We investigated the effect of reaction temperature on the particle size and morphology of hydroxy zinc phosphate particles (HZnPPs). The influence of differences in shape on the physiochemical properties of HZnPPs and the possible bioapplications of these particles were also investigated. HZnPPs with both hollow and solid nanospheres and microsized rectangular sheet-like particles were successfully prepared by a wet chemical method using Zn (NO3)2·6H2O and (NH4)2HPO4 as the reactants and ammonia to adjust the pH. The synthesis was performed at temperatures ranging from 0 to 95 °C. The particle size, morphology, crystal structure and thermal properties were analysed by X-ray diffraction, scanning electron microscopy, transmission electron microscopy, the Brunauer–Emmett–Teller specific surface area, thermogravimetric analysis and dynamic light scatting. The chemical composition and vibrational spectra were measured using inductively coupled plasma atomic emission spectrometry, Fourier transform infrared spectrometry and Raman spectrometry. The transmission electron microscopy results showed that a hollow spherical structure with a pore size of 20–30 nm was obtained at reaction temperatures <25 °C. With increasing temperature, the nanoparticles changed from hollow to solid spheres of a similar size. Microsized rectangular sheet-like particles were formed when the reaction temperature was >60 °C. The effect of HZnPPs on cell viability in vitro was evaluated by the MTT assay against normal NIH/3T3 cells. The hollow and solid nanospheres had a lower cell cytotoxicity than the microsized sheet-like particles. Both the nanospheres and the rectangular sheet-like particles were able to adsorb heavy metal ions. The hollow nanospheres were also used as a carrier for a high drug-loading of epirubicin. These results clearly show that temperature plays an important part in regulating the nanoscale hierarchical structure of HZnPPs and their properties.

Micro-computed tomography (micro-CT) is a powerful tool for visualizing the vascular systems of tissues, organs, or entire small animals. Vascular contrast agents play a vital role in micro-CT imaging in order to obtain clear and high-quality images. In this study, a new kind of nanostructured barium phosphate was fabricated and used as a contrast agent for ex vivo micro-CT imaging of blood vessels in the mouse brain. Nanostructured barium phosphate was synthesized through a simple wet precipitation method using Ba(NO3)2, and (NH4)2HPO4 as starting materials. The physiochemical properties of barium phosphate were characterized by scanning electron microscopy, transmission electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, and thermal analysis. Furthermore, the impact of the produced nanostructures on cell viability was evaluated via the MTT assay, which generally showed low to moderate cytotoxicity. Finally, the animal test images demonstrated that the use of nanostructured barium phosphate as a contrast agent in Micro-CT imaging produced sharp images with excellent contrast. Both major vessels and the microvasculature were clearly observable in the imaged mouse brain. Overall, the results indicate that nanostructured barium phosphate is a potential and useful vascular contrast agent for micro-CT imaging.

Magnesium-doped hydroxyapatites (Mg-HAs) with different feeding molar ratios of Ca:Mg were synthesized by a wet-chemical method at 90 °C based on the step reaction and ion exchange processes. Firstly, magnesium nitrate (Mg(NO3)2·6H2O) and diammonium hydrogen phosphate ((NH4)2HPO4) with a Mg:P molar ratio of 1.67 were used as starting materials and ammonia water was used as the agent for pH adjustment. Perfect long hexagon shape plates 4–10 μm in size with 200–300 nm thickness were obtained. These particles were then used as precursors, and calcium nitrate (Ca(NO3)2·4H2O) solutions with feeding Ca:Mg molar ratios of 2.5:1, 5:1, 7.5:1, 10:1, 12.5:1, and 15:1 were added, followed by the addition of (NH4)2HPO4. The (Ca + Mg):P molar ratio was kept at 1.67 during the reaction process. Magnesium ions in the precursor particles were substituted by calcium ions during the process of ion exchange in solution. As a result, the particle size (ranging from nano- to micro-scale), morphology, and magnesium content (1.3–4.2 wt%) in the final Mg-HAs were well controlled by the precursor particles and the original addition of different Ca:Mg molar ratios. The transmission electron microscopy (TEM) images showed the morphology changes with different Ca:Mg feeding ratios. The X-ray powder diffraction (XRD) analysis showed that the lattice disorder increased with Mg substitution in the hydroxyapatite. The (Ca + Mg):P molar ratio, chemical properties, and thermal stability properties were investigated by inductively coupled plasma emission spectrometry (ICP), Fourier transform infrared spectroscopy (FTIR), and thermal gravimetric analysis (TGA), respectively. In addition, methyl-thiotetrazole (MTT) assay demonstrated that the Mg-HA materials exhibited quite low cytotoxicity. The formation mechanism of the Mg-HA particles could be explained by a precursor particle template and ion exchange process. The present work provides a novel approach to prepare well-controlled Mg-doped HA nanoparticles.

Hollow hydroxy zinc phosphate nanospheres (HZnPNSs) with sizes of 30–50 nm and wall thicknesses of about 7 nm were synthesized using a template-free method through wet precipitation of Zn(NO3)2·6H2O and (NH4)2HPO4 at temperatures of 0, 10, and 20 °C. The crystal structures, morphologies, sizes and pore properties, Zn/P molar ratios, and thermal stability properties of nanoparticles have been carefully examined. The methyl-thiotetrazole assay measurements proved the low cell cytotoxicity of the material. The protein adsorption of negatively charged bovine serum albumin (BSA) and positively charged lysozyme on HZnPNSs was also investigated. The results showed that HZnPNSs had high protein adsorption affinity. Furthermore, anticancer doxorubicin as a model drug was used to evaluate the entrapment efficiency and drug loading capacity of HZnPNSs, which showed high loading capacity (>16 wt %) for doxorubicin. The confocal laser scanning microscope observations showed that the drug could be efficiently delivered into cells.

Chlorin e6 (Ce6), a big heterocyclic aromatic molecule, is considered promising photosensitizer for photodynamic therapy (PDT). Here an efficient nano-photosensitizer delivery system based on noncovalent interactions between Ce6 and single wall carbon nanotubes (SWCNTs) is proposed. By utilization of high surface area of SWCNTs, Ce6 was loaded on them with a high drug loading content by noncovalent π–π interactions. Then, the Ce6–SWCNT complexes were wrapped by chitosan to improve aqueous solubility and biocompatibility. The chemical characteristics of Ce6–SWCNTs and chitosan–Ce6–SWCNTs were evaluated by different analysis methods, including transmission electron microscopy, UV–Visible absorption spectra, and Fourier transform infrared spectra. The high cellular uptake of chitosan–Ce6–SWCNTs was confirmed by flow cytometry and confocal laser scanning microscopy. According to the WST-1 assay, the chitosan–Ce6–SWCNTs exhibited low dark toxicity and efficient PDT efficacy to HeLa cancer cells. These results indicate that chitosan–Ce6–SWCNTs are a potential photosensitizer delivery system for PDT.

The architecture of conjugated polymers has an important influence on their optical and electrical properties. In this study, the effect of branching architecture on the optical properties of polyazomethines (PAs) was investigated. Linear and branched PAs with degree of branching (DB) ranging from 0 to 0.52 were successfully synthesized through homogeneous condensation by changing the feeding ratios of diamine, tetramine and dialdehyde. All PAs showed good thermal stability, and their decomposition temperature was over 380 °C. Both UV-Vis absorption and fluorescence emission demonstrated that the optical properties of PAs were closely related to the DB. With the increase of DB, an obvious redshift was found in UV-Vis absorption spectra, and the fluorescence maximum emission intensity (FMEI) and relative fluorescence quantum efficiency (RFQE) initially increased to a maximum and then gradually diminished to almost zero. These phenomena could be attributed to the antagonistic effect between the auxochromic effect of amino groups and the intra- and inter-molecular interactions. To confirm this mechanism, the intra- and inter-molecular interactions were purposely broken by adding trifluoroacetic acid (TFA) and SnCl2, which resulted in an increase in FMEI. Therefore, the optical properties of conjugated polymers can be readily adjusted by changing the DB of polymers.

Janus-type dendritic poly(amido amine) (PAMAM) amphiphiles Dm-Lac-D3DNQ were synthesized by connecting hydrophobic diazonaphthoquinone (DNQ)-decorated PAMAM dendron D3 (generation 3) and hydrophilic lactose (Lac)-decorated PAMAM dendrons Dm (generations 0–2, m = 0–2) via click chemistry. They self-assembled into the DNQ-cored micelles dangled by densely free Lac groups in aqueous solution. Irradiated by 808 nm laser and 365 nm lamp, both NIR- and UV-sensitivity of micelles were characterized by time-resolved UV–vis spectroscopy. The characteristic absorption intensity of DNQ progressively decreased and then leveled off. Moreover, the bigger the micelles, the more the irradiation time for finishing Wolff rearrangement of DNQ. TEM further confirmed that most of the micelles disassembled after 30 min of 808 nm laser irradiation. The Lac-coated micelles showed binding with RCA120 lectin, as monitored by UV–vis and DLS. The apparent drug-release rate of doxorubicin (DOX) loaded nanomedicine nearly doubled after 10 min of 808 nm laser irradiation, presenting a NIR-triggered drug-release profile. Moreover, the DOX-loaded nanomedicine presented a phototriggered cytotoxicity that was close to free DOX, and they could quickly enter into HeLa cells, as evidenced by MTT assay, flow cytometry, and CLSM. Importantly, this work provides a versatile strategy for the fabrication of NIR-responsive and lectin-binding dendrimer nanomedicine, opening a new avenue for “on-demand” and spatiotemporal drug delivery.

Polymeric drug carriers with high stability during long circulation and triggered degradation after drug release are particularly interesting in drug delivery. Here, a novel pH-triggered backbone-cleavable hyperbranched polyacylhydrazone (HPAH) was successfully prepared through a simple polycondensation of 2,3-butanedione and 1-(2-aminoethyl) piperazine tri-propionylhydrazine. The experimental results showed that the degree of branching (DB) of HPAH was 0.60, and the weight-average molecular weight (Mw) of end-capped HPAH was 4.0 × 103 with a polydipersity index (PDI) of 1.6. 2D DOSY NMR degradation experiments demonstrated that HPAH was stable in neutral conditions while cleavable in acidic environments. Owing to the existence of numerous acylhydrazine terminals, the anticancer drug doxorubicin (DOX) was conjugated to hydrophilic HPAH. The obtained HPAH-DOX conjugate could self-assemble into polymeric micelles with an average diameter of 20 nm, which were stable under physiological pH but cleavable after endocytosis. Cell viability of HPAH, monomers, and degradation products was maintained above 70% over the culture periods, even when the concentration was up to 3 mg mL−1 according to methyl tetrazolium (MTT) assay in NIH/3T3 cell line. Both flow cytometry and confocal laser scanning microscopy (CLSM) confirmed the high cellular uptake of HPAH-DOX. Anti-cancer effect was evaluated in HeLa cell line, and the DOX dose required for 50% cellular growth inhibition was found to be 3.5 μg mL−1 by MTT assay.

Novel supramolecular copolymer micelles with stimuli-responsive abilities were successfully prepared through the complementary multiple hydrogen bonds of nucleobases and then applied for rapid intracellular release of drugs. First, both adenine-terminated poly(ε-caprolactone) (PCL-A) and uracil-terminated poly(ethylene glycol) (PEG-U) were synthesized. The supramolecular amphiphilic block copolymers (PCL-A:U-PEG) were formed based on multiple hydrogen bonding interactions between PCL-A and PEG-U. The micelles self-assembled from PCL-A:U-PEG were sufficiently stable in water but prone to fast aggregation in acidic condition due to the dynamic and sensitive nature of noncovalent interactions. The low cytotoxicity of supramolecular copolymer micelles was confirmed by MTT assay against NIH/3T3 normal cells. As a hydrophobic anticancer model drug, doxorubicin (DOX) was encapsulated into these supramolecular copolymer micelles. In vitro release studies demonstrated that the release of DOX from micelles was significantly faster at mildly acid pH of 5.0 compared to physiological pH. MTT assay against HeLa cancer cells showed DOX-loaded micelles had high anticancer efficacy. Hence, these supramolecular copolymer micelles based on the complementary multiple hydrogen bonds of nucleobases are very promising candidates for rapid controlled release of drugs.

Oxime bonds dispersed in the backbones of the synthetic polymers, while young in the current spectrum of the biomedical application, are rapidly extending into their own niche. In the present work, oxime linkages were confirmed to be a robust tool for the design of pH-sensitive polymeric drug delivery systems. The triblock copolymer (PEG-OPCL-PEG) consisting of hydrophilic poly(ethylene glycol) (PEG) and hydrophobic oxime-tethered polycaprolactone (OPCL) was successfully prepared by aminooxy terminals of OPCL ligating with aldehyde-terminated PEG (PEG-CHO). Owing to its amphiphilic architecture, PEG-OPCL-PEG self-assembled into the micelles in aqueous media, validated by the measurement of critical micelle concentration (CMC). The MTT assay showed that PEG-OPCL-PEG exhibited low cytotoxicity against NIH/3T3 normal cells. Doxorubicin (DOX) as a model drug was encapsulated into the PEG-OPCL-PEG micelles. Drug release study revealed that the DOX release from micelles was significantly accelerated at mildly acid pH of 5.0 compared to physiological pH of 7.4, suggesting the pH-responsive feature of the drug delivery systems with oxime linkages. Flow cytometry and confocal laser scanning microscopy (CLSM) measurements indicated that these DOX-loaded micelles were easily internalized by living cells. MTT assay against HeLa cancer cells showed DOX-loaded PEG-OPCL-PEG micelles had a high anticancer efficacy. All of these results demonstrate that these polymeric micelles self-assembled from oxime-tethered block copolymers are promising carriers for the pH-triggered intracellular delivery of hydrophobic anticancer drugs.

A double-hydrophilic multiarm hyperbranched polymer with a hyperbranched poly(amidoamine) (HPAMAM) core and many poly(ethylene glycol) monomethyl ether (MPEG) arms connected by pH-sensitive acylhydrazone bonds (HPAMAM-g-MPEG) was successfully prepared. Benefiting from the cationic dendritic core and PEGylation shell, the double-hydrophilic multiarm hyperbranched polymer was used as a nanoreactor for CdS quantum dots (CdS QDs) synthesis in aqueous solution. The obtained HPAMAM-g-MPEG and CdS/HPAMAM-g-MPEG nanocomposites were carefully characterized by 1H NMR, 13C NMR, Fourier transform infrared spectroscopy (FTIR), ultraviolet−visible absorption spectroscopy (UV−vis), fluorescence spectroscopy (FL), dynamic light scattering (DLS), transmission electron microscopy (TEM), selected area electron diffraction (SAED), and electronic dispersive X-ray spectroscopy (EDS) analysis. Both 1H NMR and fluorescence spectroscopy investigations confirmed that the acylhydrazone linkage between the dendritic core and linear arms was readily broken under acidic condition (pH <5.5). When MPEG arms departed from the HPAMAM core, the fluorescence intensity of CdS/HPAMAM-g-MPEG nanocomposites greatly increased. Such pH-responsive behavior of CdS/HPAMAM-g-MPEG nanocomposites was utilized as an exploration of a novel fluorescence probe in an acidic lysosome exemplified by COS-7 cells.

Novel cationic drug carriers based on hyperbranched poly(amine-ester)s were successfully prepared through proton-transfer polymerization. Both vinyl and epoxy groups of commercially available glycidyl methacrylate monomer could be polymerized through oxyanionic initiation of triethanolamine in the presence of potassium hydride catalysis. By changing the molar ratios of triethanolamine/glycidyl methacrylate or potassium hydride/triethanolamine, we obtained a series of hyperbranched poly(amine-ester)s. The generation of highly branched poly(amine-ester)s was confirmed by 13C DEPT-135 NMR and 2D NMR techniques, and their degrees of branching were found to be 0.47 to 0.68. The structure and properties of hyperbranched poly(amine-ester)s were analyzed by dynamic light scattering, gel permeation chromatography, Fourier transformed infrared, differential scanning calorimeter, and ζ-potential measurements. Methyl tetrazolium (MTT) assay suggested that the cell viability after 48 h incubation with hyperbranched poly(amine-ester) concentrations up to 1 mg/mL remained nearly 100% compared with the untreated cells. The high cellular uptake of these cationic polymers was confirmed by flow cytometry and confocal laser scanning microscopy. Furthermore, conjugation of a model hydrophobic anticancer drug chlorambucil to hyperbranched poly(amine-ester)s inhibited the proliferation of MCF-7 breast cancer cells. MTT assay indicated that the chlorambucil dose required for 50% cellular growth inhibition against MCF-7 cells was 120 μg/mL. All of these results show that hyperbranched poly(amine-ester)s are promising materials for drug delivery.

•Micro-/nanofibers prepared via co-assembly with paclitaxel and dextran.•Paclitaxel was interacted with dextran through non-covalent interactions.•The microfibers formed by twisted bundles of nanofibers.•The paclitaxel/dextran fibers had good performance in drug delivery.In this paper, we reported the preparation of micro-/nanofibers via co-assembly with paclitaxel (PTX) and dextran (DEX). The co-assembly fibers formed in PTX and DEX mixture solution via non-covalent interactions including hydrophilic/hydrophobic interactions and π-π stacking. The micro-/nanofibers could be obviously observed when the mixed solution became turbid and ivory-white in color. The properties of fibers were characterized by SEM, TEM, FTIR, DSC, XRD, in vitro release and MTT assay. The length of fibers could reach several centimeters. The diameter of microfibers and nanofibers was about 800 nm and 80 nm, respectively. In addition, the PTX loading efficiency was over 78% in co-assembly fibers and up to 84% when PTX and DEX (Mw: 40,000) both were 2 mg/mL. The sustained drug release and low cytotoxicity in vitro of PTX/DEX fibers were also demonstrated. Therefore, we believe that PTX/DEX micro-/nanofibers would have great potential for drug delivery of PTX.

We investigated the effect of reaction temperature on the particle size and morphology of hydroxy zinc phosphate particles (HZnPPs). The influence of differences in shape on the physiochemical properties of HZnPPs and the possible bioapplications of these particles were also investigated. HZnPPs with both hollow and solid nanospheres and microsized rectangular sheet-like particles were successfully prepared by a wet chemical method using Zn (NO3)2·6H2O and (NH4)2HPO4 as the reactants and ammonia to adjust the pH. The synthesis was performed at temperatures ranging from 0 to 95 °C. The particle size, morphology, crystal structure and thermal properties were analysed by X-ray diffraction, scanning electron microscopy, transmission electron microscopy, the Brunauer–Emmett–Teller specific surface area, thermogravimetric analysis and dynamic light scatting. The chemical composition and vibrational spectra were measured using inductively coupled plasma atomic emission spectrometry, Fourier transform infrared spectrometry and Raman spectrometry. The transmission electron microscopy results showed that a hollow spherical structure with a pore size of 20–30 nm was obtained at reaction temperatures <25 °C. With increasing temperature, the nanoparticles changed from hollow to solid spheres of a similar size. Microsized rectangular sheet-like particles were formed when the reaction temperature was >60 °C. The effect of HZnPPs on cell viability in vitro was evaluated by the MTT assay against normal NIH/3T3 cells. The hollow and solid nanospheres had a lower cell cytotoxicity than the microsized sheet-like particles. Both the nanospheres and the rectangular sheet-like particles were able to adsorb heavy metal ions. The hollow nanospheres were also used as a carrier for a high drug-loading of epirubicin. These results clearly show that temperature plays an important part in regulating the nanoscale hierarchical structure of HZnPPs and their properties.

A facile strategy for the construction of supramolecular star-shaped ABC terpolymer was proposed and realized via the molecular recognition between β-cyclodextrin- (β-CD-) based host and adamantane- (AD-)modified guest. In the first step, β-CD with two different functional groups was prepared, which was further used to construct a diblock copolymer host via “click” reaction with alkynyl-poly(ethylene glycol) (alkynyl-PEG) and atom transfer radical polymerization (ATRP) of dimethylaminoethyl methacrylate (DMAEMA) monomer. On the other hand, the AD-modified polymeric guest was obtained by ATRP of methyl methacrylate (MMA) using an AD-modified initiator. Because of the molecular recognition between β-CDs and adamantyl moieties, the polymeric host and guest formed a star-shaped ABC miktoarm terpolymer via a simple mixing procedure. The resultant ABC miktoarm star-shaped terpolymer was characterized by two-dimensional NMR spectroscopy. This amphiphilic ABC miktoarm terpolymer could self-assemble into micelles in aqueous solution, and the reversible transition between assembly and disassembly of this supramolecular ABC miktoarm star terpolymer could be readily controlled by adding the competitive host or guest.

Magnesium-doped hydroxyapatites (Mg-HAs) with different feeding molar ratios of Ca:Mg were synthesized by a wet-chemical method at 90 °C based on the step reaction and ion exchange processes. Firstly, magnesium nitrate (Mg(NO3)2·6H2O) and diammonium hydrogen phosphate ((NH4)2HPO4) with a Mg:P molar ratio of 1.67 were used as starting materials and ammonia water was used as the agent for pH adjustment. Perfect long hexagon shape plates 4–10 μm in size with 200–300 nm thickness were obtained. These particles were then used as precursors, and calcium nitrate (Ca(NO3)2·4H2O) solutions with feeding Ca:Mg molar ratios of 2.5:1, 5:1, 7.5:1, 10:1, 12.5:1, and 15:1 were added, followed by the addition of (NH4)2HPO4. The (Ca + Mg):P molar ratio was kept at 1.67 during the reaction process. Magnesium ions in the precursor particles were substituted by calcium ions during the process of ion exchange in solution. As a result, the particle size (ranging from nano- to micro-scale), morphology, and magnesium content (1.3–4.2 wt%) in the final Mg-HAs were well controlled by the precursor particles and the original addition of different Ca:Mg molar ratios. The transmission electron microscopy (TEM) images showed the morphology changes with different Ca:Mg feeding ratios. The X-ray powder diffraction (XRD) analysis showed that the lattice disorder increased with Mg substitution in the hydroxyapatite. The (Ca + Mg):P molar ratio, chemical properties, and thermal stability properties were investigated by inductively coupled plasma emission spectrometry (ICP), Fourier transform infrared spectroscopy (FTIR), and thermal gravimetric analysis (TGA), respectively. In addition, methyl-thiotetrazole (MTT) assay demonstrated that the Mg-HA materials exhibited quite low cytotoxicity. The formation mechanism of the Mg-HA particles could be explained by a precursor particle template and ion exchange process. The present work provides a novel approach to prepare well-controlled Mg-doped HA nanoparticles.