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1.
A universal platform for the efficient intracellular delivery of biomacromolecules with minimal trauma to the cells is highly desirable for biological research and clinical applications. Moreover, such a platform should include the ability to harvest the “engineered” cells, for particular in vitro or ex vivo conditions. Herein, a broadly applicable platform is presented with integrated multifunctions based on silicon nanowire arrays (SiNWAs) modified with a sugar‐responsive polymer containing phenylboronic acid (PBA) groups. Due to the synergistic effects of the specific recognition of PBA groups by sialic acid and “nanoenhancement” by the SiNWAs, this system shows a high capture capacity for both surface adherent and suspension cells overexpressing sialic acid on the membrane. Under appropriate near‐infrared irradiation, the photothermal properties of SiNWAs endow this system with high efficiency to deliver biomacromolecules into the captured cells by a membrane disruption mechanism. The cells thus “engineered” can be harvested simply by treatment with a nontoxic sugar solution, thereby maintaining good viability for subsequent applications. This method appears to have strong potential for the intracellular delivery of diverse biomacromolecules into both surface adherent and suspension cells, including hard‐to‐transfect suspension T cells, and may open up new pathways for engineering living cells.  相似文献   

2.
The synergistic combination of photothermal and RNA interference therapy demonstrates great potential for effective treatment of metastatic breast cancer, but their efficacy is limited by the poor delivery efficiency to tumor. Herein, it is reported that an albumin biomimetic nanocorona (DRI‐S@HSA) can accomplish the high accumulation and deep penetration within tumor tissues, thereby holding great promise for synergistic therapy. DRI‐S@HSA is prepared by camouflaging human serum albumin (HSA) onto an IR‐780 and small interfering RNA‐loaded cell‐penetrating peptide nanoassembly (DRI‐S). In metastatic 4T1 breast cancer cells, DRI‐S@HSA can be largely internalized, and cause significant inhibition on cell migration and proliferation in combination with laser irradiation. Surprisingly, in vivo, the albumin camouflage in DRI‐S@HSA produces a 2.5‐fold enhancement on tumor accumulation compared to the undecorated DRI‐S, and dramatically improves the deep penetration capacity in tumor mass. Moreover, a single DRI‐S@HSA treatment plus 808 nm laser irradiation results in an 83.6% inhibition on tumor growth and efficient prevention of lung metastases. Taken together, the findings can provide an encouraging biomimetic tumor‐targeted drug delivery strategy to inhibit tumor progression and prevent lung metastases of breast cancer.  相似文献   

3.
The synthesis and characterization of a gold nanoparticle functionalized mesoporous silica nanoparticle (Au‐MSN) platform for codelivery of proteins and plasmid DNA to plant tissues using a biolistic particle delivery system is reported. The in vitro uptake and release profiles of fluorescently labeled bovine serum albumin (BSA) and enhanced green fluorescent protein (eGFP) are investigated. As a proof‐of‐concept demonstration, Au‐MSN with large average pore diameters (10 nm) are shown to deliver and subsequently release proteins and plasmid DNA to the same cell after passing through the plant cell wall upon bombardment. Release of fluorescent eGFP indicates the delivery of active, non‐denatured proteins to plant cells. This advance represents the first example of biolistic‐mediated codelivery of proteins and plasmid DNA to plant cells via gold‐functionalized MSN and provides a powerful tool for both fundamental and applied research of plant sciences.  相似文献   

4.
A near‐infrared (NIR) light‐triggered nanocarrier is developed for intracellular controlled release with good stability, high nuclease resistance, and good biocompatibility. The nanocarrier consists of a gold nanorod core and mesoporous silica shell, capped with reversible single‐stranded DNA valves, which are manipulated by switching between the laser on/off states. Upon laser irradiation, the valves of the nanocarrier open and the cargo molecules can be released from the mesopores. When the NIR laser is turned off, the valves close and the nanocarrier stops releasing the cargo molecules. The release amount of the cargo molecules can be controlled precisely by adjusting the irradiation time and the laser on‐off cycles. Confocal fluorescence imaging shows that the nanocarrier can be triggered by the laser irradiation and the controlled release can be accomplished in living cells. Moreover, the therapeutic effect toward cancer cells can also be regulated when the chemotherapeutic drug doxorubicin is loaded into the nanocarrier. This novel approach provides an ideal platform for drug delivery by a NIR light‐activated mechanism with precise control of area, time, and especially dosage.  相似文献   

5.
The higher DNA delivery efficiency into plants by gold nanoparticles embedded in sharp carbonaceous carriers is demonstrated. These nanogold‐embedded carbon matrices are prepared by heat treatment of biogenic intracellular gold nanoparticles. The DNA‐delivery efficiency is tested on a model plant, Nicotiana tabacum, and is further extended to the monocot, Oryza sativa, and a hard dicot tree species, Leucaena leucocephala. These materials reveal good dispersion of the transport material, producing a greater number of GUS foci per unit area. The added advantages of the composite carrier are the lower plasmid and gold requirements. Plant‐cell damage with the carbon‐supported particles is very minimal and can be gauged from the increased plant regeneration and transformation efficiency compared with that of the commercial micrometer‐sized gold particles. This is ascribed to the sharp edges that the carbon supports possess, which lead to better piercing capabilities with minimum damage.  相似文献   

6.
A smart drug delivery system integrating both photothermal therapy and chemotherapy for killing cancer cells is reported. The delivery system is based on a mesoporous silica‐coated Pd@Ag nanoplates composite. The Pd@Ag nanoplate core can effectively absorb and convert near infrared (NIR) light into heat. The mesoporous silica shell is provided as the host for loading anticancer drug, doxorubicin (DOX). The mesoporous shell consists of large pores, ~10 nm in diameter, and allows the DOX loading as high as 49% in weight. DOX loaded core–shell nanoparticles exhibit a higher efficiency in killing cancer cells than free DOX. More importantly, DOX molecules are loaded in the mesopores shell through coordination bonds that are responsive to pH and heat. The release of DOX from the core‐shell delivery vehicles into cancer cells can be therefore triggered by the pH drop caused by endocytosis and also NIR irradiation. A synergistic effect of combining chemotherapy and photothermal therapy is observed in our core‐shell drug delivery system. The cell‐killing efficacy by DOX‐loaded core–shell particles under NIR irradiation is higher than the sum of chemotherapy by DOX‐loaded particles and photothermal therapy by core–shell particles without DOX.  相似文献   

7.
Biomimetic microsystems, which can be driven by various stimuli, are an emerging field in micro/nano‐technology and nano‐medicine. In this study, a soft and fast‐response robotic platform, constituted by PDMS/graphene‐nanoplatelets composited layer (PDMS/GNPs) and pristine PDMS layer, is presented. Due to the differences in coefficient of thermal expansion and Young's modulus of the two layers, the bilayer platform can be driven to bend to the PDMS/GNPs side by light irradiation. The robotic platform (1 mm in width and 7 mm in length) can be deflected about 1500 μm by near infrared irradiation (nIR)(808 nm in wavelength) within 3.4 s, and excellent reversibility and repeatability in actuation are also revealed by sweeping and multicycle light irradiation. The experiments also show that, the presented bilayer platform in various shapes, that is, fish‐like shapes, can float and swim to perspective location in fluid (i.e., water), whose moving directions and velocities can be remotely adjusted by light, indicating an excellent light‐actuation ability and well controllability. The results may be not only hopeful in developing light‐driven drug‐delivery platform, but also the bio‐robotic microgrippers applying in vivo and in vitro.  相似文献   

8.
A novel multifunctional drug‐delivery platform is developed based on cholesteryl succinyl silane (CSS) nanomicelles loaded with doxorubicin, Fe3O4 magnetic nanoparticles, and gold nanoshells (CDF‐Au‐shell nanomicelles) to combine magnetic resonance (MR) imaging, magnetic‐targeted drug delivery, light‐triggered drug release, and photothermal therapy. The nanomicelles show improved drug‐encapsulation efficiency and loading level, and a good response to magnetic fields, even after the formation of the gold nanoshell. An enhancement for T2‐weighted MR imaging is observed for the CDF‐Au‐shell nanomicelles. These nanomicelles display surface plasmon absorbance in the near‐infrared (NIR) region, thus exhibiting an NIR (808 nm)‐induced temperature elevation and an NIR light‐triggered and stepwise release behavior of doxorubicin due to the unique characteristics of the CSS nanomicelles. Photothermal cytotoxicity in vitro confirms that the CDF‐Au‐shell nanomicelles cause cell death through photothermal effects only under NIR laser irradiation. Cancer cells incubated with CDF‐Au‐shell nanomicelles show a significant decrease in cell viability only in the presence of both NIR irradiation and a magnetic field, which is attributed to the synergetic effects of the magnetic‐field‐guided drug delivery and the photothermal therapy. Therefore, such multicomponent nanomicelles can be developed as a smart and promising nanosystem that integrates multiple capabilities for effective cancer diagnosis and therapy.  相似文献   

9.
Gold nanoparticles (GNPs) are nontoxic, can be functionalized with ligands, and preferentially accumulate in tumors. We have developed a 13.56-MHz RF-electromagnetic field (RF-EM) delivery system capable of generating high E-field strengths required for noninvasive, noncontact heating of GNPs. The bulk heating and specific heating rates were measured as a function of NP size and concentration. It was found that heating is both size and concentration dependent, with 5 nm particles producing a 50.6 ± 0.2 °C temperature rise in 30 s for 25 μg/mL gold (125 W input). The specific heating rate was also size and concentration dependent, with 5 nm particles producing a specific heating rate of 356 ± 78 kW/g gold at 16 μg/mL (125 W input). Furthermore, we demonstrate that cancer cells incubated with GNPs are killed when exposed to 13.56 MHz RF-EM fields. Compared to cells that were not incubated with GNPs, three out of four RF-treated groups showed a significant enhancement of cell death with GNPs (p<0.05). GNP-enhanced cell killing appears to require temperatures above 50 °C for the experimental parameters used in this study. Transmission electron micrographs show extensive vacuolization with the combination of GNPs and RF treatment.  相似文献   

10.
The possibility of regulating cell signaling with high spatial and temporal resolution within individual cells and complex cellular networks has important implications in biomedicine. This article demonstrates a general strategy that uses near‐infrared tissue‐penetrating laser pulses to uncage biomolecules from plasmonic gold‐coated liposomes, i.e., plasmonic liposomes, to activate cell signaling in a nonthermal, ultrafast, and highly controllable fashion. Near‐infrared picosecond laser pulse induces transient nanobubbles around plasmonic liposomes. The mechanical force generated from the collapse of nanobubbles rapidly ejects encapsulated compound within 0.1 ms. This article shows that single pulse irradiation triggers the rapid intracellular uncaging of calcein from plasmonic liposomes inside endolysosomes. The uncaged calcein then evenly distributes over the entire cytosol and nucleus. Furthermore, this article demonstrates the ability to trigger calcium signaling in both an immortalized cell line and primary dorsal root ganglion neurons by intracellular uncaging of inositol triphosphate (IP3), an endogenous cell calcium signaling second messenger. Compared with other uncaging techniques, this ultrafast near‐infrared light‐driven molecular uncaging method is easily adaptable to deliver a wide range of bioactive molecules with an ultrafast optical switch, enabling new possibilities to investigate signaling pathways within individual cells and cellular networks.  相似文献   

11.
This study develops multimodal magnetic nanoclusters (M‐MNCs) for gene transfer, directed migration, and tracking of human mesenchymal stem cells (hMSCs). The M‐MNCs are designed with 5 nm iron oxide nanoparticles and a fluorescent dye (i.e., Rhodamine B) in the matrix of the Food and Drug Administration approved polymer poly(lactide‐co‐glycolide) using a nanoemulsion method. The synthesized M‐MNCs have a hydrodynamic diameter of ≈150 nm, are internalized by stem cells via endocytosis, and deliver genes with high efficiency. The cellular internalization and gene expression efficiency of the clustered nanoparticles are significantly higher than that of single nanoparticles. The M‐MNC‐labeled hMSCs migrate upon application of a magnetic force and can be visualized by both optical and magnetic resonance (MR) imaging. In animal models, the M‐MNC‐labeled hMSCs are also successfully tracked using optical and MR imaging. Thus, the M‐MNCs not only allow the efficient delivery of genes to stem cells but also the tracking of cells in animal models. Taken together, the results show that this new type of nanocomposite can be of great help in future stem cell research and in the development of cell‐based therapeutic agents.  相似文献   

12.
As tumors employ complementary overlapping and/or independent mechanisms to evade immune surveillance, many emerging cancer immunotherapies attempt to target multiple pathways to eradicate malignant cells. Although modulation of independent pathways by simultaneous administration of multiple immune modulators (e.g., checkpoint inhibitors, cytokines, and growth factors) has shown great promise, the clinical impact remains limited due to severe toxicity associated with high systemic levels of many of these drugs. Therefore, novel platforms for efficient delivery of multi‐component therapies at lower effective doses would be enabling. Here, a drug delivery platform called immunomodulatory molecule delivery system (iMods), which provides sustained extracellular delivery of a checkpoint inhibitor (anti‐PD‐L1) and simultaneously, targeted intracellular delivery of a tumor antigen (OVA) along with adjuvant (poly(I:C)), and the indoleamine deoxygenase inhibitor 1‐MT is described. In melanoma tumor‐bearing mice, combinatorial delivery of these factors with iMods leads to regression of both treated and untreated (contralateral) melanoma tumors and 100% survival. These promising therapeutic outcomes are attributed to significantly enhanced ratios of anti‐tumor CD8 T‐cell/tumor‐protective regulatory T‐cell (Treg) in tumors and tumor draining lymph nodes. Overall, the iMods delivery platform described here represents a promising advance in multi‐factor cancer immunotherapy.  相似文献   

13.
Biocompatible, multifunctional, stimuli responsive, and high drug loading capacity are key factors for the new generation of drug delivery platforms. However, it is extremely challenging to create such a platform that inherits all these advanced properties in a single carrier. Herein, porous silicon nanoparticles (PSi NPs) and giant liposomes are assembled on a microfluidic chip as an advanced nano‐in‐micro platform (PSi NPs@giant liposomes), which can co‐load and co‐deliver hydrophilic and hydrophobic drugs combined with synthesized DNA nanostructures, short gold nanorods, and magnetic nanoparticles. The PSi NPs@giant liposomes with photothermal and magnetic responsiveness show good biocompatibility, high loading capacity, and controllable release. The hydrophilic thermal oxidized PSi NPs encapsulate hydrophobic therapeutics within the hydrophilic core of the giant liposomes, endowing high therapeutics loading capacity with tuneable ratio and controllable release. It is demonstrated that the DAO‐E A DNA nanostructures have synergism with drugs and importantly they contribute to the significant enhancement of cell death to doxorubicin‐resistant MCF‐7/DOX cells, overcoming the multidrug resistance in the cancer cells. Therefore, the PSi NPs@giant liposomes nano‐in‐micro platform hold great potential for a cocktail delivery of drugs and DNA nanostructures for effective cancer therapy, controllable drug release with tuneable therapeutics ratio, and both photothermal and magnetic dual responsiveness.  相似文献   

14.
A novel photo‐responsive protein–graphene–protein (PGP) capsule that doubles as a photothermal agent with core/shell structure is constructed by anchoring reduced graphene oxide nanosheets on one‐component protein (lactoferrin) shell through a double emulsion method. PGP capsules can transport fully concealed hydrophilic anticancer cargo, doxorubicin (Dox), with a large payload (9.43 μmol g‐1) to be later unloaded in a burst‐like manner by photo‐actuation triggered by near‐infrared irradiation. Being biocompatible yet with a high cancer cell targeting efficiency, PGP capsules have successfully eradicated subcutaneous tumors in 10 d following a single 5 min NIR irradiation without distal damage. Besides, the photochemothermal therapy of PGP capsules eradicates tumor cells not only in the light‐treating area but also widely light‐omitted tumor cells, overcoming the tumor recurrence due to efficient cell killing efficacy. These results demonstrate that the PGP capsule is a potential new drug delivery platform for local‐targeting, on‐demand, photoresponsive, combined chemotherapy/hyperthermia for tumor treatment and other biomedical applications.  相似文献   

15.
The cell‐specific targeting drug delivery and controlled release of drug at the cancer cells are still the main challenges for anti‐breast cancer metastasis therapy. Herein, the authors first report a biomimetic drug delivery system composed of doxorubicin (DOX)‐loaded gold nanocages (AuNs) as the inner cores and 4T1 cancer cell membranes (CMVs) as the outer shells (coated surface of DOX‐incorporated AuNs (CDAuNs)). The CDAuNs, perfectly utilizing the natural cancer cell membranes with the homotypic targeting and hyperthermia‐responsive ability to cap the DAuNs with the photothermal property, can realize the selective targeting of the homotypic tumor cells, hyperthermia‐triggered drug release under the near‐infrared laser irradiation, and the combination of chemo/photothermal therapy. The CDAuNs exhibit a stimuli‐release of DOX under the hyperthermia and a high cell‐specific targeting of the 4T1 cells in vitro. Moreover, the excellent combinational therapy with about 98.9% and 98.5% inhibiting rates of the tumor volume and metastatic nodules is observed in the 4T1 orthotopic mammary tumor models. As a result, CDAuNs can be a promising nanodelivery system for the future therapy of breast cancer.  相似文献   

16.
The interfacing of soft and hard electronics is a key challenge for flexible hybrid electronics. Currently, a multisubstrate approach is employed, where soft and hard devices are fabricated or assembled on separate substrates, and bonded or interfaced using connectors; this hinders the flexibility of the device and is prone to interconnect issues. Here, a single substrate interfacing approach is reported, where soft devices, i.e., sensors, are directly printed on Kapton polyimide substrates that are widely used for fabricating flexible printed circuit boards (FPCBs). Utilizing a process flow compatible with the FPCB assembly process, a wearable sensor patch is fabricated composed of inkjet‐printed gold electrocardiography (ECG) electrodes and a stencil‐printed nickel oxide thermistor. The ECG electrodes provide 1 mVpp ECG signal at 4.7 cm electrode spacing and the thermistor is highly sensitive at normal body temperatures, and demonstrates temperature coefficient, α ≈ –5.84% K–1 and material constant, β ≈ 4330 K. This sensor platform can be extended to a more sophisticated multisensor platform where sensors fabricated using solution processable functional inks can be interfaced to hard electronics for health and performance monitoring, as well as internet of things applications.  相似文献   

17.
As the second most common cause of cancer‐related death worldwide, colorectal cancer (CRC) requires novel therapy strategies. Biodegradable polymers are used as drug carriers for treating CRC and other cancers. However, one of the limitations for the polymeric drug carriers is that they do not directly involve the treating procedure. Herein, to develop a polymeric drug delivery system with additional therapeutic effect from that of the polymer itself, poly(ursolic acid) (PUA) is, for the first time, simply synthesized via polycondensation of ursolic acid (UA), a bioactive ingredient widely distributed in herbal medicine. PUA can self‐assemble into nanoparticles (PUA‐NPs) with a diameter of ≈122 nm and an effective load of ≈10.1%, and deliver drugs, such as paclitaxel (PUA‐NPs@PTX). In vitro studies show that PUA‐NPs@PTX have strong cytotoxicity against colorectal cancer CT26 cells, while in vivo results indicate that these NPs have a prolonged blood circulation time, enhanced tumor accumulation, and significantly improved antitumor efficacy in CT26 tumor‐bearing mice. Furthermore, both in vitro and in vivo results confirm that the PUA‐NPs themselves have therapeutic effects on CT26 cells, without causing obvious toxicity to main organs, such as bledding or necrosis. In summary, such a therapeutic polymer platform provides a new therapeutic strategy for treating cancer.  相似文献   

18.
Smart drug delivery systems with on‐demand drug release capability are rather attractive to realize highly specific cancer treatment. Herein, a novel light‐responsive drug delivery platform based on photosensitizer chlorin e6 (Ce6) doped mesoporous silica nanorods (CMSNRs) is developed for on‐demand light‐triggered drug release. In this design, CMSNRs are coated with bovine serum albumin (BSA) via a singlet oxygen (SO)‐sensitive bis‐(alkylthio)alkene (BATA) linker, and then modified with polyethylene glycol (PEG). The obtained CMSNR‐BATA‐BSA‐PEG, namely CMSNR‐B‐PEG, could act as a drug delivery carrier to load with either small drug molecules such as doxorubicin (DOX), or larger macromolecules such as cis‐Pt (IV) pre‐drug conjugated third generation dendrimer (G3‐Pt), both of which are sealed inside the mesoporous structure of nanorods by BSA coating. Upon 660 nm light irradiation with a rather low power density, CMSNRs with intrinsic Ce6 doping would generate SO to cleave BATA linker, inducing detachment of BSA‐PEG from the nanorod surface and thus triggering release of loaded DOX or G3‐Pt. As evidenced by both in vitro and in vivo experiments, such CMSNR‐B‐PEG with either DOX or G3‐Pt loading offers remarkable synergistic therapeutic effects in cancer treatment, owing to the on‐demand release of therapeutics specifically in the tumor under light irradiation.  相似文献   

19.
The combination of cell microenvironment control and real‐time monitoring of cell signaling events can provide key biological information. Through precise multipatterning of gold nanoparticles (GNPs) around cells, sensing and actuating elements can be introduced in the cells' microenviroment, providing a powerful substrate for cell studies. In this work, a combination of techniques are implemented to engineer complex substrates for cell studies. Alternating GNPs and bioactive areas are created with micrometer separation by means of a combination of vacumm soft‐lithography of GNPs and protein microcontract printing. Instead of conventional microfluidics that need syringe pumps to flow liquid in the microchannels, degas driven flow is used to fill dead‐end channels with GNP solutions, rendering the fabrication process straightforward and accessible. This new combined technique is called Printing and Vacuum lithography (PnV lithography). By using different GNPs with various organic coating ligands, different macroscale patterns are obtained, such as wires, supercrystals, and uniformly spread nanoparticle layers that can find different applications depending on the need of the user. The application of the system is tested to pattern a range of mammalian cell lines and obtain readouts on cell viability, cell morphology, and the presence of cell adhesive proteins.  相似文献   

20.
王家伟  李斌  张检民  冯国斌  刘卫平  韦成华  韩永超  王娜 《红外与激光工程》2023,52(1):20220329-1-20220329-8
为了研究以激光为热源开展材料高温力学性能测试的可行性,建立理论模型与数值模型,分析了材料在双面均匀激光光斑加热下的表面及内部温升。结果表明,理想情况下采用均匀化激光双面辐照的加热方式可以在试件加热区域内形成较均匀的温度场。为验证上述结论,建立了光斑匀化度达92%的激光双面辐照热力耦合测试试验平台,并基于相关测试方法获取了传统加热方式难以快速加热的CFRP层合板高温拉伸强度。结果表明,试件在激光加热中心测试区域(10 mm×10 mm)内的温度均匀性良好。试件在均匀化激光双面辐照下可被快速加热至923℃,测试区域内的最大温度波动为6.8%。文中提出的基于均匀化激光双面辐照的热力耦合测试方法相比传统测试方法具有通用性好、温升率高、测试温度高、测试效率高等一系列的优点。该研究可为进一步研制通用型材料/结构高温升率、高温力学性能试验系统提供关键技术支撑。  相似文献   

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