Zelepukin IV, Yaremenko AV, Petersen EV
… +4 more, Deyev SM, Cherkasov VR, Nikitin PI, Nikitin MP
Nanotechnology
· 2019 Mar · PMID 30572321
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Nanoparticles (NPs) are among the most promising agents for advanced theranostics. However, their functioning in vivo is severely inhibited by the mononuclear phagocyte system (MPS), which rapidly removes all foreign ent...Nanoparticles (NPs) are among the most promising agents for advanced theranostics. However, their functioning in vivo is severely inhibited by the mononuclear phagocyte system (MPS), which rapidly removes all foreign entities from blood circulation. Little is known about the sequestration mechanisms and the ways to counteract them. New methods are highly demanded for investigation with high scrutiny of each aspect of NP clearance from blood. For example, while liver macrophages capture the majority of the administered particles, reliable investigation of this process in absence of other MPS components is hard to implement in vivo. Here, we demonstrate a novel method for real-time investigation hepatic uptake of NPs in an isolated perfused liver based on an extremely accurate magnetometric registration technique. The signal is obtained solely from the magnetic NPs without any 'background' from blood or tissues, which is a significant advantage over other techniques, e.g. optical ones. We illustrate the method capacity by investigation of behavior of different particles and show good correlation with in vivo studies. We also demonstrate notable suitability of the method for studying the NP clearance from the flow in the user-defined mediums, e.g. those containing specific serum components. Finally, the method was applied to reveal an interesting effect of short-term decrease of liver macrophage activity after the first interaction with small amounts of NPs. The developed perfusion model based on the high-performance magnetometry can be used for finding new mechanisms of NP sequestration and for development of novel 'stealth' nanoagents.
Nanotechnology
· 2019 Feb · PMID 30523911
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Development of a safe, efficient and inexpensive multifunctional nanoplatform using a facile approach for multimodal imaging and therapeutic functions becomes more and more practically relevant but challenging. In this w...Development of a safe, efficient and inexpensive multifunctional nanoplatform using a facile approach for multimodal imaging and therapeutic functions becomes more and more practically relevant but challenging. In this work, we demonstrated a novel nanocomposites (BiS-Gd) for computed tomography (CT)/magnetic resonance (MR) imaging-guided photothermal therapy (PTT) for cancer in vitro. It was achieved by modification of hydrophobic BiS with a smart amphiphilic gadolinium-chelated ligand. The as-prepared nanocomposites composed of low-cost BiS and gadolinium complexes, showed high stability, excellent biocompatibility and good photostability. It was observed that BiS-Gd nanocomposites can efficiently convert the NIR light into heat, and then suppressed the growth of tumor cells under NIR laser irradiation. Apart from serving as an effective photothermal agent, the as-prepared nanomaterials could induce an efficient contrast enhancement for both CT and MR imaging at low concentrations of Bi and Gd, rendering more accurate diagnosis. This work suggests the potential of BiS-Gd nanomaterials as a novel multifunctional nanoplatform for CT/MR imaging-guided PTT for cancer.
Nanotechnology
· 2018 Dec · PMID 30215611
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Nanomedicines are engineered nanoscale structures that have an extensive range of application in the diagnosis and therapy of many diseases. Despite the rapid progress in and tremendous potential of nanomedicines, their...Nanomedicines are engineered nanoscale structures that have an extensive range of application in the diagnosis and therapy of many diseases. Despite the rapid progress in and tremendous potential of nanomedicines, their clinical translational process is still slow, owing to the difficulty in understanding, evaluating, and predicting their behavior in complex living organisms. Microfluidic techniques offer a promising way to resolve these challenges. Carefully designed microfluidic chips enable in vivo microenvironment simulation and high-throughput analysis, thus providing robust platforms for nanomedicine evaluation. Here, we summarize the recent developments and achievements in microfluidic methods for nanomedicine evaluation, categorized into four sections based on their target systems: single cell, multicellular system, organ, and organism levels. Finally, we provide our perspectives on the challenges and future directions of microfluidics-based nanomedicine evaluation.
Wang L, Cai Y, An Z
… +3 more, Gu W, Chen P, Cai Q
Nanotechnology
· 2018 Dec · PMID 30207290
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Here we report a novel drug delivery system using mesoporous inner-empty upconversion microspheres carrying drugs with ZnO quantum dots (UCMPS@ZnO) acting as a 'door-keeper' for pH-triggered drug release. Compared to oth...Here we report a novel drug delivery system using mesoporous inner-empty upconversion microspheres carrying drugs with ZnO quantum dots (UCMPS@ZnO) acting as a 'door-keeper' for pH-triggered drug release. Compared to other upconversion drug delivery systems, it is smarter, simpler, more efficient and more biocompatible. In particular, the UCMPS@ZnO microspheres show low cytotoxicity, are simple to produce and have a high drug loading rate (15%). Promisingly, a mice treatment experiment demonstrated that the multifunctional nanoparticles have efficient inhibition of tumor growth after a 14-day treatment. This makes UCMPS@DOX-ZnO microspheres a promising theranostic candidate in cancer treatment and clinical trials.
Nanotechnology
· 2018 Dec · PMID 30192236
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Nanoparticles are submicrometer in size and are used in a variety of ways in the biomedical field. They can carry therapeutic drugs, either in the particle core or surface to target cancer sites in the body. Additionally...Nanoparticles are submicrometer in size and are used in a variety of ways in the biomedical field. They can carry therapeutic drugs, either in the particle core or surface to target cancer sites in the body. Additionally they can contain imaging agents to diagnose and monitor the tumor size using different imaging modalities, such as fluorescence and nuclear magnetic resonance imaging. Novel theranostic nanoparticle agents, called perfluorohexane nanoemulsions (PFH-NEs) were synthesized whose intrinsic properties could be used for both imaging (ultrasound and photoacoustic) and therapy. Compared to other theranostic agents, our PFH-NEs can absorb sufficient near-infrared light to enhance contrast and provide deeper penetration imaging at laser fluences causing minimal damage to healthy tissue. One contrast mechanism (optical absorption/photoacoustics) allows us to validate localization of the agent and another (acoustic impedance/ultrasound) allows the imaging of therapeutic delivery after particle activation. In this work, we show the potential of these PFH-NEs to be used as multimodal imaging agents and for therapy.
Borišev I, Mrđanovic J, Petrovic D
… +5 more, Seke M, Jović D, Srđenović B, Latinovic N, Djordjevic A
Nanotechnology
· 2018 Aug · PMID 29798934
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Nanotechnology, focused on discovery and development of new pharmaceutical products is known as nanopharmacology, and one research area this branch is engaged in are nanopharmaceuticals. The importance of being nano has...Nanotechnology, focused on discovery and development of new pharmaceutical products is known as nanopharmacology, and one research area this branch is engaged in are nanopharmaceuticals. The importance of being nano has been particularly emphasized in scientific areas dealing with nanomedicine and nanopharmaceuticals. Nanopharmaceuticals, their routes of administration, obstacles and solutions concerning their improved application and enhanced efficacy have been briefly yet comprehensively described. Cancer is one of the leading causes of death worldwide and evergrowing number of scientific research on the topic only confirms that the needs have not been completed yet and that there is a wide platform for improvement. This is undoubtedly true for nanoformulations of an anticancer drug doxorubicin, where various nanocarrriers were given an important role to reduce the drug toxicity, while the efficacy of the drug was supposed to be retained or preferably enhanced. Therefore, we present an interdisciplinary comprehensive overview of interdisciplinary nature on nanopharmaceuticals based on doxorubicin and its nanoformulations with valuable information concerning trends, obstacles and prospective of nanopharmaceuticals development, mode of activity of sole drug doxorubicin and its nanoformulations based on different nanocarriers, their brief descriptions of biological activity through assessing in vitro and in vivo behavior.
Wang Y, Cuzzucoli F, Escobar A
… +3 more, Lu S, Liang L, Wang S
Nanotechnology
· 2018 Aug · PMID 29794338
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Cancer has become the most prevalent cause of deaths, placing a huge economic and healthcare burden worldwide. Nanoparticles (NPs), as a key component of nanomedicine, provide alternative options for promoting the effica...Cancer has become the most prevalent cause of deaths, placing a huge economic and healthcare burden worldwide. Nanoparticles (NPs), as a key component of nanomedicine, provide alternative options for promoting the efficacy of cancer therapy. Current conventional cancer models have limitations in predicting the effects of various cancer treatments. To overcome these limitations, biomimetic and novel 'tumor-on-a-chip' platforms have emerged with other innovative biomedical engineering methods that enable the evaluation of NP-based cancer therapy. In this review, we first describe cancer models for evaluation of NP-based cancer therapy techniques, and then present the latest advances in 'tumor-on-a-chip' platforms that can potentially facilitate clinical translation of NP-based cancer therapies.
Nanotechnology
· 2018 Aug · PMID 29756603
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Nanotechnology can produce materials with unique features compared to their bulk counterparts, which can be useful for medical applications (i.e. nanomedicine). Among the therapeutic agents used in nanomedicine, small mo...Nanotechnology can produce materials with unique features compared to their bulk counterparts, which can be useful for medical applications (i.e. nanomedicine). Among the therapeutic agents used in nanomedicine, small molecules or biomacromolecules, such as proteins or genetic materials, can be designed for disease diagnostics and treatment. To transport these biomacromolecules to the target cells, nanomedicine requires nanocarriers. Solid lipid nanoparticles (SLNs) are among the promising nanocarriers available, because they can be made from biocompatible materials and present high stability (over one year). In addition, upon the binding genetic material, SLNs form SLNplexes. However, little is yet known about how cells process these SLNplexes-in particular, how internalization and endosome acidification affects the transfection mediated by SLNplexes. Therefore, we aim to investigate how these processes affect SLNplex transfection in HEK293T cells. We find that the SLNplex is mainly internalized by clathrin-mediated endocytosis, which is a fast and reliable pathway to transfection, leading to approximately 60% transfection efficiency. Interestingly, upon acidification (below pH 5.0), the SLN seems to release its DNA content, which can be an essential step for SLNplex transfection. The underlying mechanisms described in this work may help improve SLNplex formulations and transfection efficiency. Moreover, these advances can improve the field of nanomedical research and bring new ways to cure diseases.
Terracciano M, Napolitano M, De Stefano L
… +2 more, De Luca AC, Rea I
Nanotechnology
· 2018 Jun · PMID 29553482
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Diatomite is a fossil material made of amorphous porous silica. In this work, polyethylene glycol (PEG)-modified diatomite NPs (PEG-DNPs) are decorated with gold NPs (AuNPs) by one-pot liquid-phase synthesis. Nanocomplex...Diatomite is a fossil material made of amorphous porous silica. In this work, polyethylene glycol (PEG)-modified diatomite NPs (PEG-DNPs) are decorated with gold NPs (AuNPs) by one-pot liquid-phase synthesis. Nanocomplexes (PEG-DNPs@AuNPs), with an average size of about 450 nm, are characterized by dynamic light scattering, electron microscopy, nitrogen adsorption/desorption analysis, UV-vis and photoluminescence spectroscopies. Preliminary studies on the use of the nanocomplex in nanomedicine are also presented. Tests performed incubating PEG-DNPs@AuNPs in physiological conditions reveal a good stability of material. Cellular uptake of labeled PEG-DNPs@AuNPs is investigated by confocal microscopy after incubation with human cervix epithelioid carcinoma (HeLa) cells up to 48 h: an efficient cytoplasmic localization is observed. In vitro cytotoxicity of nanocomplexes with a concentration up to 400 μg ml for 72 h is also evaluated. The results suggest the use of PEG-DNPs@AuNPs as advanced nanodevices adding imaging features to the nanocomplexes, due to AuNPs as contrast agent.
Yang X, Liu G, Shi Y
… +3 more, Huang W, Shao J, Dong X
Nanotechnology
· 2018 Jun · PMID 29504512
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Black phosphorus (BP), emerging as a new member of two-dimensional nanomaterials, has attracted growing research interests for its amazing photoelectric properties and promising application in electronic devices. Recentl...Black phosphorus (BP), emerging as a new member of two-dimensional nanomaterials, has attracted growing research interests for its amazing photoelectric properties and promising application in electronic devices. Recently, BP has been confirmed to be a desirable candidate for phototherapy against cancer, including photothermal therapy and photodynamic therapy. By regulating the number of layers, the bandgap of BP nanosheets (NSs) can be finely tuned to present near infrared light triggered phototherapeutic behaviors. Furthermore, the exfoliated nano-sized BP also exhibits excellent tumor-targeting property as a nanomedicine via the enhanced permeability and retention effect. With biodegradable nature and outstanding therapeutic performance, BP is highly expected to be developed as novel anti-cancer agents as well as a potential carrier for advanced cancer theranostics. In this review, on the basis of summarizing the recent advances of BP in biomedical applications, the size and layer effects of BP on its targeting effect and phototherapeutic performance are discussed. Then, the rationally designed multifunctional nanoplatforms based on BP are introduced. And, the remaining challenges and prospects of nano-BP for clinic applications against cancer are discussed and outlooked.
Nanotechnology
· 2018 Mar · PMID 29350186
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To reduce the side effects of chemotherapy and achieve effective and safe therapy for prostate cancer, herein a simple but multi-functional TiO:Gd@DOX/FA system activated by ultrasound was developed for the MRI-guided mu...To reduce the side effects of chemotherapy and achieve effective and safe therapy for prostate cancer, herein a simple but multi-functional TiO:Gd@DOX/FA system activated by ultrasound was developed for the MRI-guided multi-mechanism therapy of prostate cancer. TiO nanoparticles served as a sonosensitizer as well as a nanocarrier with the pH-responsive release of DOX. The doping of Gd was not only able to endow the TiO with magnetic resonance imaging (MRI) ability, but also further improve the sonodynamic ability of the TiO. The characterization of the as-prepared TiO:Gd@DOX/FA showed sensitive pH-responsive drug release, high reactive oxygen species (ROS) production, T -MRI contrast performance and excellent biocompatibility. The cytotoxicity assay in vitro showed cell death up to 91.68% after 48 h incubation induced by the TiO:Gd@DOX + ultrasound group. Meanwhile, in the in vivo synergistic therapy studies, the tumor sizes of all the nanomedicine groups were smaller than for the free DOX (V:V = 4.2). More importantly, the body showed nearly no weight loss. This safety was also confirmed by the H&E staining, biodistribution experiment and serum biochemistry results. Altogether, TiO:Gd@DOX/FA significantly reduced the side effects of DOX, augmented the levels of ROS and achieved effective and safe therapy, indicating its potential for the multi-mechanism therapy of prostate cancer.
Nanotechnology possesses the potential to revolutionize the diagnosis and treatment of tumors. The ideal nanoparticles used for in vivo cancer therapy should have long blood circulation times and active cancer targeting....Nanotechnology possesses the potential to revolutionize the diagnosis and treatment of tumors. The ideal nanoparticles used for in vivo cancer therapy should have long blood circulation times and active cancer targeting. Additionally, they should be harmless and invisible to the immune system. Here, we developed a biomimetic nanoplatform with the above properties for cancer therapy. Macrophage membranes were reconstructed into vesicles and then coated onto magnetic iron oxide nanoparticles (FeO NPs). Inherited from the FeO core and the macrophage membrane shell, the resulting FeO@MM NPs exhibited good biocompatibility, immune evasion, cancer targeting and light-to-heat conversion capabilities. Due to the favorable in vitro and in vivo properties, biomimetic FeO@MM NPs were further used for highly effective photothermal therapy of breast cancer in nude mice. Surface modification of synthetic nanomaterials with biomimetic cell membranes exemplifies a novel strategy for designing an ideal nanoplatform for translational medicine.
Ran X, Wang Z, Ju E
… +4 more, Pu F, Song Y, Ren J, Qu X
Nanotechnology
· 2018 Feb · PMID 29226844
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The logic device demultiplexer can convey a single input signal into one of multiple output channels. The choice of the output channel is controlled by a selector. Several molecules and biomolecules have been used to mim...The logic device demultiplexer can convey a single input signal into one of multiple output channels. The choice of the output channel is controlled by a selector. Several molecules and biomolecules have been used to mimic the function of a demultiplexer. However, the practical application of logic devices still remains a big challenge. Herein, we design and construct an intelligent 1:2 demultiplexer as a theranostic device based on azobenzene (azo)-modified and DNA/Ag cluster-gated nanovehicles. The configuration of azo and the conformation of the DNA ensemble can be regulated by light irradiation and pH, respectively. The demultiplexer which uses light as the input and acid as the selector can emit red fluorescence or a release drug under different conditions. Depending on different cells, the intelligent logic device can select the mode of cellular imaging in healthy cells or tumor therapy in tumor cells. The study incorporates the logic gate with the theranostic device, paving the way for tangible applications of logic gates in the future.
Kumar D, Mutreja I, Chitcholtan K
… +1 more, Sykes P
Nanotechnology
· 2017 Nov · PMID 29027909
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Nanomedicine has advanced the biomedical field with the availability of multifunctional nanoparticles (NPs) systems that can target a disease site enabling drug delivery and helping to monitor the disease. In this paper,...Nanomedicine has advanced the biomedical field with the availability of multifunctional nanoparticles (NPs) systems that can target a disease site enabling drug delivery and helping to monitor the disease. In this paper, we synthesised the gold nanoparticles (AuNPs) with an average size 18, 40, 60 and 80 nm, and studied the effect of nanoparticles size, concentration and incubation time on ovarian cancer cells namely, OVCAR5, OVCAR8, and SKOV3. The size measured by transmission electron microscopy images was slightly smaller than the hydrodynamic diameter; measured size by ImageJ as 14.55, 38.13, 56.88 and 78.56 nm. The cellular uptake was significantly controlled by the AuNPs size, concentration, and the cell type. The nanoparticles uptake increased with increasing concentration, and 18 and 80 nm AuNPs showed higher uptake ranging from 1.3 to 5.4 μg depending upon the concentration and cell type. The AuNPs were associated with a temporary reduction in metabolic activity, but metabolic activity remained more than 60% for all sample types; NPs significantly affected the cell proliferation activity in first 12 h. The increase in nanoparticle size and concentration induced the production of reactive oxygen species in 24 h.
Xie X, Gao G, Kang S
… +4 more, Lei Y, Pan Z, Shibayama T, Cai L
Nanotechnology
· 2017 Jun · PMID 28537226
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Being able to precisely control the morphologies of noble metallic nanostructures is of essential significance for promoting the surface-enhanced Raman scattering (SERS) effect. Herein, we demonstrate an overgrowth strat...Being able to precisely control the morphologies of noble metallic nanostructures is of essential significance for promoting the surface-enhanced Raman scattering (SERS) effect. Herein, we demonstrate an overgrowth strategy for synthesizing Au @ M (M = Au, Ag, Pd, Pt) core-shell heterogeneous nanocrystals with an orientated structural evolution and highly improved properties by using Au nanorods as seeds. With the same reaction condition system applied, we obtain four well-designed heterostructures with diverse shapes, including Au concave nanocuboids (Au CNs), Au @ Ag crystalizing face central cube nanopeanuts, Au @ Pd porous nanocuboids and Au @ Pt nanotrepangs. Subsequently, the exact overgrowth mechanism of the above heterostructural building blocks is further analysed via the systematic optimiziation of a series of fabrications. Remarkably, the well-defined Au CNs and Au @ Ag nanopeanuts both exhibit highly promoted SERS activity. We expect to be able to supply a facile strategy for the fabrication of multimetallic heterogeneous nanostructures, exploring the high SERS effect and catalytic activities.
Nanotechnology
· 2017 Jun · PMID 28368852
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The interest in nanodiamond applications in biology and medicine is on the rise over recent years. This is due to the unique combination of properties that nanodiamond provides. Small size (∼5 nm), low cost, scalable pro...The interest in nanodiamond applications in biology and medicine is on the rise over recent years. This is due to the unique combination of properties that nanodiamond provides. Small size (∼5 nm), low cost, scalable production, negligible toxicity, chemical inertness of diamond core and rich chemistry of nanodiamond surface, as well as bright and robust fluorescence resistant to photobleaching are the distinct parameters that render nanodiamond superior to any other nanomaterial when it comes to biomedical applications. The most exciting recent results have been related to the use of nanodiamonds for drug delivery and diagnostics-two components of a quickly growing area of biomedical research dubbed theranostics. However, nanodiamond offers much more in addition: it can be used to produce biodegradable bone surgery devices, tissue engineering scaffolds, kill drug resistant microbes, help us to fight viruses, and deliver genetic material into cell nucleus. All these exciting opportunities require an in-depth understanding of nanodiamond. This review covers the recent progress as well as general trends in biomedical applications of nanodiamond, and underlines the importance of purification, characterization, and rational modification of this nanomaterial when designing nanodiamond based theranostic platforms.
Cationic polymers as non-viral gene delivery carriers are widely used because of their strong condensing properties and long-term safety, but acute cytotoxicity is a persistent challenge. In this study, two types of poly...Cationic polymers as non-viral gene delivery carriers are widely used because of their strong condensing properties and long-term safety, but acute cytotoxicity is a persistent challenge. In this study, two types of polyplexes were prepared by co-formulating plasmid DNA and two cationic diblock copolymers PABOXA-b-PMOXA-PA (primary amine) and PABOXA-b-PMOXA-TA (tertiary amine) to check their transfection efficacies in HeLa cells and HEK293T cells, respectively. The plasmid DNA/PABOXA-b-PMOXA-PA polyplex showed higher transfection efficacy compared to the plasmid DNA/PABOXA-b-PMOXA-TA polyplex under an N/P ratio of 40. Both polymers exhibited low toxicity, attributed to the shielding effect of a hydrophilic, noncharged block. Mechanistic insight into differential transfection efficiencies of the polymers were gained by visualization and comparison of the condensates via transmission electron and atomic force microscopy. The results provide information suited for further structure optimization of polymers that are aimed for targeted gene delivery.
Handa T, Hirai T, Izumi N
… +6 more, Eto SI, Tsunoda SI, Nagano K, Higashisaka K, Yoshioka Y, Tsutsumi Y
Nanotechnology
· 2017 Mar · PMID 28240988
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Many of the beneficial and toxic biological effects of nanoparticles have been shown to have a negative correlation with particle size. However, few studies have demonstrated biological effects that only occur at specifi...Many of the beneficial and toxic biological effects of nanoparticles have been shown to have a negative correlation with particle size. However, few studies have demonstrated biological effects that only occur at specific nanoparticle sizes. Further elucidation of the size-specific biological effects of nanoparticles may reveal not only unknown toxicities, but also novel benefits of nanoparticles. We used surface-unmodified silica particles with a wide range of diameters and narrow size intervals between the diameters (10, 30, 50, 70, 100, 300, and 1000 nm) to investigate the relationship between particle size and acute toxicity after intravenous administration in mice. Negative correlations between particle size and thrombocytopenia, liver damage, and lethal toxicity were observed. However, a specific size-effect was observed for the severity of hypothermia, where silica nanoparticles with a diameter of 50 nm induced the most severe hypothermia. Further investigation revealed that this hypothermia was mediated not by histamine, but by platelet-activating factor, and it was independent of the thrombocytopenia and the liver damage. In addition, macrophages/Kupffer cells and platelets, but not neutrophils, play a critical role in the hypothermia. The present results reveal that silica nanoparticles have particle size-specific toxicity in mice, suggesting that other types of nanoparticles may also have biological effects that only manifest at specific particle sizes. Further study of the size-specific effects of nanoparticles is essential for safer and more effective nanomedicines.
Nanotechnology
· 2017 Mar · PMID 28177935
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Silicon nanoparticles (SiNPs) prepared by mechanical grinding of luminescent porous silicon were coated with a biopolymer (dextran) and investigated as a potential theranostic agent for bioimaging and sonodynamic therapy...Silicon nanoparticles (SiNPs) prepared by mechanical grinding of luminescent porous silicon were coated with a biopolymer (dextran) and investigated as a potential theranostic agent for bioimaging and sonodynamic therapy. Transmission electron microscopy, photoluminescence and Raman scattering measurements of dextran-coated SiNPs gave evidence of their enhanced stability in water. In vitro experiments confirmed the lower cytotoxicity of the dextran-coated NPs in comparison with uncoated ones, especially for high concentrations of about 2 mg ml. Efficient uptake of the NPs by cancer cells was found using bioimaging in the optical transmittance and photoluminescence modes. Treatment of the cells with uptaken SiNPs by therapeutic ultrasound for 5-20 min resulted in a strong decrease in the number of living cells, while the total number of cells remained nearly unchanged. The obtained data indicate a 'mild' effect of the combined action of ultrasonic irradiation and SiNPs on cancer cells. The observed results reveal new opportunities for controlling the photoluminescent and sonosensitizing properties of silicon-based NPs for applications in the diagnostics and mild therapy of cancer.