Green synthesis of Zn nanoparticles and in situ hybridized with BSA nanoparticles for Baicalein targeted delivery mediated with glutamate receptors to U87-MG cancer cell lines

Glioblastoma multiforme (GBM) is the most aggressive malignant tumor of the brain. It has different glutamate receptor types. So, these receptors can be a suitable target for GBM treatment. The current study investigated the anticancer effects of bovine serum albumin (BSA)-Baicalein @Zn-Glu nanostructure mediated-GluRs in human glioblastoma U87 cells. BSA-Ba@Zn-Glu hybrid nanoparticles (NPs) were set and considered transporters for Baicalein (Ba) active compound delivery. BSA-Ba@Zn-Glu NPs were synthesized by a single-step reduction process. The successful production was confirmed through transmission electron microscopy (TEM), dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FT-IR), and hemolysis test. The cytotoxic efficacy and apoptosis rate of the nanostructures on U87 glioblastoma cells were investigated by 3-(4,5-dimethylthialzol-a-yl)-2,5 diphenyltetrazolium bromide (MTT) and flow cytometry assays, respectively. The synthesized BSA-Ba@Zn-Glu nanostructures with a diameter of 142.40 ± 1.91 to 177.10 ± 1.87 nm and zeta potential of −10.57 ± 0.71 to −35.77 ± 0.60 mV are suitable for extravasation into tumor cells. The drug release from the BSA-Ba@Zn NPs showed controlled and pH-dependent behavior. In vitro results indicated that the BSA-Ba@Zn-Glu NPs significantly reduce cell viability and promote apoptosis of U87 cancer cells. It revealed the cytotoxic effect of the Baicalein and an increase in cellular uptake of nanoparticles by Glu receptors. Zn NPs were synthesized based on a green synthesis method. BSA NPs were used as a nano-platform for Glu conjugation and Ba drug delivery. BSA-Ba@Zn-Glu NPs induce cytotoxicity and apoptosis in human brain cancer cells (U87) in a dose-dependent manner. Finally, this nanostructure could be served in targeted drug delivery in vivo studies and applied along with other strategies such as X-ray irradiation as combinational therapies in future studies.     

Composite block copolymer stabilized nanoparticles: simultaneous encapsulation of organic actives and inorganic nanostructures

We describe the preparation and characterization of hybrid block copolymer nanoparticles (NPs) for use as multimodal carriers for drugs and imaging agents. Stable, water-soluble, biocompatible poly(ethylene glycol)-block-poly(epsilon-caprolactone) NPs simultaneously co-encapsulating hydrophobic organic actives (beta-carotene) and inorganic imaging nanostructures (Au) are prepared using the flash nanoprecipitation process in a multi-inlet vortex mixer. These composite nanoparticles (CNPs) are produced with tunable sizes between 75 nm and 275 nm, narrow particle size distributions, high encapsulation efficiencies, specified component compositions, and long-term stability. The process is tunable and flexible because it relies on the control of mixing and aggregation timescales. It is anticipated that the technique can be applied to a variety of hydrophobic active compounds, fluorescent dyes, and inorganic nanostructures, yielding CNPs for combined therapy and multimodal imaging applications.     

Temperature-assisted ionic liquid dispersive liquid-liquid microextraction combined with high performance liquid chromatography for the determination of PCBs and PBDEs in water and urine samples

We report on silver–gold core-shell nanostructures that contain Methylene Blue (MB) at the gold–silver interface. They can be used as reporter molecules in surface-enhanced Raman scattering (SERS) labels. The labels are stable and have strong SERS activity. TEM imaging revealed that these nanoparticles display bright and dark stripe structures. In addition, these labels can act as probes that can be detected and imaged through the specific Raman signatures of the reporters. We show that such SERS probes can identify cellular structures due to enhanced Raman spectra of intrinsic cellular molecules measured in the local optical fields of the core-shell nanostructures. They also provide structural information on the cellular environment as demonstrated for these nanoparticles as new SERS-active and biocompatible substrates for imaging of live cells.

Recent advances in surface engineering of superparamagnetic iron oxide nanoparticles for biomedical applications

Superparamagnetic iron oxide nanoparticles (SPIONs) are promising materials for various biomedical applications including targeted drug delivery and imaging, hyperthermia, magneto-transfections, gene therapy, stem cell tracking, molecular/cellular tracking, magnetic separation technologies (e.g. rapid DNA sequencing), and detection of liver and lymph node metastases. The most recent applications for SPIONs for early detection of inflammatory, cancer, diabetes and atherosclerosis have also increased their popularity in academia. In order to increase the efficacy of SPIONs in the desired applications, especial surface coating/characteristics are required. The aim of this article is to review the surface properties of magnetic nanoparticles upon synthesis and the surface engineering by different coatings. The biological aspects, cytotoxicity, and health risks are addressed. Special emphasis is given to organic and inorganic-based coatings due to their determinant role in biocompatibility or toxicity of the final particles.     

Albumin-Albumin/Lactosylated Core-Shell Nanoparticles: Therapy to Treat Hepatocellular Carcinoma for Controlled Delivery of Doxorubicin

Doxorubicin (Dox) is the most widely used chemotherapeutic agent and is considered a highly powerful and broad-spectrum for cancer treatment. However, its application is compromised by the cumulative side effect of dose-dependent cardiotoxicity. Because of this, targeted drug delivery systems (DDS) are currently being explored in an attempt to reduce Dox systemic side-effects. In this study, DDS targeting hepatocellular carcinoma (HCC) has been designed, specifically to the asialoglycoprotein receptor (ASGPR). Dox-loaded albumin-albumin/lactosylated (core-shell) nanoparticles (tBSA/BSALac NPs) with low (LC) and high (HC) crosslink using glutaraldehyde were synthesized. Nanoparticles presented spherical shapes with a size distribution of 257 ± 14 nm and 254 ± 14 nm, as well as an estimated surface charge of −28.0 ± 0.1 mV and −26.0 ± 0.2 mV, respectively. The encapsulation efficiency of Dox for the two types of nanoparticles was higher than 80%. The in vitro drug release results showed a sustained and controlled release profile. Additionally, the nanoparticles were revealed to be biocompatible with red blood cells (RBCs) and human liver cancer cells (HepG2 cells). In cytotoxicity assays, Dox-loaded nanoparticles decrease cell viability more efficiently than free Dox. Specific biorecognition assays confirmed the interaction between nanoparticles and HepG2 cells, especially with ASGPRs. Both types of nanoparticles may be possible DDS specifically targeting HCC, thus reducing side effects, mainly cardiotoxicity. Therefore, improving the quality of life from patients during chemotherapy.     

Interaction of bare and gold-coated superparamagnetic iron oxide nanoparticles with fetal bovine serum

Superparamagnetic iron oxide nanoparticles (SPIONs) are being increasingly used in various biomedical processes such as hyperthermia, cell and protein separation, enhancing resolution of magnetic resonance imaging and drug delivery. Here, SPIONs were prepared by optimized co-precipitation of iron chlorides in basic medium and then coated with gold. Bare SPIONs and Aucoated SPIONs were characterized by TEM before incubation with fetal bovine serum for 0.5, 1, 2, 4, 8 and 24 h. After these interaction times, the mixture was deposed on a small column in a strong magnetic field (MACS?system). The SPIONs were retained; different washing fractions were collected and studied by UV-Vis spectroscopy and by 1D gel electrophoresis. The study revealed the presence of proteins in the washing solutions and confirmed the strong interaction of the protein with the SPIONs.     

Radio-immunoconjugated,Dox-loaded,surface-modified superparamagnetic iron oxide nanoparticles (SPIONs) as a bioprobe for breast cancer tumor theranostics

In this research, we develop dual modality molecular imaging and also radio-immunotherapy (RIT) bioprobes, in the form of modified superparamagnetic iron oxide nanoparticles (SPIONs) conjugated to radiolabeled antibodies, for PET and MRI of HER2 expressing cancers as well as a PH sensitive drug carrier by embedded an anticancer agent for cancer therapeutic applications. The bioprobes were developed by conjugating ⁶⁴Cu labeled trastuzumab (herceptin) and rituximab (Anti CD-20) antibodies to modified SPIONs. The SPIONs were modified with carboxymethyl chitosan and functionalized with acrylic acid (AA). Also, with the purpose of identifying more effective bifunctional chelator (BFC), we compared the properties of novel BFC, p-NO₂-Bn-PCTA with the commonly used DOTA-NHS for radio-immunoconjugate preparations. Moreover, a chemotherapy drug, doxorubicin, was then loaded onto engineered nanoparticles for targeted intracellular drug delivery and selective cancer cell killing. Resulting radio-immunoconjugated-SPIONs were evaluated for molecular imaging and effective targeting of the HER2+ receptors in SKBR3 cell lines and breast tumor bearing Balb/C mice. Therefore, our biocompatible SPIONs could serve as a promising multifunctional theranostics nanoplatform in dual modality imaging guided RIT of HER2 overexpressing cancer applicable to drug delivery and controlled drug release for trigger both intrinsic and extrinsic pathways of apoptosis.     

Au@ZIF-8核壳结构中金纳米粒子分布的调控及其在荧光分子光致发光传感中的应用

控制金属@MOF核壳纳米结构中金属纳米粒子的分布不容易实现。我们应用了合成MOF胶体粒子所用到的配位调制方法来合成Au@ZIF-8核壳纳米结构。通过使用过量的2-甲基咪唑和不同用量的1-甲基咪唑可获得不同的Au@ZIF-8。该合成方法可在ZIF-8纳米晶体中灵活调整Au纳米粒子（Au NPs）的分布。此外,我们分别研究了2种不同尺寸的荧光分子与Au@ZIF-8结合后的光致发光光谱和寿命。ZIF-8的孔径可以决定这2种分子是否可通过多孔壳结构接近Au NPs。分子光学特性对Au NPs近场的发光增强和荧光猝灭的竞争非常敏感。     

General Route to Multifunctional Uniform Yolk/Mesoporous Silica Shell Nanocapsules: A Platform for Simultaneous Cancer‐Targeted Imaging and Magnetically Guided Drug Delivery

Hollow mesoporous SiO₂ (mSiO₂) nanostructures with movable nanoparticles (NPs) as cores, so‐called yolk‐shell nanocapsules (NCs), have attracted great research interest. However, a highly efficient, simple and general way to produce yolk‐mSiO₂ shell NCs with tunable functional cores and shell compositions is still a great challenge. A facile, general and reproducible strategy has been developed for fabricating discrete, monodisperse and highly uniform yolk‐shell NCs under mild conditions, composed of mSiO₂ shells and diverse functional NP cores with different compositions and shapes. These NPs can be Fe₃O₄ NPs, gold nanorods (GNRs), and rare‐earth upconversion NRs, endowing the yolk‐mSiO₂ shell NCs with magnetic, plasmonic, and upconversion fluorescent properties. In addition, multifunctional yolk‐shell NCs with tunable interior hollow spaces and mSiO₂ shell thickness can be precisely controlled. More importantly, fluorescent‐magnetic‐biotargeting multifunctional polyethyleneimine (PEI)‐modified fluorescent Fe₃O₄@mSiO₂ yolk‐shell nanobioprobes as an example for simultaneous targeted fluorescence imaging and magnetically guided drug delivery to liver cancer cells is also demonstrated. This synthetic approach can be easily extended to the fabrication of multifunctional yolk@mSiO₂ shell nanostructures that encapsulate various functional movable NP cores, which construct a potential platform for the simultaneous targeted delivery of drug/gene/DNA/siRNA and bio‐imaging.     

PEGylated BODIPY assembling fluorescent nanoparticles for photodynamic therapy

Two PEGylated BODIPY which could self-assemble into nanoparticles were synthesized via multicomponent Passerini reaction for cellular imaging and photodynamic therapy.     

Facile preparation of zwitterion-stabilized superparamagnetic iron oxide nanoparticles (ZSPIONs) as an MR contrast agent for in vivo applications

We describe a simple method for synthesizing superparamagnetic nanoparticles (SPIONs) as small, stable contrast agents for magnetic resonance imaging (MRI) based on sulfobetaine zwitterionic ligands. SPIONs synthesized by thermal decomposition were coated with zwitterions to impart water dispersibility and high in vivo stability through the nanoemulsion method. Zwitterion surfactant coating layers are formed easily on oleic acid-stabilized SPIONs via hydrophobic and van der Waals interactions. Our zwitterion-coated SPIONs (ZSPIONs) had ultrathin (～5 nm) coating layers with mean sizes of 12.0 ± 2.5 nm, as measured by dynamic light scattering (DLS). Upon incubation in 1 M NaCl and 10% FBS, the ZSPIONs showed high colloidal stabilities without precipitating, as monitored by DLS. The T2 relaxivity coefficient of the ZSPIONs, obtained by measuring the relaxation rate on the basis of the iron concentration, was 261 mM(-1) s(-1). This value was much higher than that of the commercial T2 contrast agent because of the ultrathin coating layer. Furthermore, we confirmed that ZSPIONs can be used as MR contrast agents for in vivo applications such as tumor imaging and lymph node mapping.     

Efficient exosome extraction through the conjugation of superparamagnetic iron oxide nanoparticles for the targeted delivery in rat brain

Exosomes possess endogenous attributes and distinct biological functions, and thereby, their uses as drug nanocarriers have attracted increasing attention for biomedical practices. However, to achieve targeted therapeutic purposes, complicated extractions, as well as modifications of exosomes, are involved. Here, based on the use of superparamagnetic iron oxide nanoparticles conjugated exosome (Ex-SPIONs), a facile exosome extraction through magnetism was established. The produced Ex-SPIONs exhibited a uniform size distribution and desirable biocompatibility. Moreover, taking advantage of the magnetic properties of SPIONs, the targeted delivery of Ex-SPIONs was demonstrated in the rat brain. Therefore, the constructed SPIONs functionalized exosome shows promising therapeutic potentials, including the treatment of brain diseases.     

Nanoparticles: Properties,applications and toxicities

This review is provided a detailed overview of the synthesis, properties and applications of nanoparticles (NPs) exist in different forms. NPs are tiny materials having size ranges from 1 to 100 nm. They can be classified into different classes based on their properties, shapes or sizes. The different groups include fullerenes, metal NPs, ceramic NPs, and polymeric NPs. NPs possess unique physical and chemical properties due to their high surface area and nanoscale size. Their optical properties are reported to be dependent on the size, which imparts different colors due to absorption in the visible region. Their reactivity, toughness and other properties are also dependent on their unique size, shape and structure. Due to these characteristics, they are suitable candidates for various commercial and domestic applications, which include catalysis, imaging, medical applications, energy-based research, and environmental applications. Heavy metal NPs of lead, mercury and tin are reported to be so rigid and stable that their degradation is not easily achievable, which can lead to many environmental toxicities.     

Nanoparticle-containing structures as a substrate for surface-enhanced Raman scattering

Metallic nanostructures were prepared through the alternate immersion of derivatized glass slides in solutions of gold nanoparticles (NPs) and a propanedithiol linker molecule. Nanostructures consisting of 1-17 depositions of gold NPs were synthesized, and these substrates were characterized using UV-vis spectroscopy and atomic force microscopy. Subsequently, the surface-enhanced Raman scattering (SERS) of oxazine 720 was obtained at two excitation wavelengths (632 and 785 nm) from all substrates. Maximum SERS enhancement was observed for 9 and 13 NP depositions for 632 and 785 nm excitations, respectively. The difference in the number of NP depositions required for maximum enhancement is attributed to different wavelengths which can excite distinct aggregate structures within the metallic substrate. Therefore, these NP-containing structures can be "tuned" to yield maximum SERS enhancement for the excitation source being used by varying the number of NP depositions.     

Raman active jagged-shaped gold-coated magnetic particles as a novel multimodal nanoprobe

The creation of novel engineered multimodal nanoparticles (NPs) is a key focus in bionanotechnology and can lead to deep understanding of biological processes at the molecular level. Here, we present a multi-component system made of gold-coupled core-shell SPIONs, as a new nanoprobe with signal enhancement in surface Raman spectroscopy, due to its jagged-shaped gold shell coating.     

ICG@ZIF-8: One-step encapsulation of indocyanine green in ZIF-8 and use as a therapeutic nanoplatform

This work reported a one-step encapsulation of indocyanine green (ICG) in ZIF-8 nanoparticles (NPs), which possess an absorption band in the near infrared region and have the good photothermal conversion efficiency. The in vivo and in vitro studies show that, after loading DOX, ICG@ZIF-8-DOX NPs exhibit the chem-band photothermal synergistic therapy for tumor.     

Amine‐Functionalized Polyglycidyl Methacrylate Microsphere as a Unified Template for the Synthesis of Gold Nanoparticles and Single‐Crystal Gold Plates

Polyglycidyl methacrylate (PGMA) microspheres, crosslinked and surface‐functionalized by amine, can be used as a solid‐state template for the synthesis of gold (Au) crystals in the forms of either nanoparticles (NPs) or plates. It is discovered that the polymer microsphere acts as an internal template to cultivate Au NPs inside the microsphere or an external template to generate the single‐crystal plates depending on the critical concentration (C_cr) of gold ions. The ion–dipole interaction and the structure‐dependent solubility of gold induce two distinct gold nanostructures in the presence of the functionalized polymer microspheres. The catalytic activity and long‐term storage of the developed gold nanostructures that can be easily scaled‐up for mass production through the developed novel methodology is demonstrated.     

基于超顺磁性Fe3O4的磁响应型纳米药物载体的研究进展

基于超顺磁性Fe3O4纳米粒子（SPIONs）磁响应型纳米药物载体已经广泛应用于肿瘤诊断与治疗方面。将SPIONs用多功能性外壳修饰后,能够使其稳定性增加,实现体内长循环,并能缓释出所携带药物;再将其靶向性配体分子复合后,能够提高其肿瘤多靶向的效果;通过将SPIONs用温敏性或光敏性等外壳材料包覆,利用SPIONs的磁致发热、光致发热以及外壳材料自身的特点,能够直接杀死肿瘤细胞或者将温敏性外壳剥落,平稳地释放出药物,提高肿瘤部位的药物浓度,增强治疗效果。因此,本文综述了基于SPIO的磁响应型纳米药物载体在肿瘤治疗领域的新研究与新进展,并进行研究展望,以期为今后相关方面的深入研究提供参考和借鉴。     

Synthesis and bio-functionalization of magnetic nanoparticles for medical diagnosis and treatment

The synthesis of multifunctional magnetic nanoparticles (NPs) is a highly active area of current research located at the interface between materials science, biotechnology and medicine. By virtue of their unique physical properties magnetic nanoparticles are emerging as a new class of diagnostic probes for multimodal tracking and as contrast agents for MRI. Furthermore, they show great potential as carriers for targeted drug and gene delivery, since reactive agents, such as drug molecules or large biomolecules (including genes and antibodies), can easily be attached to their surface. On the other hand, the fate of the nanoparticles inside the body is mainly determined by the interactions with its local environment. These interactions strongly depend upon the size of the magnetic NPs but also on the individual surface characteristics, like charge, morphology and surface chemistry. This review not only summarizes the most common synthetic approaches for the generation of magnetic NPs, it also focuses on different surface modification strategies that are used today to enhance the biocompatibility of these NPs. Finally, key considerations for the application of magnetic NPs in biomedicine, as well as various examples for the utilization in multimodal imaging and targeted gene delivery are presented.     

Combined ATRP and 'click' chemistry for designing stable tumor-targeting superparamagnetic iron oxide nanoparticles

Important issues in the design of superparamagnetic iron oxide nanoparticles (SPIONs) for cancer diagnosis include stability under physiological conditions and specificity in targeting the cancer cells. In the present study, atom transfer radical polymerization (ATRP) was used to graft SPIONs with poly(glycidyl methacrylate-co-poly(ethylene glycol) methyl ether methacrylate) (SPIONs-P(GMA-co-PEGMA)). The PEGMA in the copolymer chain confers high stability to the nanoparticles in aqueous medium, and prevents recognition by macrophages with the aim of prolonging their in vivo circulation time. The GMA groups were used for conjugating the cancer targeting ligand, folic acid (FA), via 'click' chemistry. Using this method, the amount of FA conjugated to the nanoparticles (SPIONs-P(GMA-co-PEGMA)-FA) can be readily controlled. The specificity of cellular uptake of the nanoparticles by three different cell lines was investigated. The cellular iron uptake by KB cells (human epidermoid carcinoma) after 24 h of incubation is about thirteen and five times higher than those by 3T3 fibroblasts and macrophages, respectively. No significant cytotoxicity was observed with these three types of cells. The high targeting efficiency and biocompatibility of these nanoparticles are promising features for in vivo specific targeting and detection of tumor cells which overexpress the folate receptor.