Carbonated Nano Hydroxyapatite Crystal Growth Modulated by Poly(ethylene glycol) with Different Molecular Weights

The effects of poly­(ethylene glycol) (PEG) molecular weights on nano hydroxyapatite (n-HA) crystal growth were studied, and a possible mechanism was proposed. n-HA crystals were synthesized in the presence of PEG with different molecular weights via hydrothermal method. Transmission electron microscopy (TEM) analysis showed that the presence of PEG increased the size of n-HA crystals; PEG with larger molecular weights produced larger n-HA crystals. High-resolution TEM observation indicated that all of the n-HA crystals tended to grow along the ⟨002⟩ axis. X-ray diffraction patterns showed that all of the samples consisted of only the HA phase. Besides, PEG increased the crystallinity of n-HA crystals, and this effect was more significant for PEGs with larger molecular weights. Fourier transform infrared results further revealed that all of the crystals were carbonated HA. Thermogravimetry/differential scanning calorimetry analysis detected PEG residues on n-HA particles. To thoroughly study the modulating mechanism of PEGs on n-HA crystal growth, n-HA samples heat-treated for various times were prepared in the presence of PEG20000, and a possible mechanism in which PEG modulated the growth of n-HA crystals was discussed

NIR-to-Red Upconversion Nanoparticles with Minimized Heating Effect for Synchronous Multidrug Resistance Tumor Imaging and Therapy

Lanthanide-doped upconversion nanoparticles (UCNPs), especially the 808 nm activated UCNPs, are promising imaging agents for biological applications because of their minimal tissue overheating effects and low autofluorescence background. Optimizing the emission peaks located in the “biological window (600–1100 nm)” is of vital importance to obtain the maximum penetration depth and intense deep tissue imaging. On the other hand, because of the widely existing multidrug resistance (MDR) of tumor cells, traditional tumor chemotherapy often fails to achieve the desired effect. Herein, a new type of 808 nm excited pure red luminescence core–shell Nd³⁺-sensitized NaY­(Mn)­F₄:Yb/Er@NaYbF₄:Nd UCNPs (CSUCNPs) was designed and synthesized for deep tissue imaging and MDR tumor diagnosis with a minimized heating effect. In the meanwhile, d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) coating was introduced to endow CSUCNPs with capabilities of drug loading and overcoming MDR. The in vitro cytotoxicity test revealed that CSUCNPs-TPGS-doxorubicin (D-CSUCT) had excellent MDR cancer cell killing efficacy. The in vivo test showed that D-CSUCT can target the tumor site by enhanced retention effect, and the intense luminescent signals from the tumor site in the deep tissue were detected. Generally, this work shows D-CSUCT can overcome the MDR effect, diagnose the tumor, inhibit tumor growth, and induce tumor cells necrosis and apoptosis, without causing damage to major organs and other side effects. Overall, the study demonstrates the conjugation of red-emitted UCNPs with a minimized heating effect and that the anti-MDR carrier is highly promising for developing multifunctional theranostic system with effective simultaneous diagnosis and for multidrug-resistant tumor treatment

Two-Step Nucleation of CdS Magic-Size Nanocluster MSC–311

Nucleation has been generally acknowledged as a rapid but uncontrollable process that is difficult to decouple from the subsequent growth phase. Here, we report our finding that nucleation of semiconductor magic-size clusters (MSCs) can be well-regulated, without a subsequent evolution in size. Colloidal semiconductor CdS MSCs were synthesized by a two-step approach intentionally designed, without the simultaneous formation of nanocrystals of other sizes. The nuclei MSCs exhibit a sharp optical absorption peaking at 311 nm and are thus denoted by MSC–311. We prepared the immediate precursor for MSC–311 denoted by IP311 which is liquid-like, through a reaction which was normally performed to grow CdS conventional quantum dots (QDs), but at a different temperature (180 °C) prior to the nucleation and growth of CdS QDs. We demonstrate that the nucleation of MSC–311 from IP311 followed first order kinetics remarkably well, and the presence of a small amount of methanol accelerated this process effectively. Moreover, the liquid-like prenucleation cluster IP311 and the nuclei MSC–311 have similar masses. Accordingly, we propose that the intramolecular reorganization of IP311 results in the nuclei MSC–311, the formation of which features a two-step nucleation pathway. The present study introduces methodology via absorption spectroscopy to monitor the nucleation kinetics of semiconductor MSCs from their immediate precursors. The repeatable, predictable, and controllable nucleation process investigated here brings a deeper insight into nucleation of other semiconductor nanocrystals and contributes to the foundation for the future development of advanced theoretical models for crystal nucleation

Colloidal CdSe 0‑Dimension Nanocrystals and Their Self-Assembled 2‑Dimension Structures

We report on a particular type of CdSe nanocrystals (NCs) that exhibit a single optical absorption doublet. The two peaks in the doublet are relatively sharp with a full width half-maximum as narrow as 10 nm. The peak positions vary with passivation ligands (at ∼426 and ∼453 nm for amine ligand passivation and at ∼432 and ∼460 nm for carboxylate ligand passivation). To date, it has been generally concluded that these NCs have a two-dimension (2D) morphology with 1D quantum confinement. Here, we report that zero-dimension (0D) NCs with 3D quantum confinement can exhibit a very similar static optical feature consisting of a sharp absorption doublet. We show that our as-prepared CdSe NCs (without further purification) were mainly 0D NCs, as observed when they were deposited on transmission electron microscopy (TEM) grids directly from toluene or hexane dispersions. We further demonstrate that it was possible to alter this 0D morphology by using dispersion additives and/or purification solvents to result in the appearance of 2D NCs under TEM. Although the 0D and self-assembled 2D NCs displayed similar static optical features, the two morphologies behaved quite differently in polarized emission. The 2D NCs exhibited detection angle dependent polarized emission, whereas the 0D NCs do not. Our findings indicate that a well-like morphology can be induced by the presence of hexadecylamine (HDA) in the dispersion with sonication for amine-passivated 0D NCs or by the use of ethanol during purification with dispersion storage for carboxylate-passivated 0D NCs. In this way, it is possible to manipulate the NC morphology for a targeted application through the appropriate post-treatment. This study highlights that more sophisticated theoretical studies are required to account for the experimental observations in which both 0D NCs and their self-assembled 2D NC products display similar static optical features

Antitumor Effect by Hydroxyapatite Nanospheres: Activation of Mitochondria-Dependent Apoptosis and Negative Regulation of Phosphatidylinositol-3-Kinase/Protein Kinase B Pathway

Hydroxyapatite nanoparticles (HA NPs) have been acknowledged for their benign biocompatibility and proliferation inhibition effect on tumor cells, attracting considerable attention for tumor therapeutics without late effects. However, unnoticeable tumor cytotoxicity of HA NPs limited the final clinical therapeutic efficacy. Herein, a two-phase synthetic approach was developed to synthesize sphere-like HA NPs by varying the conventional growth habit of HA precipitate. We present our <i>in vitro</i> and <i>in vivo</i> experimental evidence that spherical HA NPs have surprisingly high inhibitory activities against tumor cells. We demonstrate further, based on our experimental data, that the underlying cause for the death of the tumor cells is related to two concurrent pathways, the mitochondria-dependent apoptosis pathway and negative regulation of the phosphatidylinositol-3-kinase/protein kinase B (PIK3/AKT) pathway. The present study indicated that HA nanospheres can be engineered as nontoxic specific inhibitors for efficient tumor therapeutics with nanobiomaterials

Vascularization in Engineered Tissue Construct by Assembly of Cellular Patterned Micromodules and Degradable Microspheres

Tissue engineering aims to generate functional tissue constructs in which proper extracellular matrix (ECM) for cell survival and establishment of a vascular network are necessary. A modular approach via the assembly of modules mimicking the complex tissues’ microarchitectural features and establishing a vascular network represents a promising strategy for fabricating larger and more complex tissue constructs. Herein, as a model for this modular tissue engineering, engineered bone-like constructs were developed by self-assembly of osteon-like modules and fast degradable gelatin microspheres. The collagen microspheres acting as osteon-like modules were developed by seeding human umbilical vein endothelial cells (HUVECs) onto collagen microspheres laden with human osteoblast-like cells (MG63) and collagenase. Both HUVECs and MG63 cells were well spatially patterned in the modules, and collagen as ECM well supported cell adhesion, spreading, and functional expression due to its native RGD domains and enzymatic degradation activity. The patterned modules facilitated both the cellular function expression of osteogenic MG63 cells and vasculogenic HUVECs; that is, the osteon-like units were successfully achieved. The assembly of the osteon-like modules and fast degradable gelatin microspheres promoted the vascularization, thus facilitating the osteogenic function expression. The study provides a highly efficient approach to engineering complex 3D tissues with micropatterned cell types and interconnected channels

Photo-Cross-Linkable Methacrylated Gelatin and Hydroxyapatite Hybrid Hydrogel for Modularly Engineering Biomimetic Osteon

Modular tissue engineering holds great potential in regenerating natural complex tissues by engineering three-dimensional modular scaffolds with predefined geometry and biological characters. In modular tissue-like construction, a scaffold with an appropriate mechanical rigidity for assembling fabrication and high biocompatibility for cell survival is the key to the successful bioconstruction. In this work, a series of composite hydrogels (GH0, GH1, GH2, and GH3) based on a combination of methacrylated gelatin (GelMA) and hydroxyapatite (HA) was exploited to enhance hydrogel mechanical rigidity and promote cell functional expression for osteon biofabrication. These composite hydrogels presented a lower swelling ratio, higher mechanical moduli, and better biocompatibility when compared to the pure GelMA hydrogel. Furthermore, on the basis of the composite hydrogel and photolithograph technology, we successfully constructed an osteon-like concentric double-ring structure in which the inner ring encapsulating human umbilical vascular endothelial cells (HUVECs) was designed to imitate blood vessel tubule while the outer ring encapsulating human osteoblast-like cells (MG63s) acts as part of bone. During the coculture period, MG63s and HUVECs exhibited not only satisfying growth status but also the enhanced genic expression of osteogenesis-related and angiogenesis-related differentiations. These results demonstrate this GelMA–HA composite hydrogel system is promising for modular tissue engineering