Journal Of Nanomedicine & Nanotechnology[JOURNAL]
Sun
168 papers
Optical properties of biomimetic probes engineered from erythrocytes.
Burns JM, Saager R, Majaron B … +2 more , Jia W, Anvari B
Nanotechnology · 2017 Jan · PMID 27966473 · Full text
Light-activated theranostic materials offer a potential platform for optical imaging and phototherapeutic applications. We have engineered constructs derived from erythrocytes, which can be doped with the FDA-approved ne...
Light-activated theranostic materials offer a potential platform for optical imaging and phototherapeutic applications. We have engineered constructs derived from erythrocytes, which can be doped with the FDA-approved near infrared (NIR) chromophore, indocyanine green (ICG). We refer to these constructs as NIR erythrocyte-mimicking transducers (NETs). Herein, we investigated the effects of changing the NETs mean diameter from micron- (≈4 μm) to nano- (≈90 nm) scale, and the ICG concentration utilized in the fabrication of NETs from 5 to 20 μM on the resulting absorption and scattering characteristics of the NETs. Our approach consisted of integrating sphere-based measurements of light transmittance and reflectance, and subsequent utilization of these measurements in an inverse adding-doubling algorithm to estimate the absorption (μ ) and reduced scattering (μ ') coefficients of these NETs. For a given NETs diameter, values of μ increased over the approximate spectral band of 630-860 nm with increasing ICG concentration. Micron-sized NETs produced the highest peak value of μ when using ICG concentrations of 10 and 20 μM, and showed increased values of μ ' as compared to nano-sized NETs. Spectral profiles of μ ' for these NETs showed a trend consistent with Mie scattering behavior for spherical objects. For all NETs investigated, changing the ICG concentration minimally affected the scattering characteristics. A Monte Carlo-based model of light distribution showed that the presence of these NETs enhanced the fluence levels within simulated blood vessels. These results provide important data towards determining the appropriate light dosimetry parameters for an intended light-based biomedical application of NETs.
Functionalized gold nanoparticles manifested as potent carriers for nucleolar targeting.
Shahbazi R, Ozcicek I, Ozturk G … +1 more , Ulubayram K
Nanotechnology · 2017 Jan · PMID 27924783 · Publisher ↗
It is generally known that gold nanoparticles are localised in the cytoplasm and, if synthesised in small sizes or functionalized with specific proteins, they enter the cell nucleus. However, there is no report emphasisi...
It is generally known that gold nanoparticles are localised in the cytoplasm and, if synthesised in small sizes or functionalized with specific proteins, they enter the cell nucleus. However, there is no report emphasising the importance of surface functionalization in their accumulation in the nucleolus. Here, for the first time in the literature, it is proposed that functionalization of gold nanoparticles with a thin layer of polyethyleneimine (PEI) spearheads them to the nucleolus of hard-to-transfect post-mitotic dorsal root ganglion neurones in a size-independent manner. As a potential for theranostic applications, it was found that functionalization with a thin layer of PEI affected the emission signal intensity of gold nanoparticles so that the cellular biodistribution of nanoparticles was visualised clearly under both confocal and two-photon microscopes.
Targeted chimera delivery to ovarian cancer cells by heterogeneous gold magnetic nanoparticle.
Chen Y, Xu M, Guo Y … +7 more , Tu K, Wu W, Wang J, Tong X, Wu W, Qi L, Shi D
Nanotechnology · 2017 Jan · PMID 27906685 · Publisher ↗
Efficient delivery of small interfering RNAs (siRNAs) to the targeted cells has remained a significant challenge in clinical applications. In the present study, we developed a novel aptamer-siRNA chimera delivery system...
Efficient delivery of small interfering RNAs (siRNAs) to the targeted cells has remained a significant challenge in clinical applications. In the present study, we developed a novel aptamer-siRNA chimera delivery system mediated by cationic Au-FeO nanoparticles (NPs). The chimera constructed by VEGF RNA aptamer and Notch3 siRNA was bonded with heterogeneous Au-FeO nanoparticles by electrostatic interaction. The obtained complex exhibited much higher silencing efficiency against Notch3 gene compared with chimera alone and lipofectamine-siRNA complex, and improved the antitumor effects of the loaded chimera. Moreover, the efficient delivery of the chimera by Au-FeO NPs could reverse multi-drug resistance (MDR) of ovarian cancer cells against the chemotherapeutic drug cisplatin, indicating its potential capability for future targeted cancer therapy while overcoming MDR.
Fabrication and in vitro characterization of gadolinium-based nanoclusters for simultaneous drug delivery and radiation enhancement.
Yoo SS, Guo L, Sun X … +4 more , Shaw AR, Yuan Z, Löbenberg R, Roa WH
Nanotechnology · 2016 Sep · PMID 27533280 · Publisher ↗
We report the synthesis of a gadolinium hydroxide (Gd(OH)3) nanorod based doxorubicin (Dox) delivery system that can enhance both magnetic resonance imaging contrast and radiation sensitivity. A simple and cost effective...
We report the synthesis of a gadolinium hydroxide (Gd(OH)3) nanorod based doxorubicin (Dox) delivery system that can enhance both magnetic resonance imaging contrast and radiation sensitivity. A simple and cost effective wet-chemical method was utilized in the presence of manganese (Mn) ions and Dox to produce the Gd(OH)3:Mn·Dox nanocluster structure. The Gd(OH)3:Mn·Dox nanocluster was composed of Mn-doped Gd(OH)3 nanorods arranged in parallel with Dox as a linker molecule between the adjacent nanorods. No other studies have utilized Dox as both the linker and therapeutic molecule in a nanostructure to date. The Gd(OH)3 nanorod is reported to have no significant cellular or in vivo toxicity, which makes it an ideal base material for this biomedical application. The Gd(OH)3:Mn·Dox nanocluster exhibited paramagnetic behavior and was stable in a colloidal solution. The nanocluster also enabled high Dox loading capacity and specifically released Dox in a sustained and pH-dependent manner. The positively charged Gd(OH)3:Mn·Dox nanoclusters were readily internalized into MDA-MB-231 breast cancer cells via endocytosis, which resulted in intracellular release of Dox. The released Dox in cells was effective in conferring cytotoxicity and inhibiting proliferation of cancer cells. Furthermore, a synergistic anticancer effect could be observed with radiation treatment. Overall, the Gd(OH)3:Mn·Dox nanocluster drug delivery system described herein may have potential utility in clinics as a multifunctional theranostic nanoparticle with combined benefits in both diagnosis and therapy in the management of cancer.
Versatile theranostics agents designed by coating ferrite nanoparticles with biocompatible polymers.
Zahraei M, Marciello M, Lazaro-Carrillo A … +9 more , Villanueva A, Herranz F, Talelli M, Costo R, Monshi A, Shahbazi-Gahrouei D, Amirnasr M, Behdadfar B, Morales MP
Nanotechnology · 2016 Jun · PMID 27184442 · Publisher ↗
Three biocompatible polymers, polyethylene glycol (PEG), dextran and chitosan, have been used in this work to control the colloidal stability of magnetic nanoparticles (14 ± 5 nm in diameter) and to vary the aggregation...
Three biocompatible polymers, polyethylene glycol (PEG), dextran and chitosan, have been used in this work to control the colloidal stability of magnetic nanoparticles (14 ± 5 nm in diameter) and to vary the aggregation state in order to study their effect on relaxometric and heating properties. Two different coating strategies have been deeply developed; one based on the formation of an amide bond between citric acid coated nanoparticles (NPs) and amine groups present on the polymer surface and the other based on the NP encapsulation. Relaxometric properties revealed that proton relaxation rates strongly depend on the coating layer hydrophilicity and the aggregation state of the particles due to the presence of magnetic interactions. Thus, while PEG coating reduces particle aggregation by increasing inter-particle spacing leading to reduction of both T1 and T2 relaxation, dextran and chitosan lead to an increase mainly in T2 values due to the aggregation of particles in bigger clusters where they are in close contact. Dextran and chitosan coated NPs have also shown a remarkable heating effect during the application of an alternating magnetic field. They have proved to be potential candidates as theranostic agents for cancer diagnosis and treatment. Finally, cytotoxicity of PEG conjugated NPs, which seem to be ideal for intravenous administration because of their small hydrodynamic size, was investigated resulting in high cell viability even at 0.2 mg Fe ml(-1) after 24 h of incubation. This suspension can be used as drug/biomolecule carrier for in vivo applications.
Barium titanate nanoparticles: promising multitasking vectors in nanomedicine.
Genchi GG, Marino A, Rocca A … +2 more , Mattoli V, Ciofani G
Nanotechnology · 2016 Jun · PMID 27145888 · Publisher ↗
Ceramic materials based on perovskite-like oxides have traditionally been the object of intense interest for their applicability in electrical and electronic devices. Due to its high dielectric constant and piezoelectric...
Ceramic materials based on perovskite-like oxides have traditionally been the object of intense interest for their applicability in electrical and electronic devices. Due to its high dielectric constant and piezoelectric features, barium titanate (BaTiO3) is probably one of the most studied compounds of this family. Recently, an increasing number of studies have been focused on the exploitation of barium titanate nanoparticles (BTNPs) in the biomedical field, owing to the high biocompatibility of BTNPs and their peculiar non-linear optical properties that have encouraged their use as nanocarriers for drug delivery and as label-free imaging probes. In this review, we summarize all the recent findings about these 'smart' nanoparticles, including the latest, most promising potential as nanotransducers for cell stimulation.
Polypyrrole-based nanotheranostics for activatable fluorescence imaging and chemo/photothermal dual therapy of triple-negative breast cancer.
Park D, Ahn KO, Jeong KC … +1 more , Choi Y
Nanotechnology · 2016 May · PMID 27004751 · Publisher ↗
Here, we fabricated polypyrrole nanoparticles (PPys) (termed HA10-PPy, HA20-PPy, and HA40-PPy) doped with different average molecular weight hyaluronic acids (HAs) (10, 20, and 40 kDa, respectively), and evaluated the ef...
Here, we fabricated polypyrrole nanoparticles (PPys) (termed HA10-PPy, HA20-PPy, and HA40-PPy) doped with different average molecular weight hyaluronic acids (HAs) (10, 20, and 40 kDa, respectively), and evaluated the effect of molecular weight of doped HA on photothermal induction, fluorescence quenching, and drug loading efficiencies. Doxorubicin-loaded HA-doped PPys (DOX@HA-PPys) could be used for imaging and therapy of triple-negative breast cancer (TNBC). Fluorescence turn-on, stimuli-responsive drug release, and photo-induced heating of DOX@HA-PPys enabled not only activatable fluorescence imaging but also subsequent chemo/photothermal dual therapy for TNBC. In particular, we illustrated the potential usefulness of the photothermal effect of the nanoparticles for overcoming chemoresistance in TNBC.
Interactions and effects of BSA-functionalized single-walled carbon nanotubes on different cell lines.
Muzi L, Tardani F, La Mesa C … +3 more , Bonincontro A, Bianco A, Risuleo G
Nanotechnology · 2016 Apr · PMID 26926913 · Publisher ↗
Functionalized carbon nanotubes (CNTs) have shown great promise in several biomedical contexts, spanning from drug delivery to tissue regeneration. Thanks to their unique size-related properties, single-walled CNTs (SWCN...
Functionalized carbon nanotubes (CNTs) have shown great promise in several biomedical contexts, spanning from drug delivery to tissue regeneration. Thanks to their unique size-related properties, single-walled CNTs (SWCNTs) are particularly interesting in these fields. However, their use in nanomedicine requires a clear demonstration of their safety in terms of tissue damage, toxicity and pro-inflammatory response. Thus, a better understanding of the cytotoxicity mechanisms, the cellular interactions and the effects that these materials have on cell survival and on biological membranes is an important first step for an appropriate assessment of their biocompatibility. In this study we show how bovine serum albumin (BSA) is able to generate homogeneous and stable dispersions of SWCNTs (BSA-CNTs), suggesting their possible use in the biomedical field. On the other hand, this study wishes to shed more light on the impact and the interactions of protein-stabilized SWCNTs with two different cell types exploiting multidisciplinary techniques. We show that BSA-CNTs are efficiently taken up by cells. We also attempt to describe the effect that the interaction with cells has on the dielectric characteristics of the plasma membrane and ion flux using electrorotation. We then focus on the BSA-CNTs' acute toxicity using different cellular models. The novel aspect of this work is the evaluation of the membrane alterations that have been poorly investigated to date.
Nanoporous capsules of block co-polymers of [(MeO-PEG-NH)-b-(L-GluA)]-PCL for the controlled release of anticancer drugs for therapeutic applications.
Amgoth C, Dharmapuri G, Kalle AM … +1 more , Paik P
Nanotechnology · 2016 Mar · PMID 26891479 · Publisher ↗
Herein, new nanoporous capsules of the block co-polymers of MeO-PEG-NH-(L-GluA)10 and polycaprolactone (PCL) have been synthesized through a surfactant-free cost-effective self-assembled soft-templating approach for the...
Herein, new nanoporous capsules of the block co-polymers of MeO-PEG-NH-(L-GluA)10 and polycaprolactone (PCL) have been synthesized through a surfactant-free cost-effective self-assembled soft-templating approach for the controlled release of drugs and for therapeutic applications. The nanoporous polymer capsules are designed to be biocompatible and are capable of encapsulating anticancer drugs (e.g., doxorubicin hydrochloride (DOX) and imatinib mesylate (ITM)) with a high extent (∼279 and ∼480 ng μg(-1), respectively). We have developed a nanoformulation of porous MeO-PEG-NH-(L-GluA)10-PCL capsules with DOX and ITM. The porous polymer nanoformulations have been programmed in terms of the release of anticancer drugs with a desired dose to treat the leukemia (K562) and human carcinoma cells (HepG2) in vitro and show promising IC50 values with a very high mortality of cancer cells (up to ∼96.6%). Our nanoformulation arrests the cell divisions due to 'cellular scenescence' and kills the cancer cells specifically. The present findings could enrich the effectiveness of idiosyncratic nanoporous polymer capsules for use in various other nanomedicinal and biomedical applications, such as for killing cancer cells, immune therapy, and gene delivery.
Synthetic nanoparticles camouflaged with biomimetic erythrocyte membranes for reduced reticuloendothelial system uptake.
Rao L, Xu JH, Cai B … +7 more , Liu H, Li M, Jia Y, Xiao L, Guo SS, Liu W, Zhao XZ
Nanotechnology · 2016 Feb · PMID 26820630 · Publisher ↗
Suppression of the reticuloendothelial system (RES) uptake is one of the most challenging tasks in nanomedicine. Coating stratagems using polymers, such as poly(ethylene glycol) (PEG), have led to great success in this r...
Suppression of the reticuloendothelial system (RES) uptake is one of the most challenging tasks in nanomedicine. Coating stratagems using polymers, such as poly(ethylene glycol) (PEG), have led to great success in this respect. Nevertheless, recent observations of immunological response toward these synthetic polymers have triggered a search for better alternatives. In this work, natural red blood cell (RBC) membranes are camouflaged on the surface of Fe3O4 nanoparticles for reducing the RES uptake. In vitro macrophage uptake, in vivo biodistribution and pharmacokinetic studies demonstrate that the RBC membrane is a superior alternative to the current gold standard PEG for nanoparticle 'stealth'. Furthermore, we systematically investigate the in vivo potential toxicity of RBC membrane-coated nanoparticles by blood biochemistry, whole blood panel examination and histology analysis based on animal models. The combination of synthetic nanoparticles and natural cell membranes embodies a novel and biomimetic nanomaterial design strategy and presents a compelling property of functional materials for a broad range of biomedical applications.
A multi-functional nanoplatform for tumor synergistic phototherapy.
Zhang H, Jiao X, Chen Q … +4 more , Ji Y, Zhang X, Zhu X, Zhang Z
Nanotechnology · 2016 Feb · PMID 26808235 · Publisher ↗
Phototherapy, which mainly includes photothermal treatment (PTT) and photodynamic treatment (PDT), is a photo-initiated, noninvasive and effective approach for cancer treatment. The high accumulation of photosensitizers...
Phototherapy, which mainly includes photothermal treatment (PTT) and photodynamic treatment (PDT), is a photo-initiated, noninvasive and effective approach for cancer treatment. The high accumulation of photosensitizers (PSs) in a targeted tumor is still a major challenge for efficient light conversion, to generate reactive oxygen species (ROS) and local hyperthermia. In this study, a simple and efficient hyaluronic acid (HA)-modified nanoplatform (HA-TiO2@MWCNTs) with high tumor-targeting ability, excellent phototherapy efficiency, low light-associated side effects and good water solubility was developed. It could be an effective carrier to load hematoporphyrin monomethyl ether (HMME), owing to the tubular conjugate structure. Apart from this, the as-prepared TiO2@MWCNTs nanocomposites could also be used as PSs for tumor PTT and PDT. Those results in vitro and in vivo showed that the anti-tumor effect of this system-mediated PTT/PDT were significantly better than those of single treatment manner. In addition, this drug delivery system could realize high ratio of drug loading, sustained drug release, prolonged circulation in vivo and active targeted accumulation in tumor. These results suggest that HA-TiO2@MWCNTs/HMME has high potential for tumor synergistic phototherapy as a smart theranostic nanoplatform.
WO3/Pt nanoparticles promote light-induced lipid peroxidation and lysosomal instability within tumor cells.
Clark AJ, Petty HR
Nanotechnology · 2016 Feb · PMID 26788907 · Publisher ↗
Although metal-metal oxide nanoparticles have attracted considerable interest as catalysts, they have attracted little interest in nanomedicine. This is likely due to the fact that metal oxide semiconductors generally re...
Although metal-metal oxide nanoparticles have attracted considerable interest as catalysts, they have attracted little interest in nanomedicine. This is likely due to the fact that metal oxide semiconductors generally require biologically harmful ultraviolet excitation. In contrast, this study focuses upon WO3/Pt nanoparticles, which can be excited by visible light. To optimize the nanoparticles' catalytic performance, platinization was performed at alkaline pH. These nanoparticles destroyed organic dyes, consumed dissolved oxygen and produced hydroxyl radicals. 4T1 breast cancer cells internalized WO3/Pt nanoparticles within the membrane-bound endo-lysosomal compartment as shown by electron and fluorescence microscopy. During visible light exposure, but not in darkness, WO3/Pt nanoparticles manufacture reactive oxygen species, promote lipid peroxidation, and trigger lysosomal membrane disruption. As cells of the immune system degrade organic molecules, produce reactive oxygen species, and activate the lipid peroxidation pathway within target cells, these nanoparticles mimic the chemical attributes of immune effector cells. These biomimetic nanoparticles should become useful in managing certain cancers, especially ocular cancer.
Multifunctionalized iron oxide nanoparticles for selective drug delivery to CD44-positive cancer cells.
Aires A, Ocampo SM, Simões BM … +10 more , Josefa Rodríguez M, Cadenas JF, Couleaud P, Spence K, Latorre A, Miranda R, Somoza Á, Clarke RB, Carrascosa JL, Cortajarena AL
Nanotechnology · 2016 Feb · PMID 26754042 · Publisher ↗
Nanomedicine nowadays offers novel solutions in cancer therapy and diagnosis by introducing multimodal treatments and imaging tools in one single formulation. Nanoparticles acting as nanocarriers change the solubility, b...
Nanomedicine nowadays offers novel solutions in cancer therapy and diagnosis by introducing multimodal treatments and imaging tools in one single formulation. Nanoparticles acting as nanocarriers change the solubility, biodistribution and efficiency of therapeutic molecules, reducing their side effects. In order to successfully apply these novel therapeutic approaches, efforts are focused on the biological functionalization of the nanoparticles to improve the selectivity towards cancer cells. In this work, we present the synthesis and characterization of novel multifunctionalized iron oxide magnetic nanoparticles (MNPs) with antiCD44 antibody and gemcitabine derivatives, and their application for the selective treatment of CD44-positive cancer cells. The lymphocyte homing receptor CD44 is overexpressed in a large variety of cancer cells, but also in cancer stem cells (CSCs) and circulating tumor cells (CTCs). Therefore, targeting CD44-overexpressing cells is a challenging and promising anticancer strategy. Firstly, we demonstrate the targeting of antiCD44 functionalized MNPs to different CD44-positive cancer cell lines using a CD44-negative non-tumorigenic cell line as a control, and verify the specificity by ultrastructural characterization and downregulation of CD44 expression. Finally, we show the selective drug delivery potential of the MNPs by the killing of CD44-positive cancer cells using a CD44-negative non-tumorigenic cell line as a control. In conclusion, the proposed multifunctionalized MNPs represent an excellent biocompatible nanoplatform for selective CD44-positive cancer therapy in vitro.
Multifunctional nanosheets based on folic acid modified manganese oxide for tumor-targeting theranostic application.
Hao Y, Wang L, Zhang B … +8 more , Zhao H, Niu M, Hu Y, Zheng C, Zhang H, Chang J, Zhang Z, Zhang Y
Nanotechnology · 2016 Jan · PMID 26629735 · Publisher ↗
It is highly desirable to develop smart nanocarriers with stimuli-responsive drug-releasing and diagnostic-imaging functions for cancer theranostics. Herein, we develop a reduction and pH dual-responsive tumor theranosti...
It is highly desirable to develop smart nanocarriers with stimuli-responsive drug-releasing and diagnostic-imaging functions for cancer theranostics. Herein, we develop a reduction and pH dual-responsive tumor theranostic platform based on degradable manganese dioxide (MnO2) nanosheets. The MnO2 nanosheets with a size of 20-60 nm were first synthesized and modified with (3-Aminopropyl) trimethoxysilane (APTMS) to get amine-functionalized MnO2, and then functionalized by NH2-PEG2000-COOH (PEG). The tumor-targeting group, folic acid (FA), was finally conjugated with the PEGylated MnO2 nanosheets. Then, doxorubicin (DOX), a chemotherapeutic agent, was loaded onto the modified nanosheets through a physical adsorption, which was designated as MnO2-PEG-FA/DOX. The prepared MnO2-PEG-FA/DOX nanosheets with good biocompatibility can not only efficiently deliver DOX to tumor cells in vitro and in vivo, leading to enhanced anti-tumor efficiency, but can also respond to a slightly acidic environment and high concentration of reduced glutathione (GSH), which caused degradation of MnO2 into manganese ions enabling magnetic resonance imaging (MRI). The longitudinal relaxation rate r1 was 2.26 mM(-1) s(-1) at pH 5.0 containing 2 mM GSH. These reduction and pH dual-responsive biodegradable nanosheets combining efficient MRI and chemotherapy provide a novel and promising platform for tumor-targeting theranostic application.
Nanoimaging: photophysical and pharmaceutical characterization of poly-lactide-co-glycolide nanoparticles engineered with quantum dots.
Pederzoli F, Ruozi B, Pracucci E … +6 more , Signore G, Zapparoli M, Forni F, Vandelli MA, Ratto G, Tosi G
Nanotechnology · 2016 Jan · PMID 26597894 · Publisher ↗
Quantum dots (QDs) and polymeric nanoparticles (NPs) are considered good binomials for the development of multifunctional nanomedicines for multimodal imaging. Fluorescent imaging of QDs can monitor the behavior of QD-la...
Quantum dots (QDs) and polymeric nanoparticles (NPs) are considered good binomials for the development of multifunctional nanomedicines for multimodal imaging. Fluorescent imaging of QDs can monitor the behavior of QD-labeled NPs in both cells and animals with high temporal and spatial resolutions. The comprehension of polymer interaction with the metallic QD surface must be considered to achieve a complete chemicophysical characterization of these systems and to describe the QD optical properties to be used for their unequivocal identification in the tissue. In this study, by comparing two different synthetic procedures to obtain polymeric nanoparticles labeled with QDs, we investigated whether their optical properties may change according to the formulation methods, as a consequence of the different polymeric environments. Atomic force microscopy, transmission electron microscopy, confocal and fluorescence lifetime imaging microscopy characterization demonstrated that NPs modified with QDs after the formulation process (post-NPs-QDs) conserved the photophysical features of the QD probe. In contrast, by using a polymer modified with QDs to formulate NPs (pre-NPs-QDs), a significant quenching of QD fluorescence and a blueshift in its emission spectra were observed. Our results suggest that the packaging of QDs into the polymeric matrix causes a modification of the QD optical properties: these effects must be characterized in depth and carefully considered when developing nanosystems for imaging and biological applications.
Towards a minimally invasive sampling tool for high resolution tissue analytical mapping.
Gottardi R
Nanotechnology · 2015 Sep · PMID 26302485 · Publisher ↗
Multiple spatial mapping techniques of biological tissues have been proposed over the years, but all present limitations either in terms of resolution, analytical capacity or invasiveness. Ren et al (2015 Nanotechnology...
Multiple spatial mapping techniques of biological tissues have been proposed over the years, but all present limitations either in terms of resolution, analytical capacity or invasiveness. Ren et al (2015 Nanotechnology 26 284001) propose in their most recent work the use of a picosecond infrared laser (PIRL) under conditions of ultrafast desorption by impulsive vibrational excitation (DIVE) to extract small amounts of cellular and molecular components, conserving their viability, structure and activity. The PIRL DIVE technique would then work as a nanobiopsy with minimal damage to the surrounding tissues, which could potentially be applied for high resolution local structural characterization of tissues in health and disease with the spatial limit determined by the laser focus.
Real time macrophage migration analysis and associated pro-inflammatory cytokine release on transparent carbon nanotube/polymer composite nano-film.
Khang D
Nanotechnology · 2015 Aug · PMID 26202827 · Publisher ↗
Surface chemistry and nanoscale surface morphology are both influential factors for cell adhesion, growth, and differentiation. In particular, cell migration is one of the major markers of initial immune response activat...
Surface chemistry and nanoscale surface morphology are both influential factors for cell adhesion, growth, and differentiation. In particular, cell migration is one of the major markers of initial immune response activation to implanted biomaterials. Despite their indication, it has been difficult to directly examine macrophages on nanoscale materials, because most nanomaterials possess greater thicknesses than nanoscale. This study developed transparent films comprising a carbon nanotube and polymer composite with controlled surface stiffness and nanoscale roughness. As nanoscale surface topography can incite immune cell activation, analysis of the real-time cell migration (including velocity) of macrophages due to changes in nanoscale surface topography of a biopolymer can support the direct relationship between initial macrophage dynamics and corresponding pro-inflammatory responses. Through real-time analysis, we have identified that surface chemistry and surface nanoscale topography are both independent factors mediating macrophage interactions, and, thus, immune cell behavior can be further controlled by the systematic variation of nanoscale surface topography for a given surface chemistry. Considering that the initial immune response can determine the fate and lifetime of implanted biomaterials, this study presents the direct relationship between initial macrophage dynamics and subsequent inflammatory cytokine release on transparent carbon nanotube polymer composites.
Statistical prediction of nanoparticle delivery: from culture media to cell.
Brown MR, Hondow N, Brydson R … +3 more , Rees P, Brown AP, Summers HD
Nanotechnology · 2015 Apr · PMID 25797791 · Publisher ↗
The application of nanoparticles (NPs) within medicine is of great interest; their innate physicochemical characteristics provide the potential to enhance current technology, diagnostics and therapeutics. Recently a numb...
The application of nanoparticles (NPs) within medicine is of great interest; their innate physicochemical characteristics provide the potential to enhance current technology, diagnostics and therapeutics. Recently a number of NP-based diagnostic and therapeutic agents have been developed for treatment of various diseases, where judicious surface functionalization is exploited to increase efficacy of administered therapeutic dose. However, quantification of heterogeneity associated with absolute dose of a nanotherapeutic (NP number), how this is trafficked across biological barriers has proven difficult to achieve. The main issue being the quantitative assessment of NP number at the spatial scale of the individual NP, data which is essential for the continued growth and development of the next generation of nanotherapeutics. Recent advances in sample preparation and the imaging fidelity of transmission electron microscopy (TEM) platforms provide information at the required spatial scale, where individual NPs can be individually identified. High spatial resolution however reduces the sample frequency and as a result dynamic biological features or processes become opaque. However, the combination of TEM data with appropriate probabilistic models provide a means to extract biophysical information that imaging alone cannot. Previously, we demonstrated that limited cell sampling via TEM can be statistically coupled to large population flow cytometry measurements to quantify exact NP dose. Here we extended this concept to link TEM measurements of NP agglomerates in cell culture media to that encapsulated within vesicles in human osteosarcoma cells. By construction and validation of a data-driven transfer function, we are able to investigate the dynamic properties of NP agglomeration through endocytosis. In particular, we statistically predict how NP agglomerates may traverse a biological barrier, detailing inter-agglomerate merging events providing the basis for predictive modelling of nanopharmacology.
Triggered-release polymeric conjugate micelles for on-demand intracellular drug delivery.
Cao Y, Gao M, Chen C … +6 more , Fan A, Zhang J, Kong D, Wang Z, Peer D, Zhao Y
Nanotechnology · 2015 Mar · PMID 25708980 · Publisher ↗
Nanoscale drug delivery platforms have been developed over the past four decades that have shown promising clinical results in several types of cancer and inflammatory disorders. These nanocarriers carrying therapeutic p...
Nanoscale drug delivery platforms have been developed over the past four decades that have shown promising clinical results in several types of cancer and inflammatory disorders. These nanocarriers carrying therapeutic payloads are maximizing the therapeutic outcomes while minimizing adverse effects. Yet one of the major challenges facing drug developers is the dilemma of premature versus on-demand drug release, which influences the therapeutic regiment, efficacy and potential toxicity. Herein, we report on redox-sensitive polymer-drug conjugate micelles for on-demand intracellular delivery of a model active agent, curcumin. Biodegradable methoxy poly(ethylene glycol)-poly(lactic acid) copolymer (mPEG-PLA) was conjugated with curcumin via a disulfide bond or ester bond (control), respectively. The self-assembled redox-sensitive micelles exhibited a hydrodynamic size of 115.6 ± 5.9 (nm) with a zeta potential of -10.6 ± 0.7 (mV). The critical micelle concentration was determined at 6.7 ± 0.4 (μg mL(-1)). Under sink conditions with a mimicked redox environment (10 mM dithiothreitol), the extent of curcumin release at 48 h from disulfide bond-linked micelles was nearly three times higher compared to the control micelles. Such rapid release led to a lower half maximal inhibitory concentration (IC50) in HeLa cells at 18.5 ± 1.4 (μg mL(-1)), whereas the IC50 of control micelles was 41.0 ± 2.4 (μg mL(-1)). The cellular uptake study also revealed higher fluorescence intensity for redox-sensitive micelles. In conclusion, the redox-sensitive polymeric conjugate micelles could enhance curcumin delivery while avoiding premature release, and achieving on-demand release under the high glutathione concentration in the cell cytoplasm. This strategy opens new avenues for on-demand drug release of nanoscale intracellular delivery platforms that ultimately might be translated into pre-clinical and future clinical practice.
Multifunctional PEG modified DOX loaded mesoporous silica nanoparticle@CuS nanohybrids as photo-thermal agent and thermal-triggered drug release vehicle for hepatocellular carcinoma treatment.
Wu L, Wu M, Zeng Y … +4 more , Zhang D, Zheng A, Liu X, Liu J
Nanotechnology · 2015 Jan · PMID 25517859 · Publisher ↗
The combination of a multi-therapeutic mode with a controlled fashion is a key improvement in nanomedicine. Here, we synthesized polyethylene glycol (PEG)-modified doxorubicin (DOX)-loaded mesoporous silica nanoparticle...
The combination of a multi-therapeutic mode with a controlled fashion is a key improvement in nanomedicine. Here, we synthesized polyethylene glycol (PEG)-modified doxorubicin (DOX)-loaded mesoporous silica nanoparticle (MSN) @CuS nanohybrids as efficient drug delivery carriers, combined with photothermal therapy and chemotherapy to enhance the therapeutic efficacy on hepatocellular carcinoma (HCC). The physical properties of the nanohybrids were characterized by transmission electron microscopy (TEM), N2 adsorption and desorption experiments and by the Vis-NIR absorption spectra. The results showed that the doxorubicin could be stored in the inner pores of mesoporous silica nanoparticles; the CuS nanoparticles, which are coated on the surface of a mesoporous silica nanoparticle, could serve as efficient photothermal therapy (PTT) agents; the loaded drug release could be easily triggered by NIR irradiation. The combination of the PTT treatment with controlled chemotherapy could further enhance the cancer ablation ability compared to any of the single approaches alone. Hence, the reported PEG-modified DOX-loaded mesoporous silica nanoparticle@CuS nanohybrids might be very promising therapeutic agents for HCC treatment.
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