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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clusters of metal nanoparticles with an overall size of less than 100 nm and high metal loadings for strong optical functionality are of interest in various fields including microelectronics, sensors, optoelectronics, and biomedical imaging and therapeutics. Herein we assemble approximately 5 nm gold particles into clusters with controlled size, as small as 30 nm and up to 100 nm, that contain only small amounts of polymeric stabilizers. The assembly is kinetically controlled with weakly adsorbing polymers, PLA(2K)-b-PEG(10K)-b-PLA(2K) or PEG (MW = 3350), by manipulating electrostatic, van der Waals (VDW), steric, and depletion forces. The cluster size and optical properties are tuned as a function of particle volume fractions and polymer/gold ratios to modulate the interparticle interactions. The close spacing between the constituent gold nanoparticles and high gold loadings (80-85 w/w gold) produce a strong absorbance cross section of approximately 9 x 10(-15) m(2) in the NIR at 700 nm. This morphology results from VDW and depletion attractive interactions that exclude the weakly adsorbed polymeric stabilizer from the cluster interior. The generality of this kinetic assembly platform is demonstrated for gold nanoparticles with a range of surface charges from highly negative to neutral with the two different polymers.
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PMID:Kinetic assembly of near-IR-active gold nanoclusters using weakly adsorbing polymers to control the size. 2036 35

The primary focus of this work was to develop activatable probes suitable for in vivo detection of phospholipase activity. Phospholipases (PLs) are ubiquitous enzymes that perform a number of critical regulatory functions. They catalyze phospholipid breakdown and are categorized as A(1), A(2) (PLA(2)), C (PLC), and D (PLD) based on their site of action. Here, we report the design, synthesis, and characterization of self-quenching reporter probes that release fluorescent moieties upon cleavage with PLA(2) or PLC. A series of phospholipids were synthesized bearing the NIR fluorophore pyropheophorbide a (Pyro) at the sn-2 position. Fluorescence quenching was achieved by attachment of either a positively charged black hole quencher-3 (BHQ-3) to the phospholipid headgroup or another neutral Pyro moiety at the sn-1 position. The specificity to different phospholipases was modulated by insertion of spacers (C(6), C(12)) between Pyro and the lipid backbone. The specificity of the quenched fluorescent phospholipids was assayed on a plate reader against a number of phospholipases and compared with two commercial probes bearing the visible fluorophore BODIPY. While PyroC(6)-PyroC(6)-PtdCho revealed significant background fluorescence, and a 10% fluorescence increase under the action of PLA(2), Pyro-PtdEtn-BHQ demonstrated high selective sensitivity to PLC, particularly to the PC-PLC isoform, and its sensitivity to PLA(2) was negligible due to steric hindrance at the sn-2 position. In contrast, the C(12)-spacered PyroC(12)-PtdEtn-BHQ demonstrated a remarkable selectivity for PLA(2) and the best relative PLA(2)/PLC sensitivity, significantly outperforming previously known probes. These results open an avenue for future in vivo experiments and for new probes to detect PL activity.
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PMID:Design and synthesis of phospholipase C and A2-activatable near-infrared fluorescent smart probes. 2088 56

Although sub-100 nm nanoclusters of metal nanoparticles are of interest in many fields including biomedical imaging, sensors, and catalysis, it has been challenging to control their morphologies and chemical properties. Herein, a new concept is presented to assemble equilibrium Au nanoclusters of controlled size by tuning the colloidal interactions with a polymeric stabilizer, PLA(1k)-b-PEG(10k)-b-PLA(1k). The nanoclusters form upon mixing a dispersion of ~5 nm Au nanospheres with a polymer solution followed by partial solvent evaporation. A weakly adsorbed polymer quenches the equilibrium nanocluster size and provides steric stabilization. Nanocluster size is tuned from ~20 to ~40 nm by experimentally varying the final Au nanoparticle concentration and the polymer/Au ratio, along with the charge on the initial Au nanoparticle surface. Upon biodegradation of the quencher, the nanoclusters reversibly and fully dissociate to individual ~5 nm primary particles. Equilibrium cluster size is predicted semiquantitatively with a free energy model that balances short-ranged depletion and van der Waals attractions with longer-ranged electrostatic repulsion, as a function of the Au and polymer concentrations. The close spacings of the Au nanoparticles in the clusters produce strong NIR extinction over a broad range of wavelengths from 650 to 900 nm, which is of practical interest in biomedical imaging.
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PMID:Equilibrium gold nanoclusters quenched with biodegradable polymers. 2323 Sep 5

A strategy of using a gold nanorod (GNR)-loaded electrospun membrane as a photothermal therapy platform of cancer is reported. The strategy takes both the advantages of the excellent photothermal properties of GNRs to selectively kill the cancerous cells, and the widely used biodegradable electrospun membrane to serve as GNR-carrier and surgical recovery material. PEG modified GNRs were embedded into the electrospun fibrous membrane which was composed of PLGA and PLA-b-PEG with an 85:15 ratio. After incubation with the cells in the cell culture medium, the PEG-GNRs were released from the membrane and taken up by cancer cells, allowing the generation of heat upon NIR irradiation to induce cancer cell death. We have demonstrated that the use of PEG-GNR-embedded membrane selectively killed the cancerous cells and effectively inhibited cancer cell proliferation though in vitro experiments. The PEG-GNRs-loaded membrane is a promising material for postsurgical recovery of cancer.
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PMID:Gold nanorod-embedded electrospun fibrous membrane as a photothermal therapy platform. 2443 24

Hot-melt extrusion and 3D printing are enabling manufacturing approaches for patient-centred medicinal products. Hot-melt extrusion is a flexible and continuously operating technique which is a crucial part of a typical processing cycle of printed medicines. In this work we use hot-melt extrusion for manufacturing of medicinal films containing indomethacin (IND) and polycaprolactone (PCL), extruded strands with nitrofurantoin monohydrate (NFMH) and poly (ethylene oxide) (PEO), and feedstocks for 3D printed dosage forms with nitrofurantoin anhydrate (NFAH), hydroxyapatite (HA) and poly (lactic acid) (PLA). These feedstocks were printed into a prototype solid dosage form using a desktop 3D printer. These model formulations were characterized using near-infrared chemical imaging (NIR-CI) and, more specifically, the image analytical data were analysed using multivariate curve resolution-alternating least squares (MCR-ALS). The MCR-ALS algorithm predicted the spatial distribution of IND and PCL in the films with reasonable accuracy. In the extruded strands both the chemical mapping of the components in the formulation as well as the solid form of the active compound could be visualized. Based on the image information the total nitrofurantoin and PEO contents could be estimated., The dehydration of NFMH to NFAH, a process-induced solid form change, could be visualized as well. It was observed that the level of dehydration increased with increasing processing time (recirculation during the mixing phase of molten PEO and nitrofurantoin). Similar results were achieved in the 3D printed solid dosage forms produced from the extruded feedstocks. The results presented in this work clearly demonstrate that NIR-CI in combination with MCR-ALS can be used for chemical mapping of both active compound and excipients, as well as for visualization of solid form variation in the final product. The suggested NIR-CI approach is a promising process control tool for characterization of innovative patient-centred medicinal products.
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PMID:Near-infrared chemical imaging (NIR-CI) of 3D printed pharmaceuticals. 2772 Aug 77

While it has been well recognized that affordable and pocket-size devices play a major role in environmental monitoring, food safety and medical diagnostics, it often takes a tremendous amount of resources to develop such devices. Devices that have been developed are often dedicated devices that can detect only one or a few targets. To overcome these limitations, we herein report a novel target-responsive smart thermometer for translating molecular detection into a temperature test. The sensor system consists of a functional DNA-phospholipase A2 (PLA2) enzyme conjugate, a liposome-encapsulated NIR dye, and a thermometer interfaced with a NIR-laser device. The sensing principle is based on the target-induced release of PLA2 from the DNA-enzyme conjugate, which catalyzes the hydrolysis of liposome to release the NIR dye inside the liposome. Upon NIR-laser irradiation, the released dye can convert excitation energy into heat, producing a temperature increase in solution, which is detectable using a thermometer. Considering the low cost and facile incorporation of the system with suitable functional DNAs to recognize many targets, the system demonstrated here makes the thermometer an affordable and pocket-size meter for the detection and quantification of a wide range of targets.
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PMID:Translating molecular detections into a simple temperature test using a target-responsive smart thermometer. 2978 May 21

Aberrant regulation of angiogenesis supply sufficient oxygen and nutrients to exacerbate tumor progression and metastasis. Taking this hallmark of cancer into account, reported here is a self-monitoring and triple-collaborative therapy system by auto-fluorescent polymer nanotheranostics which could be concurrently against angiogenesis and tumor cell growth by combining the benefits of anti-angiogenesis, RNA interfere and photothermal therapy (PTT). Auto-fluorescent amphiphilic polymer polyethyleneimine-polylactide (PEI-PLA) with positive charge can simultaneously load hydrophobic antiangiogenesis agent combretastatin A4 (CA4), NIR dye IR825 and absorb negatively charged heat shock protein 70 (HSP70) inhibitor (siRNA against HSP70) to construct self-monitoring nanotheranostics (NPICS). NPICS can effectively restrain the expression of HSP70 to reduce their endurance to the IR825-mediated PTT, leading to an enhanced photocytotoxicity. In a xenograft mouse tumor model, NPICS show an effect of inhibition of tumor angiogenesis and also display a highly synergistic anticancer efficacy with NIR laser irradiation. Significantly, based on its inherent auto-fluorescence, PEI-PLA not only serves as the drug carrier, but also as the self-monitor to real-time track NPICS biodistribution and tumor accumulation via fluorescence imaging. Moreover, IR825 endows NPICS could also be used as photoacoustic (PA) agents for in vivo PA imaging. This nanoplatform shows enormous potentials in cancer theranostics.
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PMID:Auto-fluorescent polymer nanotheranostics for self-monitoring of cancer therapy via triple-collaborative strategy. 3059 Feb 40

A novel multifunctional theranostic agent has been successfully fabricated by loading iron oxide nanoparticles into poly(lactic acid) (PLA) microcapsules followed by surface functionalization with graphene oxide. Both in vitro and in vivo experiments proved that the resulting microcapsules could serve as contrast agents to simultaneously enhance ultrasound, magnetic resonance and photoacoustic imaging. The composite microcapsules show good biocompatibility and rapid response to magnetic fields. Due to the strong absorption of the near-infrared light, the composite microcapsules could efficiently kill cancer cells upon NIR laser irradiation. In addition, it was found that such a photothermal effect could be obviously enhanced by applying an external magnetic field. In a nutshell, this multifunctional microcapsule can be developed as a promising platform that integrates multimodality imaging and therapy capabilities for effective cancer theranostics.
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PMID:Imaging guided photothermal therapy using iron oxide loaded poly(lactic acid) microcapsules coated with graphene oxide. 3226 9

This study is to develop a novel itraconazole-loaded nanoparticle (ITZ-NP) platform for effective antifungal therapy. First, the monomethoxypoly(ethylene glycol)-b-poly(lactic acid) (mPEG-b-PLA) copolymer was prepared as a drug carrier material. Then the nanoparticles were formulated via a simple film hydration method. The copolymer and nanoparticles were characterized by standard methods, including 1H NMR, 13C NMR, FT-NIR, DSC, XRPD, and particle size, zeta potential, morphology and physical examination. Furthermore, in vitro itraconazole release and antifungal activity were intensively evaluated. The results showed that the formed nanoparticles significantly enhanced sustained drug release and inhibited fungal infection. In addition, ITZ-NPs caused very mild hemolysis and slight venous irritation, indicating much better biocompatibility than marketed cyclodextrin formulations of ITZ. An Iin vivo biodistribution study via intravenous injection showed that ITZ-NPs could be effectively retained in blood circulation and selectively distributed in RES-rich organs compared with commercial cyclodextrin injection, with the verification of Re, Te, RTe and Ce. In summary, the developed ITZ-NPs could reduce systemic toxicity, improve antifungal activity and act as a potential intravenous formulation of ITZ.
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PMID:Development of an itraconazole encapsulated polymeric nanoparticle platform for effective antifungal therapy. 3226 56

The development of targeted delivery systems can improve the selectivity of cancer drugs. Additionally, a system that promotes the controlled delivery of the drug triggered by an external stimulus in the exact target tissue is highly desirable. Regarding the light stimulus, the NIR window (650-950 nm) is the most suitable due to its higher capacity of penetration in human tissues and less harmful effects on normal cells. In this work, new red-light-responsive nanoparticles for doxorubicin delivery were developed. The nanoparticles were based on cleavable di-block copolymers of poly(ethylene glycol) (PEG) and poly(lactic acid) (PLA) linked by a red-light sensitive segment (1,2-bis(2-hydroxyethylthio)ethylene, BHETE). The PEG-BHETE-PLA copolymers were synthesized under mild conditions and exhibited a narrow polydispersity. The nanoparticles presented a size between 53 and 133 nm, with a doxorubicin loading capacity between 1.2 and 4.4 wt%. Release study of the encapsulated doxorubicin confirms the light-triggered nanoparticle disassembly process. In vitro cytotoxicity tests in MCF7 cell line, for the light-triggered nanoparticles, showed a decrease in cancer cells' viability higher than 25% compared to non-irradiated cells. Due to the promising results obtained with the light-sensitive PEG-BHETE-PLA nanoparticles, these materials have great potential to be used in drug delivery systems for cancer therapy.
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PMID:Development of red-light cleavable PEG-PLA nanoparticles as delivery systems for cancer therapy. 3297 40


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