Calcium Phosphate Shell Research Articles

Surface Mineralization of Engineered Bacterial Outer Membrane Vesicles to Enhance Tumor Photothermal/Immunotherapy.

Gram-negative bacteria can naturally produce nanosized spherical outer membrane vesicles (OMVs) with a lipid bilayer membrane, possessing immunostimulatory capabilities to be potentially applied in tumor therapy. However, the systemic toxicity induced by pathogen-associated molecular patterns (PAMPs) of OMVs is the main obstacle for their clinical translation. Herein, melanin-loaded OMVs were produced with a genetic engineering strategy and further coated with calcium phosphate (CaP) to reduce their toxicity to enhance tumor treatment effects. Wild-type bacterium Escherichia coli Nissle 1917 (EcN) was genetically engineered to highly express tyrosinase to catalyze the intracellular synthesis of melanin, giving melanin-loaded OMVs (OMVMel). To reduce the systemic toxicity in tumor therapy, OMVMel was coated with CaP by surface mineralization to obtain OMVMel@CaP. In comparison with OMVMel, OMVMel@CaP showed lower systemic inflammatory responses in healthy mice and less damage to the liver, spleen, lung, and kidney, so the administration dose could be increased to enhance the antitumor effect. In the acidic tumor microenvironment, the CaP shell disintegrated to release OMVMel to trigger antitumor immune responses. Under costimulation of OMVMel acting as immunoadjuvants and the damage-associated molecular patterns (DAMPs) released by the photothermal effect, the efficiency of tumor photothermal/immunotherapy was largely boosted through promoting the infiltration of matured DCs, M1 macrophages, and activated CD8+ T cells, decreasing the ratio of MDSCs in tumors.

Diffusion-driven fabrication of calcium and phosphorous-doped zinc oxide heterostructures on titanium to achieve dual functions of osteogenesis and preventing bacterial infections

Conventional Ti-based implants are vulnerable to postsurgical infection and improving the antibacterial efficiency without compromising the osteogenic ability is one of the key issues in bone implant design. Although zinc oxide (ZnO) nanorods grown on Ti substrates hydrothermally can improve the antibacterial properties, but cannot meet the stringent requirements of bone implants, as rapid degradation of ZnO and uncontrolled leaching of Zn2+ are detrimental to peri-implant cells and tissues. To solve these problems, a lattice-damage-free method is adopted to modify the ZnO nanorods with thin calcium phosphate (CaP) shells. The Ca and P ions from the CaP shells diffuse thermally into the ZnO lattice to prevent the ZnO nanorods from rapid degradation and ensure the sustained release of Zn2+ ions as well. Furthermore, the designed heterostructural nanorods not only induce the osteogenic performances of MC3T3-E1 cells but also exhibit excellent antibacterial ability against S. aureus and E. coli bacteria via physical penetration. In vivo studies also reveal that hybrid Ti-ZnO@CaP5 can not only eradicates bacteria in contact, but also provides sufficient biocompatibility without causing excessive inflammation response. Our study provides insights into the design of multifunctional biomaterials for bone implants. Statement of significance• A lattice-damage-free method is adopted to modify the ZnO nanorods with thin calcium phosphate (CaP) shells.• The dynamic process of Ca and P diffusion into the ZnO lattice is analyzed by experimental verification and theoretical calculation.• The degradation rate of ZnO nanorods is significantly decreased after CaP deposition.• The ZnO nanorods after CaP deposition can not only sterilize bacteria in contact via physical penetration, but also provide sufficient biocompatibility and osteogenic capability without causing excessive inflammation response..

Inhalable Biomineralized Liposomes for Cyclic Ca2+-Burst-Centered Endoplasmic Reticulum Stress Enhanced Lung Cancer Ferroptosis Therapy

Lung cancer with the highest mortality poses a great threat to human health. Ferroptosis therapy has recently been raised as a promising strategy for lung cancer treatment by boosting the reactive species (ROS) production and lipid peroxidation (LPO) accumulation intracellularly. However, the insufficient intracellular ROS level and the unsatisfactory drug accumulation in lung cancer lesions hamper the efficacy of ferroptosis therapy. Here, an inhalable biomineralized liposome LDM co-loaded with dihydroartemisinin (DHA) and pH-responsive calcium phosphate (CaP) was constructed as a ferroptosis nanoinducer for achieving Ca2+-burst-centered endoplasmic reticulum (ER) stress enhanced lung cancer ferroptosis therapy. Equipped with excellent nebulization properties, about 6.80-fold higher lung lesions drug accumulation than intravenous injection made the proposed inhalable LDM an ideal nanoplatform for lung cancer treatment. The Fenton-like reaction mediated by DHA with peroxide bridge structure could contribute to intracellular ROS production and induce ferroptosis. Assisted by DHA-mediated sarco-/endoplasmic reticulum calcium ATPase (SERCA) inhibition, the initial Ca2+ burst caused by CaP shell degradation triggered the Ca2+-mediated intense ER stress and subsequently induced mitochondria dysfunction to further boost ROS accumulation, which strengthens ferroptosis. The second Ca2+ burst occurred as a result of Ca2+ influx through ferroptotic pores on cell membranes, thus sequentially constructing the lethal "Ca2+ burst-ER stress-ferroptosis" cycle. Consequently, the Ca2+-burst-centered ER stress enhanced ferroptosis process was confirmed as a cell swelling and cell membrane disruption process driven by notable intracellular ROS and LPO accumulation. The proposed LDM showed an encouraging lung retention property and extraordinary antitumor ability in an orthotropic lung tumor murine model. In conclusion, the constructed ferroptosis nanoinducer could be a potential tailored nanoplatform for nebulization-based pulmonary delivery and underscore the application of Ca2+-burst-centered ER stress enhanced lung cancer ferroptosis therapy.

Surface modification of titanium substrate via combining photothermal therapy and quorum-sensing-inhibition strategy for improving osseointegration and treating biofilm-associated bacterial infection.

Insufficient osseointegration and biofilm-associated bacterial infection are important challenges for clinical application of titanium (Ti)-based implants. Here, we constructed mesoporous polydopamine (MPDA) nanoparticles (NPs) loaded with luteolin (LUT, a quorum sensing inhibitor), which were further coated with the shell of calcium phosphate (CaP) to construct MPDA-LUT@CaP nanosystem. Then, MPDA-LUT@CaP NPs were immobilized on the surface of Ti implants. Under acidic environment of bacterial biofilm-infection, the CaP shell of MPDA-LUT@CaP NPs was rapidly degraded and released LUT, Ca2+ and PO43− from the surface of Ti implant. LUT could effectively inhibit and disperse biofilm. Furthermore, under near-infrared irradiation (NIR), the thermotherapy induced by the photothermal conversion effect of MPDA destroyed the integrity of the bacterial membrane, and synergistically led to protein leakage and a decrease in ATP levels. Combined with photothermal therapy (PTT) and quorum-sensing-inhibition strategy, the surface-functionalized Ti substrate had an antibacterial rate of over 95.59% against Staphylococcus aureus and the elimination rate of the formed biofilm was as high as 90.3%, so as to achieve low temperature and efficient treatment of bacterial biofilm infection. More importantly, the modified Ti implant accelerated the growth of cell and the healing process of bone tissue due to the released Ca2+ and PO43−. In summary, this work combined PTT with quorum-sensing-inhibition strategy provides a new idea for surface functionalization of implant for achieving effective antibacterial and osseointegration capabilities.

Shielding Ferritin with a Biomineralized Shell Enables Efficient Modulation of Tumor Microenvironment and Targeted Delivery of Diverse Therapeutic Agents

Ferritin (Fn) is considered a promising carrier for targeted delivery to tumors, but the successful application in vivo has not been fully achieved yet. Herein, strong evidence is provided that the Fn receptor is expressed in liver tissues, resulting in an intercept effect in regards to tumor delivery. Building on these observations, a biomineralization technology is rationally designed to shield Fn using a calcium phosphate (CaP) shell, which can improve the delivery performance by reducing Fn interception in the liver while re-exposing it in acidic tumors. Moreover, the selective dissolution of the CaP shell not only neutralizes the acidic microenvironment but also induces the intratumoral immunomodulation and calcification. Upon multiple cell line and patient-derived xenografts, it is demonstrated that the elaboration of the highly flexible Fn@CaP chassis by loading a chemotherapeutic drug into the Fn cavity confers potent antitumor effects, and additionally encapsulating a photosensitizer into the outer shell enables a combined chemo-photothermal therapy for complete suppression of advanced tumors. Altogether, these results support Fn@CaP as a new nanoplatform for efficient modulation of the tumor microenvironment and targeted delivery of diverse therapeutic agents.

Deposition of non-porous calcium phosphate shells onto liquid filled microcapsules

The efficient encapsulation of small molecule active ingredients has been a challenge for many decades across many commercial applications. Recently, successful attempts to address this issue have included deposition of thin metal shells onto liquid filled polymer microcapsules or emulsion droplets to provide an impermeable barrier to diffusion. In this work we have developed a novel method to protect small molecule active ingredients by deposition of thin mineral shells. Platinum nanoparticles are used to catalyse and direct growth of a calcium phosphate shell onto liquid filled polymer microcapsules under various reaction conditions. Findings indicate that a non-porous protective shell is formed on the majority of the microcapsule population, with small concentrations of the core material being released only from those microcapsules with defects, over a 7 days period, when conducting forced release studies into a solvent for the core oil. The resulting microcapsules show no significant cell toxicity when exposed to HEK 293 cells for 72 h.

Cascade-responsive nanobomb with domino effect for anti-tumor synergistic therapies.

The development of reactive oxygen species (ROS) generation agents that can selectively produce sufficient ROS at the tumor site without external energy stimulation is of great significance for the further clinical application of ROS-based therapies. Herein, we designed a cascade-responsive ROS nanobomb (ZnO2@Ce6/CaP@CPPO/BSA, designated as Z@Ce6/CaP@CB) with domino effect and without external stimulation for the specific generation of multiple powerful ROS storms at the tumor site. The calcium phosphate shell and ZnO2 core gradually degrade and release Ca2+, Zn2+ and hydrogen peroxide (H2O2) under acid stimulation. On the one hand, Zn2+ can enhance the generation of endogenous superoxide anions (·O2–) and H2O2 through the inhibition of the mitochondrial electron transport chain. On the other hand, the generation of large amounts of exogenous H2O2 can cause oxidative damage to tumor cells and further activate bis[2,4,5-trichloro-6-(pentyloxycarbonyl)phenyl] oxalate (CPPO)-mediated chemiexcited photodynamic therapy. In addition, the oxidative stress caused by the generated ROS can lead to the uncontrolled accumulation of Ca2+ in cells and further result in Ca2+ overload-induced cell death. Therefore, the introduction of Z@Ce6/CaP@CB nanobombs triggered the ‘domino effect’ that caused multiple heavy ROS storms and Ca2+ overload in tumors and effectively activated anti-tumor immune response.

Biomineralized Bacterial Outer Membrane Vesicles Potentiate Safe and Efficient Tumor Microenvironment Reprogramming for Anticancer Therapy.

The highly immunosuppressive tumor microenvironment (TME) in solid tumors often dampens the efficacy of immunotherapy. In this study, bacterial outer membrane vesicles (OMVs) are demonstrated as powerful immunostimulants for TME reprogramming. To overcome the obstacles of antibody-dependent clearance and high toxicity induced by OMVs upon intravenous injection (a classic clinically relevant delivery mode), calcium phosphate (CaP) shells are employed to cover the surface of OMVs, which enables potent OMV-based TME reprograming without side effects. Meanwhile, the pH-sensitive CaP shells facilitate the neutralization of acidic TME, leading to highly beneficial M2-to-M1 polarization of macrophages for improved antitumor effect. Moreover, the outer shells can be integrated with functional components like folic acid or photosensitizer agents, which facilitates the use of the OMV-based platform in combination therapies for a synergic therapeutic effect.

Incorporation of drug efflux inhibitor and chemotherapeutic agent into an inorganic/organic platform for the effective treatment of multidrug resistant breast cancer

BackgroundMultidrug resistance (MDR) is a pressing obstacle in clinical chemotherapy for breast cancer. Based on the fact that the drug efflux is an important factor in MDR, we designed a codelivery system to guide the drug efflux inhibitor verapamil (VRP) and the chemotherapeutic agent novantrone (NVT) synergistically into breast cancer cells to reverse MDR.ResultsThis co-delivery system consists of following components: the active targeting peptide RGD, an inorganic calcium phosphate (CaP) shell and an organic inner core. VRP and NVT were loaded into CaP shell and phosphatidylserine polyethylene glycol (PS-PEG) core of nanoparticles (NPs) separately to obtain NVT- and VRP-loaded NPs (NV@CaP-RGD). These codelivered NPs allowed VRP to prevent the efflux of NVT from breast cancer cells by competitively combining with drug efflux pumps. Additionally, NV@CaP-RGD was effectively internalized into breast cancer cells by precise delivery through the effects of the active targeting peptides RGD and EPR. The pH-triggered profile of CaP was also able to assist the NPs to successfully escape from lysosomes, leading to a greatly increased effective intracellular drug concentration.ConclusionThe concurrent administration of VRP and NVT by organic/inorganic NPs is a promising therapeutic approach to reverse MDR in breast cancer.

Enhancement of near-infrared emission of neodymium-doped monoclinic gadolinium phosphate nanophosphors by surface coating with calcium phosphate

ABSTRACTCore/shell-type nanoparticles composed of GdPO4: x mol% Nd3+/calcium phosphate (CaPO) (0 ≤ x ≤ 5) were synthesized by a precipitation method, as nontoxic bio imaging phosphors that can emit near-infrared (NIR) light under NIR excitation. The GdPO4: x mol% Nd3+ core, obtained in a single-phase form of the monoclinic rare-earth orthophosphate structure, exhibited characteristic emissions attributed to the f–f transitions of Nd3+. The strongest emission peak was observed at 1061 nm under excitation at 800 nm in a sample containing 3 mol% of Nd3+. The average particle size of GdPO4: 3 mol% Nd3+ was 42 nm, indicating that nano-sized particles were successfully obtained. Although the average particle size of the core/shell-type GdPO4: 3 mol% Nd3+/CaPO nanophosphor was slightly increased to 54 nm by a second calcination in the surface coating process, the CaPO shell was well formed with a thickness of 3 nm around the GdPO4: 3 mol% Nd3+ core. With surface coating with the CaPO4 shell, the NIR emission intensity increased to 4.2 times higher than that of GdPO4: 3 mol% Nd3+. This emission intensity was significantly higher than that of indocyanine green, moreover, which is used in practice as an organic bioimaging reagent.

Synthesis of Silica-Coated Magnetic Hydroxyapatite Composites for Drug Delivery Applications.

We have prepared a core-shell magnetic silica-coated hydroxyapatite, Fe₃O₄@SiO₂@HAp composite materials for pH-responsive drug delivery applications. Captopril (Cap) and ibuprofen (Ibu) were chosen as model hydrophilic and hydrophobic drugs, respectively. The drugs were encapsulated into the Fe₃O₄@SiO₂@HAp composite via electrostatic interactions with existing amine and carboxylic acid groups during calcium phosphate shell formation. The formation of calcium phosphate shell not only protects the encapsulated drugs from leaching but also controls the release rate of drugs from the composite system depending on various pH conditions. We have tested the release behavior of Cap and Ibu drugs under different pH conditions such as neutral pH (pH 7.4) and acidic pH (pH 5.0), respectively. The study result reveals that the synthesized Fe₃O₄@SiO₂@HAp composite is suitable for release of both water soluble and water insoluble drugs based on a pH-responsive controlled manner.

Coextrusion-Based 3D Plotting of Ceramic Pastes for Porous Calcium Phosphate Scaffolds Comprised of Hollow Filaments.

This paper demonstrates the utility of coextrusion-based 3D plotting of ceramic pastes (CoEx-3DP) as a new type of additive manufacturing (AM) technique, which can produce porous calcium phosphate (CaP) ceramic scaffolds comprised of hollow CaP filaments. In this technique, green filaments with a controlled core/shell structure can be produced by coextruding an initial feedrod, comprised of the carbon black (CB) core and CaP shell, through a fine nozzle in an acetone bath and then deposited in a controlled manner according to predetermined paths. In addition, channels in CaP filaments can be created through the removal of the CB cores during heat-treatment. Produced CaP scaffolds had two different types of pores with well-defined geometries: three-dimensionally interconnected pores (~360 × 230 μm2 in sizes) and channels (>100 μm in diameter) in hollow CaP filaments. The porous scaffolds showed high compressive strengths of ~12.3 ± 2.2 MPa at a high porosity of ~73 vol % when compressed parallel to the direction of the hollow CaP filaments. In addition, the mechanical properties of porous CaP scaffolds could be tailored by adjusting their porosity, for example, compressive strengths of 4.8 ± 1.1 MPa at a porosity of ~82 vol %. The porous CaP scaffold showed good biocompatibility, which was assessed by in vitro cell tests, where several the cells adhered to and spread actively with the outer and inner surfaces of the hollow CaP filaments.

Inorganic Self-Assembled Bioactive Artificial Proto-Osteocells Inducing Bone Regeneration.

Since the discovery of osteoinduction in the early 20th century, innovative biomaterials with osteoinductive potential have emerged as candidates for bone repair. Recently, artificial protocell models have demonstrated great potential for tissue regeneration. Herein, we developed artificial bioactive proto-osteocells by self-assembly of biodegradable biphasic-phosphate particles in the form of aqueous bone morphogenetic protein 2 (BMP2)-containing Pickering emulsions in corn oil to fulfill the release of BMP2 with controlled and local efficacy. These artificial proto-osteocells have the advantage of (1) being directly injected into the target location to avert reported side effects of BMP2, minimizing surgical complications, (2) exhibiting the capability of osteoinduction as shown in both in vitro and in vivo models, and (3) demonstrating calcific deposition locally by utilizing the biodegradable calcium phosphate shell. The efficiency of BMP2 within the artificial proto-osteocells showed 25 times greater bone-inducing potential when compared to the control. This study demonstrates for the first time a new strategy toward utilizing material-based artificial proto-osteocells to tackle medical issues in bone tissue repair and regeneration.

Multifunctional Shell–Core Nanoparticles for Treatment of Multidrug Resistance Hepatocellular Carcinoma

AbstractMultidrug resistance (MDR) is the main obstruction against the chemotherapy for hepatocellular carcinoma. Herein, a biodegradable multifunctional tumor‐targeted core–shell structural nanocarrier (RGD peptide functionalized nanoparticles, RGD‐NPs) is reported for treating MDR hepatocellular carcinoma, which consists of three components: pH‐triggered calcium phosphate shell, long circulation phosphatidylserine‐polyethylene glycol (PS‐PEG) core, and an active targeting ligand RGD peptide. Drug‐resistance inhibitor (verapamil, VER) and chemotherapeutic agent (mitoxantrone, MIT) are separately encapsulated into the outer shell layer and inner core layer to obtain VER and MIT loaded RGD‐NPs (VM‐RGD‐NPs). Due to the shell–core structure, the VER and MIT can release sequentially, thus synergistically weakening the efflux effect to MIT by MDR cells. Also, the calcium phosphate can trigger lysosomal escaping through the varied pH value. Together with the optimized internalization pathway in MDR tumor cells, the increased intracellular effective chemotherapeutic drug concentration can be realized, thus achieving the improved curative effect. In this system, the PEG extends the circulation time in vivo. Also, the peptide RGD distinctly increases the affinity to MDR tumors with respect to nontargeted nanoparticles. As a consequence, VM‐RGD‐NPs exhibit a significant synergistic effect toward the MDR hepatocellular carcinoma, providing a promising therapeutic approach for MDR tumor.

Streptococcus pneumoniae Attenuated Strain SPY1 with an Artificial Mineral Shell Induces Humoral and Th17 Cellular Immunity and Protects Mice against Pneumococcal Infection.

Streptococcus pneumoniae is a major pathogen leading to substantial morbidity and mortality in children under 5 years of age. Vaccination is an effective strategy to prevent S. pneumoniae infection. SPY1 is a pneumococcal vaccine candidate strain obtained in our previous study. To improve its stability and immunogencity, in this study, we constructed the SPY1ΔlytA strain that lacks autolysin activity and was coated with an artificial exterior surface calcium phosphate shell by in situ mineralization. The resulting strain SPY1ΔlytACaPi displayed enhanced thermal stability enabling storage at 37°C for 1 week. Furthermore, mucosal and subcutaneous immunization with the SPY1ΔlytACaPi strain induced better protective effects than SPY1ΔlytA in anti-colonization after challenging with 19F and anti-invasion by D39 in mice. Subcutaneous immunization with SPY1ΔlytACaPi elicited higher IgG level while mucosal immunization primarily elicited an immune response which is supposed to be related to Th17 cells. Taken together, the mineralized strain may be a promising candidate for an attenuated S. pneumoniae vaccine.

GEOBIOLOGICAL AND DIAGENETIC INSIGHTS FROM MALVINOKAFFRIC DEVONIAN BIOTA (CHAPADA GROUP, PARANÁ BASIN, BRAZIL): PALEOBIOLOGICAL AND PALEOENVIRONMENTAL IMPLICATIONS

This study tests the presence of differential preservation in the Devonian Malvinokaffric fauna from the Chapada Group (Parana Basin, Brazil). Results of EDXRF, EDS, Raman Spectroscopy, and petrographic analyses show differential preservation of shells that were originally calcite as hematite and goethite fossils, while organisms with original calcium phosphate shells tend to be preserved inside phosphatic concretions. Both preservation types are commonly associated with pseudoframboids, while calcium sulfate minerals are commonly associated with hematized fossils. From this evidence, a diagenetic model for these fossils is proposed. The model includes an early diagenetic phase (characterized by anaerobic sulfate reduction and precipitation of pyrite and carbonate-fluorapatite) and a second, near-surface chemical weathering phase (characterized by the oxidation of pyrite and precipitation of iron oxyhydroxides and calcium sulfates). Acidic conditions in both phases may account for the dissolution of less stable minerals compared to calcium phosphate. It is considered that this model may assist in understanding other similarly preserved biotas, as well as enhancing understanding of the taphonomic overprint that may occur within this important and endemic Devonian biota.

The Lingula genome provides insights into brachiopod evolution and the origin of phosphate biomineralization.

The evolutionary origins of lingulid brachiopods and their calcium phosphate shells have been obscure. Here we decode the 425-Mb genome of Lingula anatina to gain insights into brachiopod evolution. Comprehensive phylogenomic analyses place Lingula close to molluscs, but distant from annelids. The Lingula gene number has increased to ∼34,000 by extensive expansion of gene families. Although Lingula and vertebrates have superficially similar hard tissue components, our genomic, transcriptomic and proteomic analyses show that Lingula lacks genes involved in bone formation, indicating an independent origin of their phosphate biominerals. Several genes involved in Lingula shell formation are shared by molluscs. However, Lingula has independently undergone domain combinations to produce shell matrix collagens with EGF domains and carries lineage-specific shell matrix proteins. Gene family expansion, domain shuffling and co-option of genes appear to be the genomic background of Lingula's unique biomineralization. This Lingula genome provides resources for further studies of lophotrochozoan evolution.

Preparation of inorganic/organic polymer hybrid microcapsules with high encapsulation efficiency by an electrospray technique.

Microcapsules composed of calcium phosphate and chitosan were prepared in a single step by electrospraying. An aqueous solution containing calcium chloride and chitosan was electrosprayed into a phosphate solution to form a calcium phosphate shell on the sprayed droplets. The resulting microcapsules were 350 μm in average diameter. Investigation using fluorescently labeled chitosan and XRD measurements revealed that the shells of the microcapsules were composed of calcium phosphate (mainly hydroxyapatite) and chitosan. Instead of chitosan, poly(diallyldimethylammonium chloride) and polyethylene glycol were also available for microcapsule production by electrospraying. Variations in the electrospraying conditions resulted in a variety of microcapsule shapes. Various types of substrates were successfully encapsulated in microcapsules with a high encapsulation efficiency (more than 80%). Finally, we succeeded in the encapsulation of living yeast cells in microcapsules, and observed their growth within these microcapsules.

Preparation and properties of biocompatible PS-PEG/calcium phosphate nanospheres

A facile room-temperature method was used to prepare phosphatidylserine (PS)-poly(ethylene glycol) (PEG)/calcium phosphate (CaP) nanospheres (PS-poly(ethylene glycol) methyl ether/CaP nanospheres). Transmission electron microscopy (TEM) results confirmed that the PS-PEG/CaP porous nanospheres were spherical with a diameter of 8–12 nm. X-ray and thermo-gravimetric analysis (TGA) results also confirmed that the PS-PEG micelle was packed in the CaP shell. PS-PEG/CaP nanospheres exhibited little effect on the hemolysis, coagulation characteristics of blood and inflammatory response, demonstrating a negligible cytotoxicity response in LO2 liver cells. Experiments performed in zebrafish demonstrated that the PS-PEG/CaP nanospheres had a long circulatory residence time and did not induce apoptosis in zebrafish. Taken together, these results suggest that the PS-PEG/CaP nanospheres have great potential to be used as a drug carrier.

Inorganic–Organic Hybrid Nanoparticles with Biocompatible Calcium Phosphate Thin Shells for Fluorescence Enhancement

Polymeric micelles consisting of asymmetric triblock copolymers were successfully used for fabrication of robust hybrid nanoparticles with highly biocompatible calcium phosphate shells. The hydrophobic polystyrene core encapsulates hydrophobic fluorescent dyes such as Nile red. The anionic polyacrylic acid provides the site for the mineralization reaction of calcium phosphate. The polyethylene glycol corona stabilizes the hybrid nanoparticles. Fluorescent dyes can be used as imaging agents for determining the location of the nanoparticles and to give an observable indication of drug delivery, while the calcium phosphate shell can enhance the fluorescence of the encapsulated dye.