coated with a pH‐sensitive PEG‐lipid derivative with an imine bond. These specially‐designed nanoparticles exhibit pH‐responsive release, internalization, and intracellular distribution in acidic pH of colon cancer HCT116 cells. These nanoparticles display low toxicity to blood and noncancerous intestinal cells. Delivery of miR‐200 by SLN further increases the cytotoxicity of irinotecan‐loaded liposomes against CRC cells by triggering apoptosis and suppressing RAS/β‐catenin/ZEB/multiple drug resistance (MDR) pathways. Using CRC‐bearing mice, the in vivo results further indicate that irinotecan and miR‐200 in pH‐responsive targeting nanoparticles exhibit positive therapeutic outcomes by inhibiting colorectal tumor growth and reducing systemic toxicity. Overall, successful delivery of miR and chemotherapy by multifunctional nanoparticles may modulate β‐catenin/MDR/apoptosis/metastasis signaling pathways and induce programmed cancer cell death. Thus, these pH‐responsive targeting nanoparticles may provide a potential regimen for effective treatment of colorectal cancer. 相似文献
12.
Bioinspired Diselenide‐Bridged Mesoporous Silica Nanoparticles for Dual‐Responsive Protein Delivery
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Dan Shao Mingqiang Li Zheng Wang Xiao Zheng Yeh‐Hsing Lao Zhimin Chang Fan Zhang Mengmeng Lu Juan Yue Hanze Hu Huize Yan Li Chen Wen‐fei Dong Kam W. Leong 《Advanced materials (Deerfield Beach, Fla.)》2018,30(29)
Controlled delivery of protein therapeutics remains a challenge. Here, the inclusion of diselenide‐bond‐containing organosilica moieties into the framework of silica to fabricate biodegradable mesoporous silica nanoparticles (MSNs) with oxidative and redox dual‐responsiveness is reported. These diselenide‐bridged MSNs can encapsulate cytotoxic RNase A into the 8–10 nm internal pores via electrostatic interaction and release the payload via a matrix‐degradation controlled mechanism upon exposure to oxidative or redox conditions. After surface cloaking with cancer‐cell‐derived membrane fragments, these bioinspired RNase A‐loaded MSNs exhibit homologous targeting and immune‐invasion characteristics inherited from the source cancer cells. The efficient in vitro and in vivo anti‐cancer performance, which includes increased blood circulation time and enhanced tumor accumulation along with low toxicity, suggests that these cell‐membrane‐coated, dual‐responsive degradable MSNs represent a promising platform for the delivery of bio‐macromolecules such as protein and nucleic acid therapeutics. 相似文献
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Nan Chen Min Wei Yanhong Sun Fan Li Hao Pei Xiaoming Li Shao Su Yao He Lianhui Wang Jiye Shi Chunhai Fan Qing Huang 《Small (Weinheim an der Bergstrasse, Germany)》2014,10(2):368-375
Synthetic unmethylated cytosine–guanine (CpG) oligodeoxynucleotides (CpG ODNs) possess high immunostimulatory activity and have been widely used as a therapeutic tool for various diseases including infection, allergies, and cancer. A variety of nanocarriers have been developed for intracellular delivery of CpG ODNs that are otherwise nonpermeable through the cellular membrane. For example, previous studies showed that gold nanoparticles (AuNPs) could efficiently deliver synthetic thiolated CpG ODNs into cultured cells and induce expression of proinflammatory cytokines. Nevertheless, the necessity of using thiolated CpG ODNs for the modification of AuNPs inevitably complicates the synthesis of the nanoconjugates and increases the cost. A new approach is demonstrated for facile assembly of AuNP‐CpG nanoconjugates for cost‐effective drug delivery. It is found that non‐thiolated, diblock ODNs containing a CpG motif and a poly‐adenine (polyA) tail can readily self‐assemble on the surface of AuNPs with controllable and tunable density. Such nanoconjugates are efficiently delivered into RAW264.7 cells and induce immune response in a Toll‐like receptor 9 (TLR9)‐dependent manner. Under optimal conditions, polyA‐CpG‐AuNPs show significantly higher immunostimulatory activity than their thiolated counterpart. In addition, the immunostimulatory activity of CpG‐AuNPs can be modulated by varying the length of the polyA tail. In vivo induction of immune responses in mice is demonstrated by using polyA‐tailed CpG‐AuNP nanoconjugates. 相似文献
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Xiaolin Huang Yaofeng Zhou Lu Ding Guocan Yu Yuankui Leng Weihua Lai Yonghua Xiong Xiaoyuan Chen 《Small (Weinheim an der Bergstrasse, Germany)》2019,15(51)
Herein, a smart supramolecular self‐assembly‐mediated signal amplification strategy is developed on a paper‐based nanobiosensor to achieve the sensitive and customized detection of biomarkers. The host–guest recognition between β‐cyclodextrin‐coated gold nanoparticles (AuNPs) and 1‐adamantane acetic acid or tetrakis(4‐carboxyphenyl)porphyrin is designed and applied to the layer‐by‐layer self‐assembly of AuNPs at the test area of the strip. Thus, the amplified platform exhibits a high sensitivity with a detection limit at subattogram levels (approximately dozens of molecules per strip) and a wide dynamic range of concentration over seven orders of magnitude. The applicability and universality of this sensitive platform are demonstrated in clinically significant ranges to measure carcinoembryonic antigen and HIV‐1 capsid p24 antigen in spiked serum and clinical samples. The customized biomarker detection ability for the on‐demand needs of clinicians is further verified through cycle incubation‐mediated controllable self‐assembly. Collectively, the supramolecular self‐assembly amplification method is suitable as a universal point‐of‐care diagnostic tool and can be readily adapted as a platform technology for the sensitive assay of many different target analytes. 相似文献
16.
Anionic Lipid,pH‐Sensitive Liposome‐Gold Nanoparticle Hybrids for Gene Delivery – Quantitative Research of the Mechanism
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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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Yun Wu Megan Cavanaugh Terp Kwang Joo Kwak Daniel Gallego‐Perez Serge P. Nana‐Sinkam L. James Lee 《Small (Weinheim an der Bergstrasse, Germany)》2013,9(13):2358-2367
Many delivery methods have been developed to improve the therapeutic efficacy and facilitate the clinical translation of nucleic acid‐based therapeutics. A facile surface‐mediated nucleic acid delivery by lipoplexes is prepared in a microwell array, which combines the advantages of lipoplexes as an efficient carrier system, surface‐mediated delivery, and the control of surface topography. Uniform disc‐like lipoplexes containing nucleic acids are formed in the microwell array with a diameter of ~818 nm and thickness of ~195 nm. The microwell array‐mediated delivery of lipoplexes containing FAM‐oligodeoxynucleotides is ~18.6 and ~10.6 times more efficient than the conventional transfection method in an adherent cell line (A549 non‐small cell lung cancer cells) and a suspension cell line (KG‐1a acute myelogenous leukemia cells), respectively. MicroRNA‐29b is then used as a model nucleic acid to investigate the therapeutic efficacy of lipoplexes delivered by the microwell array. Compared to conventional transfection methods, the effective therapeutic dosage of microRNA‐29b is reduced from the microgram level to the nanogram level by lipoplexes prepared in the microwell array. The microwell array is also a very flexible platform. Both nucleic acid therapeutics and imaging reagents are incorporated in lipoplexes and successfully delivered to A549 cells, demonstrating its potential applications in theranostic medicine. 相似文献
19.
Immune Cell‐Mediated Biodegradable Theranostic Nanoparticles for Melanoma Targeting and Drug Delivery
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Zhiwei Xie Yixue Su Gloria B. Kim Erhan Selvi Chuying Ma Virginia Aragon‐Sanabria Jer‐Tsong Hsieh Cheng Dong Jian Yang 《Small (Weinheim an der Bergstrasse, Germany)》2017,13(10)
Although tremendous efforts have been made on targeted drug delivery systems, current therapy outcomes still suffer from low circulating time and limited targeting efficiency. The integration of cell‐mediated drug delivery and theranostic nanomedicine can potentially improve cancer management in both therapeutic and diagnostic applications. By taking advantage of innate immune cell's ability to target tumor cells, the authors develop a novel drug delivery system by using macrophages as both nanoparticle (NP) carriers and navigators to achieve cancer‐specific drug delivery. Theranostic NPs are fabricated from a unique polymer, biodegradable photoluminescent poly (lactic acid) (BPLP‐PLA), which possesses strong fluorescence, biodegradability, and cytocompatibility. In order to minimize the toxicity of cancer drugs to immune cells and other healthy cells, an anti‐BRAF V600E mutant melanoma specific drug (PLX4032) is loaded into BPLP‐PLA nanoparticles. Muramyl tripeptide is also conjugated onto the nanoparticles to improve the nanoparticle loading efficiency. The resulting nanoparticles are internalized within macrophages, which are tracked via the intrinsic fluorescence of BPLP‐PLA. Macrophages carrying nanoparticles deliver drugs to melanoma cells via cell–cell binding. Pharmacological studies also indicate that the PLX4032 loaded nanoparticles effectively kill melanoma cells. The “self‐powered” immune cell‐mediated drug delivery system demonstrates a potentially significant advancement in targeted theranostic cancer nanotechnologies. 相似文献
20.
Super‐Resolution Microscopy Unveils Dynamic Heterogeneities in Nanoparticle Protein Corona
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Natalia Feiner‐Gracia Michaela Beck Sílvia Pujals Sébastien Tosi Tamoghna Mandal Christian Buske Mika Linden Lorenzo Albertazzi 《Small (Weinheim an der Bergstrasse, Germany)》2017,13(41)
The adsorption of serum proteins, leading to the formation of a biomolecular corona, is a key determinant of the biological identity of nanoparticles in vivo. Therefore, gaining knowledge on the formation, composition, and temporal evolution of the corona is of utmost importance for the development of nanoparticle‐based therapies. Here, it is shown that the use of super‐resolution optical microscopy enables the imaging of the protein corona on mesoporous silica nanoparticles with single protein sensitivity. Particle‐by‐particle quantification reveals a significant heterogeneity in protein absorption under native conditions. Moreover, the diversity of the corona evolves over time depending on the surface chemistry and degradability of the particles. This paper investigates the consequences of protein adsorption for specific cell targeting by antibody‐functionalized nanoparticles providing a detailed understanding of corona‐activity relations. The methodology is widely applicable to a variety of nanostructures and complements the existing ensemble approaches for protein corona study. 相似文献