Preparation of High-Toughness Lignin Phenolic Resin Biomaterials Based via Polybutylene Succinate Molecular Intercalation.

Lignin has many potential applications and is a biopolymer with a three-dimensional network structure. It is composed of three phenylpropane units, p-hydroxyphenyl, guaiacyl, and syringyl, connected by ether bonds and carbon-carbon bonds, and it contains a large number of phenol or aldehyde structural units, resulting in complex lignin structures. This limits the application of lignin. To expand the application range of lignin, we prepared lignin thermoplastic phenolic resins (LPRs) by using lignin instead of phenol; these LPRs had molecular weights of up to 1917 g/mol, a molecular weight distribution of 1.451, and an O/P value of up to 2.73. Due to the complex structure of the lignin, the synthetic lignin thermoplastic phenolic resins were not very tough, which greatly affected the performance of the material. If the lignin phenolic resins were toughened, their application range would be substantially expanded. Polybutylene succinate (PBS) has excellent processability and excellent mechanical properties. The toughening effects of different PBS contents in the LPRs were investigated. PBS was found to be compatible with the LPRs, and the flexible chain segments of the small PBS molecules were embedded in the molecular chain segments of the LPRs, thus reducing the crystallinities of the LPRs. The good compatibility between the two materials promoted hydrogen bond formation between the PBS and LPRs. Rheological data showed good interfacial bonding between the materials, and the modulus of the high-melting PBS made the LPRs more damage resistant. When PBS was added at 30%, the tensile strength of the LPRs was increased by 2.8 times to 1.65 MPa, and the elongation at break increased by 31 times to 93%. This work demonstrates the potential of lignin thermoplastic phenolic resins for industrial applications and provides novel concepts for toughening biobased aromatic resins with PBS.

7-Dehydrocholesterol Encapsulated Polymeric Nanoparticles As a Radiation-Responsive Sensitizer for Enhancing Radiation Therapy.

Therapeutics that can be activated by radiation in situ to enhance the efficacy of radiotherapy are highly desirable. Herein, 7-Dehydrocholesterol (7-DHC), a biosynthetic precursor of cholesterol, as a radiosensitizer, exploiting its ability to propagate the free radical chain reaction is explored. The studies show that 7-DHC can react with radiation-induced reactive oxygen species and in turn promote lipid peroxidation, double-strand breaks, and mitochondrial damage in cancer cells. For efficient delivery, 7-DHC is encapsulated into poly(lactic-co-glycolic acid) nanoparticles, forming 7-DHC@PLGA NPs. When tested in CT26 tumor bearing mice, 7-DHC@PLGA NPs significantly enhanced the efficacy of radiotherapy, causing complete tumor eradication in 30% of the treated animals. After treatment, 7-DHC is converted to cholesterol, causing no detectable side effects or hypercalcemia. 7-DHC@PLGA NPs represent a radiation-responsive sensitizer with great potential in clinical translation.

Combining Doxorubicin-Conjugated Polymeric Nanoparticles and 5-Aminolevulinic Acid for Enhancing Radiotherapy against Lung Cancer.

Radiation therapy (RT) concurrent with chemotherapy improves local lung cancer control but may cause systemic toxicity. There is an unmet clinical need of treatments that can selectively sensitize cancer cells to RT. Herein, we explored a radiosensitizing strategy that combines doxorubicin (DOX)-encapsulated polyaspartamide nanoparticles and 5-aminolevulinic acid (5-ALA). The DOX-polyaspartamide nanoparticles were coupled with NTSmut, a ligand specific to neurotensin receptor type 1 (NTSR1), for lung cancer targeting. DOX was coupled to the polymer backbone through a pH-sensitive hydrazone linker, which allows for controlled release of the drug in an acidic tumor micromovement. Meanwhile, 5-ALA accumulates in the cancer cell's mitochondria, forming protoporphyrin (PpIX) that amplifies RT-induced oxidative stress. When tested in vitro in H1299 cells, DOX-encapsulated nanoparticles in conjugation with 5-ALA enhanced cancer cell killing owing to the complementary radiosensitizing effects of DOX and 5-ALA. In vivo studies confirmed that the combination improved tumor suppression relative to RT alone without causing toxicity to normal tissues. Overall, our study suggests an effective and selective radiosensitizing approach.

Refining of Particulates at Stimuli-Responsive Interfaces: Label-Free Sorting and Isolation.

The mechanism of separation methods, for example, liquid chromatography, is realized through rapid multiple adsorption-desorption steps leading to the dynamic equilibrium state in a mixture of molecules with different partition coefficients. Sorting of colloidal particles, including protein complexes, cells, and viruses, is limited due to a high energy barrier, up to millions kT, required to detach particles from the interface, which is in dramatic contrast to a few kT for small molecules. Such a strong interaction renders particle adsorption quasi-irreversible. The dynamic adsorption-desorption equilibrium is approached very slowly, if ever attainable. This limitation is alleviated with a local oscillating repulsive mechanical force generated at the microstructured stimuli-responsive polymer interface to switch between adsorption and mechanical-force-facilitated desorption of the particles. Such a dynamic regime enables the separation of colloidal mixtures based on the particle-polymer interface affinity, and it could find use in research, diagnostics, and industrial-scale label-free sorting of highly asymmetric mixtures of colloids and cells.

The Shielding Effect of Microcrystalline Cellulose on Drug Nanocrystal Particles During Compaction.

To elucidate the compaction behavior of drug nanocrystals based composite particles (NP) during tabletting, the compaction behavior of binary mixtures of microcrystalline cellulose (MCC) and nanocrystal particles was investigated. The force-displacement correlation of mixtures containing different ratios of MCC and micronized NP was studied in order to explain the nature on densification of NP during compaction, and the resultant compaction curves (pressure as function of in-die thickness) were systemically analyzed to elucidate the most important mechanisms of volume reduction for MCC and NP in different stages of compaction. The results showed that the close compaction of individual MCC was relatively quickly achieved, and the drug NP particles could slide into the intrinsic void spaces between MCC microparticles. This was the reason that the particles size of MCC used in this study was significantly larger compared to that of drug NP. This interstitial rearrangement phenomenon of NP occurred on a typical time scale and was strongly dependent on the speed of compaction. This migration behavior occurred on void spaces of MCC inter-particles might be identified as an elastic stress relaxation mechanism and be helpful to dissolution of NP. MCC can effectively shield the NP from significant aggregation during compaction process.

Porous Stimuli-Responsive Self-Folding Electrospun Mats for 4D Biofabrication.

We report fabrication and characterization of electrospun, porous multi-layer scaffolds based-on thermo-responsive polymers polycaprolactone (PCL) and poly(N-isopropylacrylamide). We found that the electrospun mats fold into various 3D structures in an aqueous environment at different temperatures. We could determine the mechanism behind different folding behaviors under different conditions by consideration of the properties of the individual polymers. At 37 °C in an aqueous environment, the scaffolds spontaneously rolled into tubular structures with PCL as the inner layer, making them suitable for cell encapsulation. We also demonstrated that the cell adhesion and viability could be improved by coating the polymers with collagen, showing the suitability of this scaffold for several tissue engineering applications.

Computational design and fabrication of core-shell magnetic molecularly imprinted polymer for dispersive micro-solid-phase extraction coupled with high-performance liquid chromatography for the determination of rhodamine 6G.

A novel core-shell magnetic nano-adsorbent with surface molecularly imprinted polymer coating was fabricated and then applied to dispersive micro-solid-phase extraction followed by determination of rhodamine 6G using high-performance liquid chromatography. The molecularly imprinted polymer coating was prepared by copolymerization of dopamine and m-aminophenylboronic acid (functional monomers), in the presence of rhodamine 6G (template). The selection of the suitable functional monomers was based on the interaction between different monomers and the template using the density functional theory. The ratios of the monomers to template were further optimized by an OA9 (3(4) ) orthogonal array design. The binding performances of the adsorbent were evaluated by static, kinetic, and selective adsorption experiments. The results reveal that the adsorbent possesses remarkable affinity and binding specificity for rhodamine 6G because of the enhanced Lewis acid-base interaction between the B(Ш) embedded in the imprinted cavities and the template. The nano-adsorbent was successfully applied to dispersive micro-solid-phase extraction coupled to high-performance liquid chromatography for the trace determination of rhodamine 6G in samples with a detection limit of 2.7 nmol/L. Spiked recoveries ranged from 93.0-99.1, 89.5-92.7, and 86.9-105% in river water, matrimony vine and paprika samples, respectively, with relative standard deviations of less than 4.3%.

[Determination of degree of polymerization of natural cellulose pulp using near-infrared diffuse reflectance spectroscopy].

A new method of near-infrared (NIR) diffuse reflectance spectroscopy is proposed to rapidly determine the degree of polymerization (DP) of natural cellulose (cotton and wood) pulp produced by a new clean pulping process. One hundred and ninety five samples were collected and their DP data were determined by standard method GB/T 9107-1999. The spectroscopy measurement method of the samples was studied and their near-infrared diffuse reflectance spectra were collected. The quantitative DP calibration models of one mixed cotton & wood and two separate cotton and wood pulps were established by partial least squares (PLS). The optimum models were developed using the spectra pretreated by derivative, autoscaling and mean-centering, and their performance is as follows: correlation coefficient of 0.980, 0.993 and 0.886, and RMSEP of 147, 143 and 53, respectively. The accuracy of NIR method was also studied. The results show that the accuracy of the two separate models of cotton and wood is better than that of the mixed model, and the precision of the two separate models is better than that of GB/T9107-1999. The identification model of cotton and wood was also established using principal component analysis (PCA). The result shows that the spectra of cotton and wood pulp have obvious difference, and the model can identify successfully the two kinds of pulp. The result indicates that the new NIR method is feasible to realize the on-line analysis of polymerization degree of natural cellulose pulp with its advantage of rapidness and easy operation.

[Determination of alpha-cellulose content of natural cellulose pulp in a new clean pulping process using near infrared diffuse reflectance spectroscopy].

A new near infrared diffuse reflectance spectroscopy method is proposed to rapidly detect alpha-cellulose content of natural cellulose (plant fiber: cotton, wood) pulp in a new clean pulping process. One hundred forty two samples were collected and their alpha-cellulose content data were determined by standard method GB/T 9107-1999. The samples were homogenized by grinding pretreatment to improve spectroscopy measurement accuracy. Effective classification models were built by SIMCA, with the total correct identification. Using partial least squares (PLS) quantitative calibration, alpha-cellulose of the whole and separate cotton and wood pulp was established, with the correlation coefficients of 0.954, 0.911, 0.839, SEP, 0.024, 0.012 and 0.016, respectively. The repeatability results obtained by the new method are in agreement with the results from GB/T 9107-1999. The new method is feasible for determining alpha-cellulose content of natural cellulose (plant fiber: cotton, wood) in clean pulping process.

Response of preosteoblasts on micromachined Ti-6Al-4V surface to microstructure dimension.

The cell incubation depends on the cultured surface, but various machining methods produce different surface topographies, but it has not been clear how it is related to the topographic feature until now. Hence, the machined Ti-6Al-4V surface is characterized for preosteoblasts incubation via different mechanical fabrication. The relationship between surface topography created by various machining methods and cell incubation behaviour was explored. The objective is to control the surface preosteoblasts growth in machining of biological titanium alloy. According to the cell growth kinetic, the cell incubation behaviour was first proposed and modelled in relation to microstructural dimension and culture duration. Then, the topological cultured microstructure surface was fabricated via mechanical fabrication. Finally, the cell initial adhesion and incubation behaviour on microstructured surface was investigated. It is shown that the surface undulation on machined microstructure is conducive to controlling the direction and distribution of cell incubation from cell growth kinetic model. The cell culture can be controlled on the peak with a small undulation, while it is concentred on the sidewall with a high aspect ratio. Increasing the aspect ratio extends cell growth, while low aspect ratio promotes initial cell adhesion and growth rate. Within the optimal cultured duration, the microstructured surface is more favourable for cell survival, and the cell growth keep positive beyond critical aspect ratio. As a result, the cell adhesion ability is topologically controlled to 5.4 times higher and the growth rate can be improved by 101.7% on milled microgrooved surface. It may be applied to the rapid production of biomedical Ti-6Al-4V implant.

The material basis of astringency and the deastringent effect of polysaccharides: A review.

Astringency is a feeling of dryness in the mouth. Microscopically, it is manifested in the diversity of ingredients and mechanisms that can cause astringency, astringent components are mainly flavonoids, phenolic acids, tannin and other polyphenols components. Macroscopically, it is manifested in the rich variety of foods with astringent taste, because polyphenols are common secondary metabolites of plants. With the improvement of people's living standards, the demand for reducing or removing astringency in food and medicine is also increasing, and polysaccharides, as commonly used flavoring agents and food additives, have become the ideal choice for decreasing astringency. In this paper, the material basis, molecular mechanism, possible pathways and related cases of polysaccharides moderating of astringency are mainly reviewed, so as to illustrate the feasibility of polysaccharides decreasing of astringency and provide a reference for reducing the astringency of food and drugs.

The Oral Microbiome as Mediator between Oral Hygiene and Its Impact on Nasopharyngeal Carcinoma.

Oral hygiene and the alteration of the oral microbiome have been linked to nasopharyngeal carcinoma (NPC). This study aimed to investigate whether the oral microbiome plays a mediating role in the relationship between oral hygiene and NPC, and identify differential microbial taxonomies that potentially mediated this association. We conducted a case-control study that involved 218 NPC patients and 192 healthy controls. The 16S rRNA gene sequencing of the V4 region was performed to evaluate the composition of the oral microbiome. Mediation analysis was applied to explore the relationship among oral hygiene, the oral microbiome and NPC. We found that dental fillings and poor oral hygiene score were associated with increased risks of NPC (OR = 2.51 (1.52-4.25) and OR = 1.54 (1.02-2.33)). Mediation analysis indicated that dental fillings increased the risk of NPC by altering the abundance of Erysipelotrichales, Erysipelotrichaceae, Solobacterium and Leptotrichia wadei. In addition, Leptotrichia wadei also mediated the association between oral hygiene score and the risk of NPC. Our study confirmed that poor oral hygiene increased the risk of NPC, which was partly mediated by the oral microbiome. These findings might help us to understand the potential mechanism of oral hygiene influencing the risk of NPC via the microbiome.

N-Alkyl-PEI-functionalized iron oxide nanoclusters for efficient siRNA delivery.

Small-interfering RNA (siRNA) is an emerging class of therapeutics, which works by regulating the expression of a specific gene involved in disease progression. Despite the promises, effective transport of siRNA with minimal side effects remains a challenge. In this study, a nonviral nanoparticle gene carrier is developed and its efficiency for siRNA delivery and transfection is validated at both in vitro and in vivo levels. Such a nanocarrier, abbreviated as Alkyl-PEI2k-IO, was constructed with a core of iron oxide nanoparticles (IOs) and a shell of alkylated polyethyleneimine of 2000 Da [corrected] molecualr weight (Alkyl-PEI2k). It is found to be able to bind with siRNA, resulting in well-dispersed nanoparticles with a controlled clustering structure and narrow size distribution. Electrophoresis studies show that the Alkyl-PEI2k-IOs could retard siRNA completely at N:P ratios (i.e., PEI nitrogen to nucleic acid phosphate) above 10, protect siRNA from enzymatic degradation in serum, and release complexed siRNA efficiently in the presence of polyanionic heparin. The knockdown efficiency of the siRNA-loaded nanocarriers is assessed with 4T1 cells stably expressing luciferase (fluc-4T1) and further, with a fluc-4T1 xenograft model. Significant down-regulation of luciferase is observed, and unlike high-molecular-weight analogues, the Alkyl-PEI2k-coated IOs show good biocompatibility. In conclusion, Alkyl-PEI2k-IOs demonstrate highly efficient delivery of siRNA and an innocuous toxic profile, making it a potential carrier for gene therapy.

Nose-to-brain delivery of drug nanocrystals by using Ca2+ responsive deacetylated gellan gum based in situ-nanogel.

The objective of this study is to use a carbohydrate polymer deacetylated gellan gum (DGG) as matrix to design nanocrystals based intranasal in situ gel (IG) for nose-to -brain delivery of drug. The harmine nanocrystals (HAR-NC) as model drug were prepared by coupling homogenization and spray-drying technology. The HAR-NC was redispersed in the (DGG) solutions and formed the ionic-triggered harmine nanocrystals based in situ gel (HAR-NC-IG). The crystal state of HAR remained unchanged during the homogenization and spray-drying. And the HAR-NC-IG with 0.5% DGG exhibited excellent in situ-gelation ability, water retention property and in vitro release behavior. The bioavailability in brain of intranasal HAR-NC-IG were 25-fold higher than that of oral HAR-NC, which could be attributed to nanosizing effect of HAR-NC and bioadhesive property of DGG triggered by nasal fluid. And the HAR-NC-IG could significantly inhibit the expression of acetylcholinesterase (AchE) and increase the content of acetylcholin (ACh) in brain compared with those of reference formulations (p < 0.01). The DGG based nanocrystals-in situ gel was a promising carrier for nose-to-brain delivery of poorly soluble drug, which could prolong the residence time and improve the bioavailability of poorly soluble drugs in brain.

In vivo tumor-targeted fluorescence imaging using near-infrared non-cadmium quantum dots.

This article reported the high tumor targeting efficacy of RGD peptide labeled near-infrared (NIR) non-cadmium quantum dots (QDs). After using poly(ethylene glycol) to encapsulate InAs/InP/ZnSe QDs (emission maximum at about 800 nm), QD800-PEG dispersed well in PBS buffer with the hydrodynamic diameter (HD) of 15.9 nm and the circulation half-life of approximately 29 min. After coupling QD800-PEG with arginine-glycine-aspartic acid (RGD) or arginine-alanine-aspartic acid (RAD) peptides, we used nude mice bearing subcutaneous U87MG tumor as models to test tumor-targeted fluorescence imaging. The results indicated that the tumor uptake of QD800-RGD is much higher than those of QD800-PEG and QD800-RAD. The semiquantitative analysis of the region of interest (ROI) showed a high tumor uptake of 10.7 +/- 1.5%ID/g in mice injected with QD800-RGD, while the tumor uptakes of QD800-PEG and QD800-RAD were 2.9 +/- 0.3%ID/g and 4.0 +/- 0.5%ID/g, respectively, indicating the specific tumor targeting of QD800-RGD. The high reproducibility of bioconjunction between QDs and the RGD peptide and the feasibility of QD-RGD bioconjugates as tumor-targeted fluorescence probes warrant the successful application of QDs for in vivo molecular imaging.

Nose-to-Brain Delivery by Nanosuspensions-Based in situ Gel for Breviscapine.

PURPOSE: Nose-to-brain drug delivery is an effective approach for poorly soluble drugs to bypass the blood-brain barrier. A new drug intranasal delivery system, a nanosuspension-based in situ gel, was developed and evaluated to improve the solubility and bioavailability of the drug and to prolong its retention time in the nasal cavity. MATERIALS AND METHODS: Breviscapine (BRE) was chosen as the model drug. BRE nanosuspensions (BRE-NS) were converted into BRE nanosuspension powders (BRE-NP). A BRE nanosuspension in situ gelling system (BRE-NG) was prepared by mixing BRE-NP and 0.5% gellan gum (m/v). First, the BRE-NP were evaluated in terms of particle size and by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Subsequently, the critical ionic concentration of the gellan gum phase transition, influence of the deacetylated gellan gum (DGG) concentration on the expansion coefficient (S%), water-holding capacity, rheological properties and in vitro release behaviour of the BRE-NG were investigated. The pharmacokinetics and brain distribution of the BRE-NG after intranasal administration were compared with those of the intravenously injected BRE-NP nanosuspensions in rats. RESULTS: The rheology results demonstrated that BRE-NG was a non-Newtonian fluid with good spreadability and bioadhesion performance. Moreover, the absolute bioavailability estimated for BRE-NG after intranasal administration was 57.12%. The drug targeting efficiency (DTE%) of BRE in the cerebrum, cerebellum and olfactory bulb was 4006, 999 and 3290, respectively. The nose-to-brain direct transport percentage (DTP%) of the cerebrum, cerebellum and olfactory bulb was 0.975, 0.950 and 0.970, respectively. CONCLUSION: It was concluded that the in situ gel significantly increased the drug retention time at the administration site. Therefore, the nanosuspension-based in situ gel could be a convenient and effective intranasal formulation for the administration of BRE.

Interplay of Nanoparticle Rigidity and Its Translocation Ability through Cell Membrane.

Understanding the endocytic process of nanoparticles (NPs) with different mechanical rigidities is critical to develop effective drug delivery vectors. Here, we perform experiments, coarse-grained molecular dynamics simulations, and theoretical analyses to investigate the role of NPs' mechanical rigidity in the cellular endocytic process. Experiments based on two types of engineered Au NPs that have similar properties but different rigidities are performed in order to investigate their cellular uptake efficiencies, and it has been found that the more rigid NPs can achieve a higher cellular uptake efficiency. Simulation results confirm that rigid NPs can achieve full internalization by forming a complete double-layer endosome coating, while relatively soft NPs can only reach 40% surface coverage by membrane lipids. Simulation results capture an intriguing translocation of multiple NPs with different rigidities in a cooperative manner where the NPs' mechanical rigidities regulate their translocation efficiencies. We find that theoretically rigid NPs require less energy to overcome the energy barrier for membrane internalization than soft NPs do, which is in good agreement with experiment and simulation results. This synergetic study offers useful insight into the design principle of a general NP-based drug delivery vector as well as the promising biomedical application of NP-based medicine.

Novel redispersible nanosuspensions stabilized by co-processed nanocrystalline cellulose-sodium carboxymethyl starch for enhancing dissolution and oral bioavailability of baicalin.

BACKGROUND: To improve the dissolution and bioavailability of poorly soluble drugs, novel nanosuspensions using co-processed nanocrystalline cellulose-sodium carboxymethyl starch (NCCS) as a synergetic stabilizer were first designed. METHODS: Co-processed NCCS was prepared by means of homogenization. Poorly soluble baicalin (BCA) was used as a model drug. BCA nanosuspension (BCA-NS/NCCS) using co-processed NCCS as a dispersant was prepared via homogenization and further converted into the dried BCA nanosuspension particle (BCA-NP/NCCS) via spray drying. The influence of NCCS on the dispersion efficiency of BCA-NS/NCCS was investigated. Morphology and crystal characteristic of NCCS and BCA-NP were analyzed. The dissolution and bioavailability evaluation were performed to investigate the feasibility of NCCS as a stabilizer for BCA-NS/NCCS and BCA-NP. RESULTS: The optimum 50% concentration of NCCS (nanocrystalline cellulose [NCC]:sodium carboxymethyl starch [SCS]=60:40) could be mostly beneficial for formation and stability of BCA-NS/NCCS. NCCS could completely prevent aggregation of BCA-NP during spray drying and enhance the redispersibility as well as dissolution of spray-dried BCA-NP, which might be attributed to "brick-concrete"-based barrier effect of NCCS and the swelling capacity of superdisintegrant SCS. The crystal state of NCC and BCA presented in BCA-NP/NCCS remained unchanged during the homogenization. The BCA-NP/NCCS exhibited a fast dissolution rate and significantly enhanced bioavailability of BCA. The AUC(0-∞) of the BCA-NP/NCCS (8,773.38±718.18 µg/L·h) was 2.01 times (P<0.05) as high as that of the crude BCA (4,354.61±451.28 µg/L·h). CONCLUSION: This study demonstrated that novel surfactant-free nanosuspensions could be prepared using co-processed NCCS as a synergetic stabilizer and also provided a feasible strategy to improve the dissolution and oral bioavailability of poorly soluble drug.

Redispersible Pickering emulsion powder stabilized by nanocrystalline cellulose combining with cellulosic derivatives.

The objective of this study is to use cellulose nanocrystals (CNC) combining with carboxymethyl cellulose sodium (CMC-Na) and hydroxypropyl methylcellulose (HPMC) as stabilizer to prepare novel redispersible camellia oil Pickering emulsions powder (CO-PEP). Cellulose nanocrystals modified with carboxymethyl cellulose sodium (CNCC) was prepared by homogenization technology. CNCC seemed to be rod-like particles with mean particle size of 124.2 ± 2.5 nm. And the cellulose structure, crystal state and thermal property of CNCC remained unchanged during the homogenization. The combination of CNC and CMC-Na in CNCC might be dependent of physical interaction. The mean particle size of optimum CO-PE/0.25%CNCC was 0.569 ± 0.023 µm. The CNCC based particle stabilizer might form the distinctive barrier layer around oil droplet. The redispersibility results demonstrated that 50% HPMC based CO-PEP formed large composite particle with high drug loading ability and exhibited superior redispersibility. Novel redispersible powdered Pickering emulsions could be prepared by cellulose nanocrystals combining with water-soluble cellulosic derivatives.

pH controlled release of chromone from chromone-Fe3O4 nanoparticles.

We report a new strategy for coupling chromone to Fe3O4 nanoparticles. The chromone-Fe3O4 NP conjugate shows a dramatic increase in chromone solubility in cell culture medium from less than 2.5 to 633 microg/ml, leading to the enhanced chromone uptake by HeLa cells. Chromone can be released at low pH and as a result, the chromone-Fe3O4 conjugate is much more efficient in inhibiting the HeLa cell proliferation. Such chromone-Fe3O4 NPs are promising as a powerful multifunctional delivery system for both chromone-based diagnostic and therapeutic applications.