Magnetic iron oxide nanoparticle-hollow mesoporous silica Spheres:Fabrication and potential application in drug delivery

A facile method is developed for the fabrication of magnetic iron oxide nanoparticle-hollow mesoporous silica spheres (IONP-HMSs) and explored their potential application in drug delivery. Through the self-assembling process of IONPs and the formation of mesoporous silica shells, the IONP-HMSs with hollow interior cavity were obtained. The cetyltrimethyl ammonium bromide (CTAB) encapsulated IONP-containing spheres served as the template to establish the mesoporous silica shells. Typical anti-cancer drug, doxorubicin hydrochloride (DOX) was applied for drug loading and release process of IONP-HMSs, which demonstrated the IONP-HMSs have a high drug loading efficiency and allow pH-trigged release of DOX in vitro. Moreover, the IONP-HMSs exhibited excellent biocompatibility and enhanced DOX therapeutic efficacy to HeLa cells. Compared with traditional methods, the reported microemulsion-based method for the synthesis of IONP-HMSs enables the formation of hollow-structured nanocomposite without any complex template-removing process, which could pave the way to improving the therapeutic efficacy in drug delivery system.     

Adsorptive removal of congo red dye from aqueous solution using bael shell carbon

This study investigates the potential use of bael shell carbon (BSC) as an adsorbent for the removal of congo red (CR) dye from aqueous solution. The effect of various operational parameters such as contact time, temperature, pH, and dye concentration were studied. The adsorption kinetics was modeled by first-order reversible kinetics, pseudo-first-order kinetics, and pseudo-second-order kinetics. The dye uptake process obeyed the pseudo-second-order kinetic expression at pH 5.7, 7 and 8 whereas the pseudo-first-order kinetic model was fitted well at pH 9. Langmuir, Freundlich and Temkin adsorption models were applied to fit adsorption equilibrium data. The best-fitted data was obtained with the Freundlich model. Thermodynamic study showed that adsorption of CR onto BSC was endothermic in nature and favorable with the positive ΔH° value of 13.613 kJ/mol.     

Encapsulating doxorubicin-intercalated lamellar nanohydroxyapatite into PLGA nanofibers for sustained drug release

In this work, doxorubicin (DOX) was intercalated into layered nanohydroxyapatite (LHAp). The drug loaded LHAp (DOX@LHAp) was then mixed with poly(lactic-co-glycolic acid) (PLGA) and electrospun to yield DOX@LHAp/PLGA composite scaffolds. As control, needle-like nanohydroxyapatite (nHAp) was also used to make an DOX@nHAp/PLGA composite scaffold and bare DOX was used to fabricate DOX/PLGA scaffold. The morphology, release behavior of DOX, and capability to inhibit cancer cells were assessed. The addition of DOX-loaded nHAp to PLGA causes a slight decrease in the average fiber diameter of DOX@LHAp/PLGA as compared to PLGA. The in vitro drug release tests reveal a much faster release of DOX from DOX/PLGA than DOX@LHAp/PLGA. Moreover, DOX@LHAp/PLGA displays a more sustainable release over DOX@nHAp/PLGA due to the storage of DOX in the gallery of LHAp, which is further proved by their cancer cell inhibition results. We believe that the DOX@LHAp/PLGA scaffold has potential as an implantable drug delivery system.     

Low‐Magnetization Magnetic Microcapsules: A Synergistic Theranostic Platform for Remote Cancer Cells Therapy and Imaging

Multifunctional magnetic microcapsules (MMCs) for the combined cancer cells hyperthermia and chemotherapy in addition to MR imaging are successfully developed. A classical layer‐by‐layer technique of oppositely charged polyelectrolytes (poly(allylamine hydrochloride) (PAH) and poly(4‐styrene sulfonate sodium) (PSS)) is used as it affords great controllability over the preparation together with enhanced loading of the chemotherapeutic drug (doxorubicin, DOX) in the microcapsules. Superparamagnetic iron oxide (SPIOs) nanoparticles are layered in the system to afford MMC1 (one SPIOs layer) and MMC2 (two SPIOs layers). Most interestingly, MMC1 and MMC2 show efficient hyperthermia cell death and controlled DOX release although their magnetic saturation value falls below 2.5 emu g^?1, which is lower than the 7–22 emu g^?1 reported to be the minimum value needed for biomedical applications. Moreover, MMCs are pH responsive where a pH 5.5 (often reported for cancer cells) combined with hyperthermia increases DOX release predictably. Both systems prove viable when used as T2 contrast agents for MR imaging in HeLa cells with high biocompatibility. Thus, MMCs hold a great promise to be used commercially as a theranostic platform as they are controllably prepared, reproducibly enhanced, and serve as drug delivery, hyperthermia, and MRI contrast agents at the same time.     

具有双重治疗机制的磁性纳米无定型氧化铁基药物递送系统

合成一种具有pH响应性的聚乙二醇(PEG)修饰无定形介孔氧化铁纳米粒子(AFe-PEG). 这种纳米粒子可以高效负载药物分子如阿霉素(DOX),构成新型多功能AFe-PEG/DOX药物递送体系. DOX的负载率高达948 mg/g-纳米粒子. 在酸性溶液中,AFe-PEG/DOX纳米粒子不仅可以有效释放DOX,同时可以释放Fe离子进行Fenton反应,将H₂O₂转变成·OH自由基. 体外实验结果表明,AFe-PEG/DOX纳米粒子对HeLa细胞同时具有化疗和化学动力学疗法的疗效. 同时,由于AFe-PEG/DOX 纳米粒子本身的磁性,使其在外部磁场中的细胞内化效率也得到了提高.     

A new empirical rate equation for adsorption kinetics at solid/solution interface

It has been shown that most of the previously reported empirical rate equations for kinetics of adsorption at the solid/solution interface show high relative errors at the initial times of adsorption. In the present work we made a modification onto pseudo-first-order and pseudo-second-order models and presented a new empirical rate equation, called the modified pseudo-n-order (MPnO) model. The results of fitting to the experimental data show that the MPnO model has low relative errors in the whole range of adsorption time.     

三维拉曼成像技术用于纳米金刚石与细胞相互作用过程的研究

纳米金刚石(NDs),作为一种具备良好生物兼容性、化学稳定性、药物负载能力和众多不可比拟优越性能的材料,其在生物医学领域的应用被广泛关注,尤其是在生物成像和抗癌药物传输领域。首先对不同尺寸纳米金刚石的拉曼性能进行评价,确定了100 nm高温高压合成的NDs更适宜作为拉曼生物探针。之后,为了生物领域的应用,这些NDs表面的杂质经过羧基化方式处理获得均一表面性能,并采用扫描电镜、红外、拉曼和粒径分析手段对该过程进行验证。然后,NDs作为拉曼探针被用于快速定位HeLa细胞内NDs的分布,验证了HepG2细胞对NDs内吞过程的时间依赖性。此外,借助非侵入性的三维(3D)共聚焦拉曼成像技术,可视化观察了四种不同细胞(HeLa, HepG2, C6和MDCK)对NDs内吞量和滞留量的差异。其中,MDCK这种正常细胞内部极少发现NDs,而其他三种癌细胞中有大量NDs信号,显示出不同种类细胞对于NDs的吞入和滞留量的明显差异。实验结果表明,纳米金刚石拉曼生物探针不仅可以用于生物成像,更为癌症的定位和诊断提供可能性。     

Quantum Chemical Study on the adsorption of metformin drug on the surface of pristine,Si- and Al-doped (5, 5) SWCNTs

Adsorption properties of metformin (MF) drug onto pristine, Si- and Al-doped (5, 5) armchair single-wall carbon nanotubes (SWCNTs) were studied using density functional theory (DFT) calculations at the B3LYP and ωB97XD methods with the standard 6–311 G** basis set. The most stable geometries of the MF drug molecule onto pristine, Si- and Al-doped (5, 5) CNTs were selected and evaluated in the gaseous and aqueous environments. We calculated the natural bond orbitals (NBO), Frontier molecular orbital (FMO), density of states (DOS) and molecular electrostatic potential (MEP) of systems upon adsorption of MF drug. It was found that the reaction of MF drug with pure SWCNT is physisorption in nature, while high chemisorption can be achieved by using Al- and Si-doped SWCNTs. Despite Al-doped SWCNT provides stronger adsorption, however the change in the energy gap of Si-doped SWCNT is more pronounced. It is predicted that MF drug incorporating Si-doped SWCNT can be extended as drug delivery system.     

Memory effect of pentacene field-effect transistors with embedded monolayer of semiconductor colloidal nano-dots

We demonstrate memory effect of pentacene-based field-effect transistors (FETs) in which CdSe/ZnS colloidal nano-dots (NDs) are embedded. The colloidal NDs were dispersed in chloroform, and spread over a water surface to form monolayer of NDs. Then, they were transferred onto a 30-nm-thick poly(methyl methacrylate) (PMMA) surface by horizontal lifting method, and a 30-nm-thick pentacene film was deposited as an active layer to fabricate FETs. The threshold voltage (V_th) was shifted by ∼10 V after a writing voltage of 70–100 V was applied to the gate electrode of the memory-FETs. On the other hand, such a large shift of V_th was not observed for reference pentacene-FETs without NDs. We consider that the large shift of V_th is due to electrons trapped in the NDs at the interface of pentacene and PMMA layers.     

Electrostatically mediated adsorption by nanodiamond and nanocarbon particles

Nanodiamond (ND) and other nanocarbon particles are popular platforms for the immobilization of molecular species. In the present research, factors affecting adsorption and desorption of propidium iodide (PI) dye, chosen as a charged molecule model, on ND and sp ² carbon nanoparticles were studied, with a size ranging from 75 to 4,305 nm. It was found that adsorption of PI molecules, as characterized by ultraviolet–visible spectroscopy, on ND particles is strongly influenced by sorbent-sorbate electrostatic interactions. Different types of NDs with a negative zeta potential were found to adsorb positively charged PI molecules, while no PI adsorption was observed for NDs with a positive zeta potential. The type and density of surface groups of negatively charged NDs greatly influenced the degree and capacity of the PI adsorbed. Ozone-purified NDs had the highest capacity for PI adsorption, due to its greater density of oxygen containing groups, i.e., acid anhydrides and carboxyls, as assessed by TDMS and TOF–SIMS. Single wall nanohorns and carbon onion particles were found to adsorb PI regardless of their zeta potential; this is likely due to π bonding between the aromatic rings of PI and the graphitic surface of the materials and the internal cavity of the horns.     

Kinetics and thermodynamics of Pb(II) adsorption onto modified spent grain from aqueous solutions

Spent grain, a main by-product of the brewing industry, is available in large quantities, but its main application has been limited to animal feeding. Nevertheless, in this study, spent grain modified with 1 M NaCl solution as a novel adsorbent has been used for the adsorption of Pb(II) in aqueous solutions. Isotherms, kinetics and thermodynamics of Pb(II) adsorption onto modified spent grain were studied. The equilibrium data were well fitted with Langmuir, Freundlich and Dubinin-Radushkevick (D-R) isotherm models. The kinetics of Pb(II) adsorption followed pseudo-second-order model, using the rate constants of pseudo-second-order model, the activation energy (E_a) of Pb(II) adsorption was determined as 12.33 kJ mol⁻¹ according to the Arrhenius equation. Various thermodynamic parameters such as ΔG^ads, ΔH^ads and ΔS^ads were also calculated. Thermodynamic results indicate that Pb(II) adsorption onto modified spent grain is a spontaneous and endothermic process. Therefore, it can be concluded that modified spent grain as a new effective adsorbent has potential for Pb(II) removal from aqueous solutions.     

Supramolecular assembly of single-walled carbon nanotubes at air-solid interface

The motive of the at hand exploration was to contrive a proficient innovative pH-responsive nanocarrier designed for an anti-neoplastic agent that not only owns competent loading capacity but also talented to liberate the drug at the specific site. pH sensitive hollow mesoporous silica nanoparticles (~MSN) have been synthesized by sequence of chemical reconstruction with an average particle size of 120 nm. ~MSN reveal noteworthy biocompatibility and efficient drug loading magnitude. Active molecules such as Doxorubicin (DOX) can be stocked and set free from the pore vacuities of ~MSN by tuning the pH of the medium. The loading extent of ~MSN was found up to 81.4 wt% at pH 7.8. At mild acidic pH, DOX is steadily released from the pores of ~MSN. Both, the nitrogen adsorption–desorption isotherms and X-ray diffraction patterns reflects that this system holds remarkable stable mesostructure. Additionally, the outcomes of cytotoxicity assessment further establish the potential of ~MSN as a relevant drug transporter which can be thought over an appealing choice to a polymeric delivery system.     

Co-delivery of doxorubicin and AS1411 aptamer by poly(ethylene glycol)-poly(<Emphasis Type="Italic">β</Emphasis>-amino esters) polymeric micelles for targeted cancer therapy

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.

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Graphical abstract Scheme 1 Schematic illustration of the preparation and cellular uptake of targeted co-delivery system

     

Interfacial kinetic enhancement of metal ion adsorption on binary mixed self-assembled monolayers

The adsorption of metal ions, a type of surface reaction on binary mixed self-assembled monolayers (SAMs) on a gold surface composed of 1,6-hexanedithiol (HDT) with 11-mercaptoundecanoic acid (MUA), was monitored by in situ surface plasmon resonance (SPR) measurements. The differential SPR reflectance (ΔR) enables the kinetics of adsorption of Pt²⁺ on the mixed SAMs to be investigated. Unlike single HDT SAM, kinetic analyses of the mixed SAMs showed that the rate of adsorption of Pt²⁺ was enhanced and that it was highly dependent on the fraction of MUA present. These SPR measurements suggest that the adsorption rate of metal ions can be readily manipulated simply by using mixed SAMs.     

Self‐Assembly of Drug–Drug Conjugates as Drug Self‐Delivery System for Tumor‐Specific pH‐Triggered Release

An acid‐labile doxorubicin dimer (D‐DOX) is designed as drug–drug conjugate for tumor intracellular pH‐triggered release, by conjugating doxorubicin (DOX) with adipic acid dihydrazide (ADH). The dimer‐based surfactants modified with polyethylene glycol (PEG), DOX‐ADH‐DOX‐PEG or are synthesized by mono‐PEGylation and bi‐PEGylation, respectively. Then the prodrug nanoparticles are fabricated with different drug contents via dialyzing the mixture solution of D‐DOX and the PEGylated surfactants in dimethyl sulfoxide (DMSO) with different mass ratios against water. It is found that the smaller prodrug nanoparticles (142–163 nm) could be obtained with the mono‐PEGylated surfactant, than those of 157–225 nm with the bi‐PEGylated surfactant. Furthermore, the mono‐PEGylated surfactant results in a higher drug content of 51% due to their lower PEG contents. All prodrug nanoparticles could release DOX completely within 36 h at pH 5.0, with the premature drug leakage of less than 10% at pH 7.4. The 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assays demonstrate the proposed drug self‐delivery system possessed an enhanced anticancer efficacy against HepG2 cells than the free DOX.     

Adsorbate-substrate bonding and the growth of naphthalene thin films on Ag(1 1 1)

The adsorption kinetics, energetics and growth of naphthalene thin films, from submonolayer to about 10 layers, on a Ag(1 1 1) surface at low temperature in a ultrahigh vacuum chamber are examined by using temperature programmed desorption spectroscopy. The first layer adsorption occurs with a desorption energy of 85 ± 5 kJ/mole and results in an interface dipole of 5 ± 1 D, from charge transfer of approximately 0.2 e from naphthalene to Ag. The surface dipole induced inter-adsorbate repulsion causes the lowering of the adsorption energy within the first layer near the saturation coverage so that the second layer deposition begins before the completion of the first layer. The second layer is a metastable phase with desorption energy, 74 ± 3 kJ/mole, smaller than the multilayer desorption energy of 79 ± 5 kJ/mole. Fractional order desorption kinetics were found for both the metastable and the multilayer phases, suggesting desorption from 2-D islanding and 3-D islanding, respectively.     

Glutathione‐Mediated Degradation of Surface‐Capped MnO2 for Drug Release from Mesoporous Silica Nanoparticles to Cancer Cells

Owing to its higher concentration in cancer cells than that in the corresponding normal cells, glutathione (GSH) provides an effective and flexible mechanism to design drug delivery systems. Here a novel GSH‐responsive mesoporous silica nanoparticle (MSN) is reported for controlled drug release. In this system, manganese dioxide (MnO₂) nanostructure, formed by the reduction of KMnO₄ on the surface of carboxyl‐functionalized MSN can block the pores (MSN@MnO₂). By a redox reaction, the capped MnO₂ nanostructure can dissociate into Mn²⁺ in the presence of GSH molecules. The blocked pores are then uncapped, which result in the release of the entrapped drugs. As a proof‐of‐concept, doxorubicin (DOX) as model drug is loaded into MSN@MnO₂. DOX‐loaded MSN@MnO₂ shows an obvious drug release in 10 × 10^?3 m GSH, while no release is observed in the absence of GSH. In vitro studies using human hepatocellular liver carcinoma cell line (HepG2) prove that the DOX‐loaded MSN@MnO₂ can entry into HepG2 cells and efficiently release the loaded DOX, leading to higher cytotoxicity than to that of human normal liver cells (L02). It is believed that further developments of this GSH‐responsive drug delivery system will lead to a new generation of nanodevices for intracellular controlled delivery.     

A Functionalized Hollow Mesoporous Silica Nanoparticles‐Based Controlled Dual‐Drug Delivery System for Improved Tumor Cell Cytotoxicity

Multifunctional nanoparticles for selectively targeting tumor cells and effectively delivering multiple drugs are urgently needed in cancer therapy. Here, a dual‐drug delivery system is prepared, based on functionalized hollow mesoporous silica nanoparticles (HMSNs). Doxorubicin (DOX) hydrochloride is loaded into the hollow core, and dichloro(1,2‐diaminocyclohexane)platinum (II) (DACHPt) is stored in the pores of the shell by the coordination interaction with the carboxyl groups modified on the pore walls, which also serves as barriers to control the DOX release. Detailed studies in vitro indicate that the DACHPt release is triggered by Cl^? through the cleavage of the coordination interaction, and the DOX release depends on the release rate of DACHPt and the environmental pH value. The surface of the mechanized nanoparticles is also modified by transferrin (Tf) to achieve the tumor specificity. Compared with individual drug delivery systems, the dual‐drug delivery system shows synergistic efficacy on the cell cytotoxicity (combination index = 0.30), resulting in improved tumor cell killing. The present dual‐drug delivery system provides a promising strategy to develop controlled and targeted combination therapies for efficient cancer treatment.     

In Vitro Evaluation of Non‐Protein Adsorbing Breast Cancer Theranostics Based on 19F‐Polymer Containing Nanoparticles

Eight fluorinated nanoparticles (NPs) are synthesized, loaded with doxorubicin (DOX), and evaluated as theranostic delivery platforms to breast cancer cells. The multifunctional NPs are formed by self‐assembly of either linear or star‐shaped amphiphilic block copolymers, with fluorinated segments incorporated in the hydrophilic corona of the carrier. The sizes of the NPs confirm that small circular NPs are formed. The release kinetics data of the particles reveals clear hydrophobic core dependence, with longer sustained release from particles with larger hydrophobic cores, suggesting that the DOX release from these carriers can be tailored. Viability assays and flow cytometry evaluation of the ratios of apoptosis/necrosis indicate that the materials are non‐toxic to breast cancer cells before DOX loading; however, they are very efficient, similar to free DOX, at killing cancer cells after drug encapsulation. Both flow cytometry and confocal microscopy confirm the cellular uptake of NPs and DOX‐NPs into breast cancer cells, and in vitro ¹⁹F‐MRI measurement shows that the fluorinated NPs have strong imaging signals, qualifying them as a potential in vivo contrast agent for ¹⁹F‐MRI.     

Nanodiamond Particles: Properties and Perspectives for Bioapplications

Nanodiamonds (NDs) are members of the diverse structural family of nanocarbons that includes many varieties based on synthesis conditions, post-synthesis processes, and modifications. First studied in detail beginning in the 1960s in Russia, NDs have now gained world-wide attention due to their inexpensive large-scale synthesis based on the detonation of carbon-containing explosives, small primary particle size (～ 4 to 5 nm) with narrow size distribution, facile surface functionalization including bio-conjugation, as well as high biocompatibility. It is anticipated that the attractive properties of NDs will be exploited for the development of therapeutic agents for diagnostic probes, delivery vehicles, gene therapy, anti-viral and anti-bacterial treatments, tissue scaffolds, and novel medical devices such as nanorobots. Additionally, biotechnology applications have shown the prospective use of NDs for bioanalytical purposes, such as protein purification or fluorescent biolabeling. This review critically examines the use of NDs for biomedical applications based on type (i.e., high-pressure high-temperature [HPHT], CVD diamond, detonation ND [DND]), post-synthesis processing and modifications, and resultant properties including bio-interfacing. The discussion focuses on nanodiamond material in the form of nanoparticles, while the biomedical uses of nanodiamond coatings and thin films are discussed rather briefly. Specific use of NDs in both non-conjugated and conjugated forms as enterosorbents or solid phase carriers for small molecules including lysozyme, vaccines, and drugs is also considered. The use of NDs as human anti-cancer agents and in health care products is already showing promising results for further development. The review concludes with a look to the future directions and challenges involved in maximizing the potential of these exciting little carbon-based gems in the fields of engineering, medicine, and biotechnology.