Mesoporous silica nanoparticles (MSNs) have a network of pores that give rise to extremely high specific surface areas, making them attractive materials for applications such as adsorption and drug delivery. The pore topology can be readily tuned to achieve a variety of structures such as the hexagonally ordered Mobil Crystalline Material 41 (MCM-41) and the disordered “wormhole” (WO) mesoporous silica (MS) structure. In this work, the effects of pore topology and iron oxide core on doxorubicin loading and release were investigated using MSNs with pore diameters of approximately 3 nm and sub-100 nm particle diameters. The nanoparticles were loaded with doxorubicin, and the drug release into phosphate-buffered saline (PBS, 10 mM, pH 7.4) at 37 °C was monitored by fluorescence spectroscopy. The release profiles were fit using the Peppas model. The results indicated diffusion-controlled release for all samples. Statistically significant differences were observed in the kinetic host–guest parameters for each sample due to the different pore topologies and the inclusion of an iron oxide core. Applying a static magnetic field to the iron oxide core WO-MS shell materials did not have a significant impact on the doxorubicin release. This is the first time that the effects of pore topology and iron oxide core have been isolated from pore diameter and particle size for these materials.
Hepatocellular carcinoma (HCC) is the most common form of liver cancer, occurring primarily in regions where viral hepatitis infections are common. Unfortunately, most HCC cases remain undiagnosed until late stages of the disease when patient outcome is poor, typically limiting survival from a few months to a year after initial diagnosis. In order to better care for HCC patients, new target-specific approaches are needed to improve early detection and therapeutic intervention. In this work, polymeric nanoparticles functionalized with a HCC-specific aptamer were examined as potential targeted drug delivery vehicles. Specifically, doxorubicin-loaded nanoparticles were prepared via nanoprecipitation of blends of poly(lactic-co-glycolic acid)-b-poly(ethylene glycol). These particles were further functionalized with the HCC-specific TLS11a aptamer. The in vitro interaction and therapeutic efficacy of the aptamer and aptamer-functionalized nanoparticles were characterized in a hepatoma cell line. Nanoparticles were found to be spherical in shape, roughly 100–125 nm in diameter, with a low polydispersity (≤0.2) and slightly negative surface potential. Doxorubicin was encapsulated within the particles at ~40 % efficiency. Drug release was found to occur through anomalous transport influenced by diffusion and polymer relaxation, releasing ~50 % doxorubicin in the first 10 h and full release occurring within 36 h. Confocal microscopy confirmed binding and attachment of aptamer-targeted nanoparticles to the cell surface of cultured HCC cells. Efficacy studies demonstrated a significant improvement in doxorubicin delivery and cell-killing capacity using the aptamer-functionalized, drug-loaded nanoparticles versus controls further supporting use of aptamer nanoparticles as a targeted drug delivery system for HCC tumors.
Graphical abstract In this work, polymeric nanoparticles functionalized with a liver cancer-specific aptamer were examined as potential targeted drug delivery vehicles. The aptamer-functionalized nanoparticles were found to significantly improve doxorubicin drug delivery and cell-killing capacity in vitro versus non-targeted controls, supporting their use as a targeted treatment toward liver cancer tumors.
Barium titanate (BT) nanoparticles are coated by titania and modified by fluoroalkylsilane. The BT nanoparticles are incorporated into polyvinylidene fluoride (PVDF) films to obtain highly dielectric and transparent nanocomposite films at low filler loadings. Incorporation of BT nanoparticles having average sizes of 12 and 22 nm is performed. Incorporation of BT nanoparticles enhances the permittivity of PVDF films. Higher transparency of nanocomposite films is achieved by incorporating 12-nm nanoparticles compared to that by 22-nm nanoparticles. The polarisation mechanism in the nanocomposite films is examined using the Vo–Shi model. The result indicates that even a slight increase in the thickness of titania-coating layer on the BT nanoparticles increase the permittivity of the nanocomposite films. Comparison of the measured and calculated permittivities showed that the incorporation of BT nanoparticles coated with titania provides a practical approach to create transparent nanocomposite films having high permittivity.
A protocol is described for an efficient transamidation of amides with amines in the presence of mesoporous silica nanoparticles (MSNs). The latter is used as a green, heterogeneous, and recyclable nanocatalyst, under solvent-free conditions. Following this protocol, a wide range of aromatic, aliphatic, and cyclic/acyclic primary or secondary amines are used in synthesis of a series of amides with good to excellent yields (65–96%). MSNs is characterized by using scanning electron microscopy (SEM), transmission electron microscopy (TEM), small-angle powder X-ray diffraction (XRD), nitrogen adsorption-desorption analysis, and FT-IR spectroscopy. The metal/solvent-free condition, easy work up, high purity of the products, recyclability, and environmentally-friendly nature of the catalyst are the attractive features of this methodology.
Graphical abstract An efficient transamidation of carboxamides was achieved via the use of mesoporous nanoparticles as green nanocatalyst. The metal/solvent-free condition, easy work up, high purity of the products, recyclability, and environmentally-friendly nature of the catalyst are the attractive features of this methodology.
Recently, targeted drug delivery systems (TDDS) have offered a great potential and benefits towards the anti-tumor drug delivery. In this work, we designed the TDDS using a biocompatible poly(ethylene glycol)-poly(β-amino esters) amphiphilic block copolymer (PEG-PAEs) synthesized by Michael addition polymerization for combinatorial therapy. Further, the chemotherapeutic agents’ doxorubicin (DOX) and AS1411 DNA aptamer (Apt) are encapsulated in the PEG-PAEs NPs (PDANs) for co-delivery therapeutics. PDANs have shown the monodisperse spherical shape, smooth surface with a net positive charge (average diameter—183.1 ± 27.2 nm, zeta potential—31.2 ± 6.3 mV), and good colloidal stability (critical micelle concentration of PEG-PAEs is about 6.3 μg/mL). The pH-sensitive PAEs endowed PDANs both pH-triggered drug release characteristics and enhanced endo/lysosomal escape ability, thus improving the localization and cytotoxicity of DOX. AS1411 Apt conjugated PDANs precisely targeted nucleolin and their uptake correlates to a significant activity enhancement only in tumor cells (MCF-7) but not in normal cells (MCF-10A). Thus, PDANs can be a very promising targeted drug delivery platform for effective breast cancer therapy.
Despite advancements in treatment of infectious diseases, opportunistic pathogens continue to pose a worldwide threat. Identifying a source of infection/inflammation is often challenging which highlights the need of improved diagnostic agents. Using a model of local S. aureus infection, here we evaluated the potential of betamethasone or dexamethasone loaded in poly (lactic acid) nanoparticles and radiolabeled with 99mTc to detect an infection/inflammation site in vivo. A betamethasone and dexamethasone nanoparticles (NPs) with 200 and 220 nm in size, respectively, were created with a 98% 99mTc radiolabeling efficiency. When injected in infected mice, betamethasone NPs presented a higher accumulation in the infected hind paw in comparison with dexamethasone NPs. Our results suggest that this nanosystem may be a valid nanoradiopharmaceutical for the detection of inflammation/infection foci in vivo.
A simple solid-state method has been applied to synthesize Ni/reduced graphene oxide (Ni/rGO) nanocomposite under ambient condition. Ni nanoparticles with size of 10–30 nm supported on reduced graphene oxide (rGO) nanosheets are obtained through one-pot solid-state co-reduction among nickel chloride, graphene oxide, and sodium borohydride. The Ni/rGO nanohybrid shows enhanced catalytic activity toward the reduction of p-nitrophenol (PNP) into p-aminophenol compared with Ni nanoparticles. The results of kinetic research display that the pseudo-first-order rate constant for hydrogenation reaction of PNP with Ni/rGO nanocomposite is 7.66 × 10?3 s?1, which is higher than that of Ni nanoparticles (4.48 × 10?3 s?1). It also presents superior turnover frequency (TOF, 5.36 h?1) and lower activation energy (Ea, 29.65 kJ mol?1) in the hydrogenation of PNP with Ni/rGO nanocomposite. Furthermore, composite catalyst can be magnetically separated and reused for five cycles. The large surface area and high electron transfer property of rGO support are beneficial for good catalytic performance of Ni/rGO nanocomposite. Our study demonstrates a simple approach to fabricate metal-rGO heterogeneous nanostructures with advanced functions.
It is well known that when nanoparticles (NPs) are exposed to biological fluid, it results into formation of nanoparticle protein corona, which has been the subject of extensive studies for the development of targeted drug delivery. In this work, we demonstrated the dynamic light scattering, fluorescence, and UV-visible spectroscopy as quantitative and qualitative tools to monitor adsorption of BSA protein onto silver nanoparticles (AgNPs). The adsorption resulted in significant gradual increase in average hydrodynamic radius of BSA-AgNP corona from 24 to 35 nm and its attainment of equilibrium point (saturation) that correlated with albumin concentration enables condition for bound and unbound protein adsorption to be interpreted. Using DLS, the dissociation constant (KD) was obtained for soft corona to be 2.09?±?0.30 μM. The UV-visible and fluorescence spectroscopy results were correlated with DLS. Loss of percent helicity in secondary structure of adsorbed BSA was monitored in both coronas as compared to native protein. Both coronas were found to be biocompatible with RBC membrane. Further, the results of adsorption isotherm model were used to validate the multilayer formation of albumin protein on silver nanoparticles. The obtained results would be relevant in the drug design development for tumor-targeted therapy.
Dendritic Pt–Cu nanoparticles were synthesized by a facile one-step method with the help of surfactant Brij58 at room temperature, and we also studied the effects of different Pt–Cu ratios on the morphology and size of nanoparticles. In addition, we further tuned the morphology of the Pt–Cu nanostructures by introducing bromide ions, eventually leading to the appearance of some tripod-like structures. Compared with dendritic Pt–Cu and commercial Pt black, these tripod-like Pt–Cu nanostructures exhibited higher electrocatalytic activity and CO tolerance for catalyzing methanol oxidation.
Porous polyacrylamide hydrogel (PAM) was prepared by polymerization at room temperature. Cadmium sulfide/polyacrylamide hydrogels (CdS/PAM) was synthesized by in situ loading CdS nanoparticles and used for photocatalytic decomposition of water for the first time. The size distribution of the loaded CdS nanoparticles is 3–12 nm. We studied the enhanced photocatalytic activity and photo-corrosion inhibition of CdS/PAM the compared with pure CdS and probed the mechanism of the improvement. In particular, the CdS/PAM prepared in 0.003 M CdCl2 solution exhibited the highest hydrogen production efficiency of 2.929 mmol g?1 h?1, about 79 times that of pure CdS. The results demonstrate that the formation of new N–Cd bond and high transmittance of CdS/PAM dramatically enhance photocatalytic activity. The electron cloud of nitrogen atom can attract holes and repel photogenerated electrons, which lowers the carrier recombination probability. The results also reveal that the excellent hydrophilicity of hydrogel plays an important role in the inhibition of photocorrosion. In addition, CdS/PAM is easily recycled and processed. The present work will pave a good way for the application of smart hydrogels in the field of photocatalytic hydrogen production.
Carbon-based nanoparticles (NPs) such as fullerenes and nanotubes have been extensively studied for drug delivery in recent years. The permeation process of fullerene and its derivative molecules through membrane is essential to the utilization of fullerene-based drug delivery system, but the mechanism and the dynamics of permeation through cell membrane are still unclear. In this study, coarse-grained molecular dynamics simulations were performed to investigate the permeation process of functionalized fullerene molecules (ca. 0.72 nm) through the membrane. Our results show that single functionalized fullerene molecule in such nanoscale could permeate the lipid membrane in micro-second time scale. Pristine C60 molecules prefer to aggregate into several small clusters while C60OH15 molecules could aggregate into one big cluster to permeate through the lipid membrane. After permeation of C60 or its derivatives into membrane, all C60 and C60OH15 molecules disaggregated and monodispersed in the lipid membrane.
Nitrilimine cycloadditions to ethylenes, acetylenes, and activated nitriles have been exploited in the presence of catalytic amounts of oleic-acid-coated iron oxide nanoparticles (diameter?=?11.9?±?1.0 nm). The reactions were fully regioselective with monosubstituted ethylenes and ethyl cyanoformiate, while mixtures of cycloadducts were obtained in the presence of methyl propiolate. The intervention of iron oxide nanoparticles allowed carrying out the cycloadditions at milder conditions compared to the metal-free thermal processes. A labile intermediate has been proposed to explain this behavior.
Graphical abstract Nitrilimine cycloadditions to ethylenes, acetylenes, and activated nitriles have been exploited in the presence of catalytic amounts of oleic-acid-coated iron oxide nanoparticles.
The new vessel formations play a vital role in growth and spread of cancer. Current anti-angiogenic therapies, predominantly based on vascular endothelial growth factor (VEGF) inhibition, can inhibit vascular development; however, they are usually ineffective against the primary tumor occurrence. The aim of this study was to assess anti-angiogenic effects of gold nanoparticles (AuNPs) functionalized with Semaphorin (Sema) 3F protein. The polyethylene glycol (PEG)-coated AuNPs were covalently functionalized with Sema 3F and labeled with the TAMRA fluorescent dye. The effect of the NPs on human umbilical vein endothelial cells (HUVECs) is probed in the way of internalization and viability assays. AuNP-Sema 3F bioconjugates showed great endothelial cell uptake. AuNP-Sema 3F bioconjugates reduced VEGF165-induced endothelial cell proliferation more effectively than Sema 3F alone, suggesting that the therapeutic effects of Sema 3F can be improved by conjugation to AuNPs. Also, no significant toxicity effect was induced by bioconjugates. This is the first study that reports a covalent binding of full length Sema 3F to NPs. The exogenously administration of Sema 3F, which has both anti-angiogenic and anti-tumoral activity, to tumor vasculature via a carrying platform may not only lead to more effective anti-angiogenic treatment but also may make current approach more applicable in clinical use like drug delivery system.
In the past decade, a variety of drug carriers based on mesoporous silica nanoparticles has been extensively reported. However, their biocompatibility still remains debatable, which motivated us to explore the porous nanostructures of other metal oxides, for example titanium dioxide (TiO2), as potential drug delivery vehicles. Herein, we report the in vitro hemolysis, cytotoxicity, and protein binding of TiO2 nanoparticles, synthesized by a sol–gel method. The surface of the TiO2 nanoparticles was modified with hydroxyl, amine, or thiol containing moieties to examine the influence of surface functional groups on the toxicity and protein binding aspects of the nanoparticles. Our study revealed the superior hemocompatibility of pristine, as well as functionalized TiO2 nanoparticles, compared to that of mesoporous silica, the present gold standard. Among the functional groups studied, aminosilane moieties on the TiO2 surface substantially reduced the degree of hemolysis (down to 5%). Further, cytotoxicity studies by MTT assay suggested that surface functional moieties play a crucial role in determining the biocompatibility of the nanoparticles. The presence of NH2– functional groups on the TiO2 nanoparticle surface enhanced the cell viability by almost 28% as compared to its native counterpart (at 100 μg/ml), which was in agreement with the hemolysis assay. Finally, nonspecific protein adsorption on functionalized TiO2 surfaces was examined using human serum albumin and it was found that negatively charged surface moieties, like –OH and –SH, could mitigate protein adsorption to a significant extent.
Zein nanoparticles covalently linked to folic acid were hypothesized to sustain the release of the folic acid in addition to targeting cancer cells overexpressing folate-binding receptors, whereas zein nanoparticles with physically entrapped folic acid would only be able to control the release of the bioactive without targeting of cancer cells. The two types of particles, folic acid covalently linked zein nanoparticles (ZN-FA nps) and zein nanoparticles with entrapped folic acid (ZN(FA) nps), were synthesized and the covalent link between folic acid and zein was assessed by Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance spectroscopy (1H NMR). Their size, polydispersity index, zeta potential, morphology, and loading capacity were evaluated by dynamic light scattering (DLS), transmission electron microscopy (TEM), and spectrophotometric technique. The release studies of the folic acid preformed in phosphate-buffered saline (PBS) at 37 °C for 7 days concluded that the release of the loaded folic acid was sustained over 7 days for both systems. The cytotoxicity was investigated using a methyl thiazolyl tetrazolium (MTT) assay, and the results showed that zein nanoparticles were biocompatible to HeLa (an overexpressing folate receptor cells) and A549 (a deficient folate receptor cells) cells, which have different levels of folate receptors on surface and both folic acid nanoparticle systems were able to diminish the adverse toxic effect of folic acid to cells. The increased uptake of ZN-FA nps relative to ZN(FA) nps supported the use of ZN-FA nps as targeting nanoagents to cells overexpressing folate receptors.
This work presents the synthesis of magnetite nanoparticle (MNP) coated with poly(N,N-diethylaminoethyl methacrylate)-b-poly(N-isopropyl acrylamide-st-thiolactone acrylamide) (PDEAEMA-b-P(NIPAAm-st-TlaAm) copolymer and its use in controlled drug release and bio-conjugation. TlaAm units in the copolymer were ring-opened with various alkyl amines to form thiol groups (-SH), followed by thiol-ene coupling reactions with acrylamide-coated MNP and then quaternized to obtain cationic copolymer-MNP assemblies (the size <?200 nm/cluster). The use of alkyl amines having various chain lengths (e.g., 1-propylamine, 1-octylamine, or 1-dodecylamine) in the nucleophilic ring-opening reactions of the thiolactone rings affected their magnetic separation ability, water dispersibility, and release rate of doxorubicin model drug. In all cases, when increasing the temperature, they showed a thermo-responsive behavior as indicated by the decrease in hydrodynamic size and the accelerated drug release rate. These copolymer-MNP assemblies could be used as a novel platform with thermal-triggering controlled drug release and capability for adsorption with any negatively charged biomolecules.
Single-walled carbon nanotubes (SWNTs) are 1D nanostructures with distinct physical and chemical properties that have shown great promise for applications in many fields, including biomedicine. Since for biomedical application the water solubility is crucial and SWNTs have low solubility, various methods (including polymer and biopolymer wrapping, chemical modifications) have been developed to solubilize and disperse them in water. Due to their unique optical properties such as photoluminescence in the NIR and strong resonant Raman signatures, they can be used as nanoprobes in biomedical imaging and phototherapies. Furthermore, decoration of SWNTs with noble metal nanoparticles will induce an excellent surface-enhanced Raman scattering (SERS) effect of the nanoparticles-SWNTs composites, with applications in cell imaging. Herein, we present a new and facile strategy for the DNA-assisted decoration of SWNTs with gold nanoparticles (AuNPs) and their application in SERS imaging. By ultrasonication at room temperature of SWNTs with AuNPs functionalized with synthetic DNA, SWNT-AuNPs nanocomposites with enhanced Raman signal were obtained. Among the important advantages of the proposed method are the presence of the free DNA overhangs around the SWNT-AuNPs suitable for post-synthetic modification of nanocomposite through hybridization of complementary DNA strands containing molecules of interest attached by well-developed bio-conjugation chemistry.
Amphiphilic gold nanoparticles (AuNPs) functionalized with mixed monolayers consisting of hydrophobic and hydrophilic ligands find widespread applications in biosensing, drug delivery, and bioimaging. One important aspect of amphiphilic AuNPs in such applications is the tuning of the surface properties of these AuNPs by modifying the composition of the ligands. In this study, well-dispersed AuNPs as individuals with mixed monolayers of hydrophobic and hydrophilic ligands were synthesized and the ratios of hydrophilic and hydrophobic ligands on the AuNP surfaces with varying ligand lengths were investigated by electrostatic titration. We demonstrated that longer hydrophobic ligands have higher affinity for the AuNP surface, and that the relative ligand length plays an important role in determining the maximum hydrophobic coverage on the AuNP surface at which the ratio of the amount of hydrophobic to that of hydrophilic ligands on the AuNP surface is the largest, for AuNPs to remain as individuals. We expect that the AuNPs synthesized with diverse ratios of hydrophobic and hydrophilic ligands on the surface can be useful in biological applications.
In this study, a tumor-targeting poly(d, l-lactic-co-glycolic acid) (PLGA) loaded “off-on” fluorescent probe nanoparticle (PFN) delivery system was developed to evaluate the region of tumor by off-on fluorescence. The biodegradability of the nanosize PFN delivery system readily released the probe under tumor acidic conditions. The probe with good biocompatibility was used to monitor the intracellular glutathione (GSH) of cancer cells and selectively localize to mitochondria for tumor imaging. The incorporated tumor-targeting probe was based on the molecular photoinduced electron transfer (PET) mechanism preventing fluorescence (“off” state) and could be easily released under tumor acidic conditions. However, the released tumor-targeting fluorescence probe molecule was selective towards GSH with high selectivity and an ultra-sensitivity for the mitochondria of cancer cells and tissues significantly increasing the probe molecule fluorescence signal (“on” state). The tumor-targeting fluorescence probe showed sensitivity to GSH avoiding interference from cysteine and homocysteine. The PFNs could enable fluorescence-guided cancer imaging during cancer therapy. This work may expand the biological applications of PFNs as a diagnostic reagent, which will be beneficial for fundamental research in tumor imaging.
Graphical abstract The tumor-bearing mice were injected intravenously through the tail with the PFNs; after injection, the PFNs can accumulate to tumor region via the EPR effect. The PFNs can prolong blood circulation time and easily degraded under tumor acidic conditions to release an off-on probe in tumor, and the probe can target glutathione of mitochondria, making probe fluorescence enhanced largely (“on” state).
A novel core–shell nanocomposite Ni–Ca@mSiO2 was first prepared by a modified Stöber method in this paper. It has a core–shell structure with Ni (about 8 nm in diameter) and Ca as the cores and mesoporous silica as the outer shell, as proven by the transmission electron microscopy. This nanocomposite exhibited good catalytic performance in the selective hydrogenation of benzophenone, with 96.1% conversion and 94.9% selectivity for benzhydrol under relatively mild reaction conditions. It was demonstrated that addition of small amounts of alkaline Ca can not only markedly improve the dispersion of the active species but also tune the acid–base property of this nanocomposite, resulting in the efficient suppression of benzhydrol dehydration to achieve a high selectivity. Furthermore, the core–shell nanocomposite Ni–Ca@mSiO2 can be recycled four runs without appreciable loss of its initial activity, more stable than the traditional supported nanocatalyst Ni–Ca/mSiO2. It was suggested that the outer mesoporous silica shell of Ni–Ca@mSiO2 can prevent both the aggregation and the leaching of the active Ni species, accounting for its relatively good stability.
Graphical abstract A magnetic core–shell nanocomposite Ni–Ca@mSiO2 exhibited good activity, selectivity, and reusability in benzophenone selective hydrogenation.
