Renbing Tian

Synthesis and characterization of mesoporous magnetic nanocomposites wrapped with chitosan gatekeepers for pH-sensitive controlled release of doxorubicin.

Multifunctional nanocarriers based on the Fe3O4 nanoparticles core and mesoporous silica shell (mSiO2) were synthesized for controlled drug release through magnetic targeting and pH-sensitive performances. The developed Fe3O4@mSiO2 nanocarriers exhibited a suitable size (63nm) and good magnetic responsibility, doxorubicin (DOX) could be successfully loaded into the mesoporous of Fe3O4@mSiO2 via electrostatic interaction, and the drug loading content and loading efficiency are 29.3% and 93.6%, respectively. The chitosan (CS) was employed to wrap the Fe3O4@mSiO2-DOX as the blocking agent to inhibit premature drug release, and the final CS/Fe3O4@mSiO2-DOX exhibited excellent pH-sensitivity, 86.1% DOX was released within 48h at pH4.0. Furthermore, all the release behaviors fit the Higuchi model very well and a purely diffusion-controlled process played a major role on DOX release from CS/Fe3O4@mSiO2-DOX. In addition, MTT assays in human liver hepatocellular carcinoma cells (HepG2) demonstrated that the CS/Fe3O4@mSiO2-DOX had high anti-tumor activity, while the Fe3O4@mSiO2 nanocarriers were practically non-toxic. Thus, our results revealed that the CS/Fe3O4@mSiO2-DOX could play an important role in the development of intracellular delivery nanodevices for cancer therapy.

Synthesis and in vitro evaluation of pH-sensitive magnetic nanocomposites as methotrexate delivery system for targeted cancer therapy.

This study focuses on the synthesis and in vitro evaluation of magnetic nanocomposites (Fe3O4@LDH) as methotrexate (MTX) delivery system for targeted anticancer therapy. In which, the Fe3O4 nanoparticles acted as magnetically responsive carriers; the coating layer of layered double hydroxide (LDH) was used as a storehouse for MTX. The prepared Fe3O4@LDH nanocomposites exhibited a suitable size, good stability and magnetic responsibility (Ms 36.66emu/g); MTX successfully intercalated into the LDH of Fe3O4@LDH at an entrapment rate (%) of 91.78% (the drug loading was 18.36%) by host-guest exchange process. Moreover, the release studies in vitro showed that the drug delivery system (Fe3O4@LDH-MTX) had excellent pH-sensitivity, 84.94% of MTX was released within 48h at pH3.5 via the co-effect of dissolution of LDH layer and ion-exchange. WST-1 assays in cancer cells (MCF-7 and HepG2) and normal cells (HUVEC) demonstrated that Fe3O4@LDH-MTX exhibited high anticancer activity while low toxicity to normal cells, and also the Fe3O4@LDH composites were practically non-toxic. Thus, our results revealed that Fe3O4@LDH-MTX would be a competitive candidate for targeted delivery and sustained and controlled release of MTX.

Synthesis and Characterization of Doxorubicin Loaded pH-Sensitive Magnetic Core-Shell Nanocomposites for Targeted Drug Delivery Applications

In order to improve the effects of medical therapy for cancer, we prepared magnetic nanocomposites (Fe3O4@SiO2–NH–NH2) as doxorubicin (DOX) carriers via two different schemes. Scheme (I): the carriers were synthesized from magnetic silica nanoparticles (Fe3O4@SiO2) via layer by layer modification, scheme (II): the carriers were obtained from amino-modified magnetic silica nanoparticles (Fe3O4@SiO2–NH2) synthesized by one-step, and followed by surface modification. In order to load DOX effectively, the surface of the carriers were further modified to make the surface with a large number of hydrazine bonds which can form a pH-sensitive bond (hydrazone bond) with DOX. The two kinds of carriers both exhibited a size around 80nm, high stability and superparamagnetic behavior. However, DOX-loaded carriers (Fe3O4@SiO2–DOX(2)) performed relatively poorer performance in terms of drug loading and releasing (the loading efficiency of DOX decreased from 67.33% to 42.15%, while the releasing efficiency of DOX decreased from 66.16% to 62.23% within 72h at pH 4.0). Water-soluble tetrazolium salts (WST-1) assays in cancer cells (Hela) demonstrated that the Fe3O4@SiO2–DOX presented high anti-tumor activity, while the carriers were nearly nontoxic. Thus, the results suggested that the magnetic nanocomposites synthesized by the two different methods both can be employed to deliver DOX, while the carriers obtained via the first method may perform better and would be applied in the field of cancer therapy in the future.

Facile preparation and the stepwise formation mechanistic investigation of gram-scale nitrogen-doped graphene quantum dots

Although nitrogen-doped graphene quantum dots (N-doped GQDs) have been widely studied for their unique properties and promising applications, large scale synthesis of N-doped GQDs has been rarely reported. Besides, the formation mechanism was always explained simply. Herein we report a facile one-step gram-scale approach to prepare N-doped GQDs by polymerization of nitrilotriacetic acid (NTA) under high temperature and pressure in a nitrogen environment. A mechanism, which is rooted in the chemical properties of NTA and consists of dehydration and nucleophilic addition, has been proposed to explain the formation of N-doped GQDs step by step. Utilizing this method, the change in the structure, functional groups and FL properties can be explained intuitively and clearly. Because of the significant difference in ethanol solubility between the raw material and product, N-doped GQD powder with a purity higher than 99% can be easily obtained by a dissolution–centrifugation–drying–dissolution–freeze drying process without a tedious dialysis process. 1.38 grams of N-doped GQDs could be prepared from 3 grams of NTA. The 46% synthetic yield is higher than that obtained using a large majority of methods reported so far. With the introduction of an N atom, the N-doped GQDs showed bright blue fluorescence (FL) under 365 nm ultraviolet (UV) light, exhibiting a quite high quantum yield of 45.8%. A short preparation time, the low cost of the raw materials, a simple preparation process, high synthetic yield, high quantum yield and a facile purification method make this approach promising in the industrial production of N-doped GQDs. Besides, the N-doped GQDs were used as handwriting FL ink in the form of aqueous and oil-like ink, and used in a fountain pen and ball pen respectively. The words written with FL ink showed strong contrast under daylight and UV light, and no obvious change can be observed after long-term high temperature treatment, indicating that the N-doped GQDs have obvious practicability and good stability as an FL ink.

Synthesis and characterization of pH-sensitive magnetic nanoparticles as drug carriers for sustained and controlled release of MTX

Nowadays, effective cancer treatment is still one of the most challenging missions in the scientific community. A primary limitation to most conventional anticancer drugs is their adverse uptake by normal tissues, fast metabolism and lack of tumour cell targeting property. One way to overcome these disadvantages is the application of nanoparticles as the carriers of widely known therapeutic substances. In this work, we devoted our efforts to prepare pH-sensitive magnetic nanoparticles as drug carriers for sustained and controlled release of methotrexate (MTX) via self-assembly of MgAl-LDH and Fe3O4 nanoparticles, which is an economic and environmentally friendly process, and also investigated the physical and chemical properties as well as the drug release performance. We further found that the carriers had a suitable size, good stability and magnetic responsibility; the MTX successfully loaded onto the carriers at a drug loading efficiency of 89.16%. In addition, the in vitro drug release studies showed that the MTX-carriers had excellent pH-sensitivity, 86.21% of MTX was released within 48 h at pH 3.5. Moreover, the MTT assays in cancer cells (HepG2) demonstrated that MTX-carriers exhibited high anticancer activity while the carriers were practically non-toxic.

Facile synthesis of magnetic-/pH-responsive hydrogel beads based on Fe3O4 nanoparticles and chitosan hydrogel as MTX carriers for controlled drug release

Abstract In the present study, methotrexate (MTX)-encapsulated magnetic-/pH-responsive hydrogel beads based on Fe3O4 nanoparticles and chitosan were successfully prepared through a one-step gelation process, which is a very facile, economic and environmentally friendly route. The developed hydrogel beads exhibited homogeneous porous structure and super-paramagnetic responsibility. MTX can be successfully encapsulated into magnetic chitosan hydrogel beads, and the drug encapsulation efficiency (%) and encapsulation content (%) were 93.8 and 6.28%, respectively. In addition, the drug release studies in vitro indicated that the MTX-encapsulated magnetic chitosan hydrogel beads had excellent pH-sensitivity, 90.6% MTX was released from the magnetic chitosan hydrogel beads within 48 h at pH 4.0. WST-1 assays in human liver hepatocellular carcinoma cells (HepG2) demonstrated that the MTX-encapsulated magnetic chitosan hydrogel beads had good cytocompatibility and high anti-tumor activity. Therefore, our results revealed that the MTX-encapsulated magnetic chitosan hydrogel beads would be a competitive candidate for controlled drug release in the area of targeted cancer therapy in the near future.

Facile one-pot synthesis of magnetic nanoparticles with controllable morphology and size distribution as targeted biocarriers

Magnetic iron oxide (Fe3O4) nanoparticles with appropriate surface chemistry and size distribution have been widely used as biocarriers for biomedical and bioengineering applications such as tissue repair, immunoassay, hyperthermia, drug delivery and in cell separation, etc. Fe3O4 nanoparticles with controllable morphology and size distribution were synthesized by one-pot hydrothermal decomposition of FeCl3 * 6H2O in PEG containing polyethyleneimine (PEI) or Polyacrylic acid (PAA) in the present work. The final particles had a variety of morphologies such as petaloid and spherical, and the size could be tuned by varying the content of PEI or PAA. The prepared nanoparticles which were jointly coated with PEG/PEI or PEG/PAA showed excellent magnetic properties. With size from 50 nm to 170 nm and positive or neutral zeta potentials these Fe3O4 nanoparticles exhibited higher dispersion stability in deionized water and in phosphate buffered saline. Moreover, the WST-1 assays revealed that the PEG/PEI or PEG/PAA coated Fe3O4 nanoparticles were practically non-toxic. This work demonstrates that Fe3O4 nanoparticles with modulated properties can be prepared simply by using the one-pot hydrothermal polyol method. The PEG/PEI or PEG/PAA coated Fe3O4 can also be used as promising magnetic targeted biocarriers for biomedical applications.