Facile one-pot fabrication of calcium phosphate-based composite nanoparticles as delivery and MRI contrast agents for macrophages

Nakamura, Minoru; Oyane, Ayako; Kuroiwa, Kiyoko; Shimizu, Yoshiki; Pyatenko, Alexander; Misawa, Masaki; Numano, Tomokazu; Kosuge, Hisanori

doi:10.1016/j.colsurfb.2017.11.034

Cited by 18 publications

(25 citation statements)

References 39 publications

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“…Another reason might be that IBN itself exerted a particledownsizing effect, i.e., an inhibitory effect on CaP particle growth. 56 A effect of IBN is consistent with the observation that the primary particle size of CaP-IBN (less than 50 nm, Figure 2m) was smaller than that of CaP (approximately 100−150 nm, Figure 2n). 4.2.1.…”

Section: Cell Viability Of Osteoclastssupporting

confidence: 88%

Ibandronate-Loaded Carbon Nanohorns Fabricated Using Calcium Phosphates as Mediators and Their Effects on Macrophages and Osteoclasts

Nakamura

Ueda

Yamamoto

et al. 2021

ACS Appl. Mater. Interfaces

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Carbon nanohorns (CNHs), a type of nanocarbon, have been studied for the application of drug delivery systems (DDSs) because they are easily functionalized, support bone regeneration, can be used to perform photohyperthermia, have low toxicity, and are easily phagocytosed by macrophages. To take advantage of these features of CNHs, we developed a DDS for the local treatment of bone metastasis by loading the antibone resorption drug ibandronate (IBN) onto CNHs. The poor adsorption of IBN onto CNHs due to the weak hydrophilic− hydrophobic interaction was overcome by using calcium phosphates (CaPs) as mediators. In the fabrication process, we used oxidized CNH (OxCNH), which is less hydrophobic, onto which IBN was coprecipitated with CaP from a labile supersaturated CaP solution. OxCNH−CaP−IBN composite nanoparticles exerted stronger cell-suppressive effects than OxCNH and IBN in both murine macrophages (RAW264.7 cells) and osteoclasts (differentiated from RAW264.7 cells). OxCNH−CaP−IBN composite nanoparticles were efficiently phagocytosed by macrophage cells, where they specifically accumulated in lysosomes. The stronger cell-suppressive effects were likely due to intracellular delivery of IBN, i.e., the release of IBN from OxCNH−CaP−IBN composite nanoparticles via dissociation of CaP in the acidic environment of lysosomes. Our findings suggest that OxCNH−CaP−IBN composite nanoparticles are potentially useful for the local treatment of metastatic bone destruction.

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Section: Cell Viability Of Osteoclastssupporting

confidence: 88%

Ibandronate-Loaded Carbon Nanohorns Fabricated Using Calcium Phosphates as Mediators and Their Effects on Macrophages and Osteoclasts

Nakamura

Ueda

Yamamoto

et al. 2021

ACS Appl. Mater. Interfaces

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“…In recent years, certain types of biomolecules have been applied as dispersants in place of synthetic surfactants in the precipitation process of CaP-based nanoparticles [ 8 ]. For example, nucleic acids [ 9 , 10 ], proteins [ 11 , 12 ], and polysaccharides [ 13 , 14 , 15 , 16 , 17 ] have been immobilized on or within CaP nanoparticles, thereby allowing their dispersion even in the absence of synthetic surfactants. Among these biomolecules, heparin is of particular interest, since it is the oldest and most commonly used antithrombotic drug and has a high affinity with CaPs.…”

Section: Introductionmentioning

confidence: 99%

High Immobilization Efficiency of Basic Protein within Heparin-Immobilized Calcium Phosphate Nanoparticles

Nakamura

Bunryo²,

Narazaki³

et al. 2022

IJMS

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Previously, we achieved one-pot fabrication of heparin-immobilized calcium phosphate (CaP) nanoparticles with high dispersibility by a precipitation process in a highly supersaturated reaction solution. In this study, we revealed that the heparin-immobilized CaP nanoparticles have a greater co-immobilizing capacity for basic proteins than for acidic proteins. In this process, heparin acted as not only a particle-dispersing agent but also as an immobilizing agent for basic proteins; it remarkably (approximately three-fold) improved the immobilization efficiency of cytochrome C (a model basic protein) within the CaP nanoparticles. The content of cytochrome C immobilized within the nanoparticles was increased with an increase in cytochrome C concentration in the reaction solution and by aging the nanoparticles. The obtained nanoparticles were dispersed well in water owing to their large negative zeta potentials derived from heparin, irrespective of the content of cytochrome C. Similar results were obtained also for another basic protein, lysozyme, but not for an acidic protein, albumin; the immobilization efficiency of albumin within the nanoparticles was decreased by heparin. These findings provide new insights into the co-immobilization strategy of proteins within heparin-immobilized CaP nanoparticles and will be useful in the design and fabrication of nanocarriers for protein delivery applications.

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“…An effective nanovaccine is often composed of an antigen, immune stimulant adjuvant, and nanomaterial as the delivery vehicle. , Calcium phosphate (CP) is a mineral material found in native bones and teeth, which exhibits good biocompatibility, high affinity for various biomolecules, and degradability under acidic conditions. Meanwhile, CP can be easily synthesized from common and inexpensive inorganic sources, which are easy for large-scale production . These characteristics make CP a good candidate for drug and gene delivery. , Furthermore, CP has the vaccine adjuvant ability by activating the maturation of APCs (immunostimulation), which is used in several commercial vaccines , and tested in human .…”

Section: Introductionmentioning

confidence: 99%

“…Meanwhile, CP can be easily synthesized from common and inexpensive inorganic sources, which are easy for large-scale production. 14 These characteristics make CP a good candidate for drug and gene delivery. 15,16 Furthermore, CP has the vaccine adjuvant ability 17 by activating the maturation of APCs (immunostimulation), which is used in several commercial vaccines 18,19 and tested in human.…”

Section: ■ Introductionmentioning

confidence: 99%

Mannose-Functionalized Biodegradable Nanoparticles Efficiently Deliver DNA Vaccine and Promote Anti-tumor Immunity

Sun

Zhao

et al. 2021

ACS Appl. Mater. Interfaces

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Cancer vaccines have attracted increasing attention for their application in tumor immunotherapy. DNA vaccines are one of them that have been proven very promising with the advantages of safety, rapid design, and low cost. However, the low stability, ineffective cell internalization, and low immunostimulation hinder their wide application. Thus, developing targeted and safe systems to effectively deliver DNA vaccines becomes a vital step. In this study, we report the development of mannose-and bisphosphonate (BP)modified calcium phosphate (CP) nanoparticles (NPs) as efficient vaccine delivery vehicles by targeting C-type lectin receptors (CLRs) on antigen-presenting cells (APCs). Using a model antigen ovalbumin (OVA)-encoded plasmid DNA (pOVA) as a model vaccine, we demonstrate that mannose-modified and BP-stabilized CP (MBCP) nanoparticles are monodispersed for enhanced uptake by APCs and subsequently induce OVA antigen presentation and immunostimulation. Mice immunized with MBCP-pOVA nanovaccines show a significantly stronger anti-OVA antibody response with a quicker IgG1 and IgG2a antibody production than unmodified NPs. Moreover, MBCP-pOVA immunization significantly inhibits the growth of OVA-expressing E.G7 tumor cells in C57BL/6J mice. Our data collectively suggest that the modifications to enhance the stability and targeting ability of MBCP NPs are essential for effective delivery of DNA vaccines and promote robust anti-tumor immunity.

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Facile one-pot fabrication of calcium phosphate-based composite nanoparticles as delivery and MRI contrast agents for macrophages

Cited by 18 publications

References 39 publications

Ibandronate-Loaded Carbon Nanohorns Fabricated Using Calcium Phosphates as Mediators and Their Effects on Macrophages and Osteoclasts

Ibandronate-Loaded Carbon Nanohorns Fabricated Using Calcium Phosphates as Mediators and Their Effects on Macrophages and Osteoclasts

High Immobilization Efficiency of Basic Protein within Heparin-Immobilized Calcium Phosphate Nanoparticles

Mannose-Functionalized Biodegradable Nanoparticles Efficiently Deliver DNA Vaccine and Promote Anti-tumor Immunity

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