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In recent years, porous titanium (Ti) scaffolds with BaTiO3 coatings have been designed to promote bone regeneration. However, the phase transitions of BaTiO3 have been understudied, and their coatings have yielded low effective piezoelectric coefficients (EPCs < 1 pm/V). In addition, piezoelectric nanomaterials bring many advantages in eliciting cell-specific responses. However, no study has attempted to design a nanostructured BaTiO3 coating with high EPCs. Herein, nanoparticulate tetragonal phase BaTiO3 coatings with cube-like nanoparticles but different effective piezoelectric coefficients were fabricated via anodization combining two hydrothermal processes. The effects of nanostructure-mediated piezoelectricity on the spreading, proliferation, and osteogenic differentiation of human jaw bone marrow mesenchymal stem cells (hJBMSCs) were explored. We found that the nanostructured tetragonal BaTiO3 coatings exhibited good biocompatibility and an EPC-dependent inhibitory effect on hJBMSC proliferation. The nanostructured tetragonal BaTiO3 coatings of relatively smaller EPCs (<10 pm/V) exhibited hJBMSC elongation and reorientation, broad lamellipodia extension, strong intercellular connection and osteogenic differentiation enhancement. Overall, the improved hJBMSC characteristics make the nanostructured tetragonal BaTiO3 coatings promising for application on implant surfaces to promote osseointegration. [ABSTRACT FROM AUTHOR]

Novel strategies for diagnosing triple-negative breast cancer (TNBC) are essential for effective clinical treatment. Vascular endothelial growth factor receptor 2 (VEGFR2) and neuropilin-1 (NRP-1) are potential targets for tumor imaging agents. We designed and synthesized [99mTc]Tc-labeled heptapeptide (A7R) and its D-type peptide (DA7R) with high affinity and specificity for VEGFR2 and NRP-1 as novel single-photon emission computed tomography (SPECT) probes for TNBC imaging. The specificities of A7R and DA7R were first evaluated in vitro using flow cytometry and confocal microscopy and ex vivo using fluorescence imaging. Subsequently, A7R and DA7R were labeled with [99mTc]Tc through 6-hydrazino nicotinamide (HYNIC), and their radiochemical purities (RCPs) and stability in vitro were assessed. The imaging performance and biodistribution of [99mTc]Tc-HYNIC-A7R and [99mTc]Tc-HYNIC-DA7R were evaluated in TNBC mouse models. A7R and DA7R exhibited good TNBC cell-targeting abilities and were readily labeled with [99mTc]Tc through HYNIC. Both [99mTc]Tc-HYNIC-A7R and [99mTc]Tc-HYNIC-DA7R had high RCPs and stability in vitro, and their accumulation in tumor tissues in the TNBC models was evident, with fast blood clearance and favorable biodistribution. More importantly, [99mTc]Tc-HYNIC-DA7R showed better tumor-to-muscle ratios and lower renal uptake than [99mTc]Tc-HYNIC-A7R. These results suggest that both [99mTc]Tc-HYNIC-DA7R and [99mTc]Tc-HYNIC-A7R have substantial potential as probes for targeted SPECT imaging of TNBC, and the former may be considered for future clinical translation owing to its superior tumor imaging performance. [ABSTRACT FROM AUTHOR]

The design and fabrication of nanoplatforms with both nuclear medical imaging and therapeutic functions remain challenging in current precision nanomedicine. Herein, we report the design of a novel nanoplatform based on glucose-modified dendrimer-entrapped gold nanoparticles (Au DENPs) labeled with radionuclide 68Ga and incorporated with cytosine-guanine (CpG) oligonucleotide for positron emission tomography (PET)/computed tomography (CT) dual-mode imaging and immunotherapy of tumors. In this study, generation 5 poly(amidoamine) (PAMAM) dendrimers were first modified to have 8.2 DOTA and 7.3 polyethylene glycol with the other end functionalized with 2-amino-2-deoxy- D -glucose (DG) for each dendrimer, entrapped with Au NPs, and then radiolabeled with 68Ga through the DOTA chelation. The synthesized DG-Au DENPs have good cytocompatibility, targeting specificity toward cancer cells expressing glucose transporters, and the ability to be labeled by 68Ga with great labeling efficiency (≥85%) and stability (≥95%). After being loaded with CpG, the formed DG-Au DENPs/CpG polyplexes were proven to be used for tumor dual-mode PET/CT imaging and immunotherapy by effectively maturing dendritic cells to initiate a T cell-based antitumor immune response in vivo. Compared with the DG-free polyplexes, the developed DG-Au DENPs/CpG polyplexes show a much more sensitive imaging effect and better inhibition effect of tumors. These findings demonstrate a unique design of 68Ga-labeled DG-Au DENPs, a promising theranostic nanoplatform that may be extended to tackle different tumor types. [ABSTRACT FROM AUTHOR]

Certain receptors are often overexpressed during tumor occurrence and development and closely correlate with carcinogenesis. Owing to its overexpression on the cell membrane and cytoplasm of various tumors, plectin, which is involved in tumor proliferation, migration, and invasion, has been viewed as a promising target for cancer imaging. Hence, plectin-targeting agents have great potential as imaging probes for tumor diagnosis. In this study, we developed a [99mTc]Tc-labeled plectin-targeted peptide (PTP) as a novel single-photon emission computed tomography (SPECT) probe for tumor imaging and investigated its pharmacokinetics, biodistribution, and targeting ability in several types of tumor-bearing mouse models. The PTP had good biocompatibility and targeting ability to tumor cells in vitro and could be readily labeled with [99mTc]Tc after modification with the bifunctional chelator 6-hydrazino nicotinamide (HYNIC). Furthermore, the prepared [99mTc]Tc-labeled PTP ([99mTc]Tc-HYNIC-PTP) showed high radiochemical purity and excellent stability in vitro. In addition, favorable biodistribution, fast blood clearance, and clear accumulation of [99mTc]Tc-HYNIC-PTP in several types of tumors were observed, with a good correlation between tumor uptake and plectin expression levels. These results indicate the potential of [99mTc]Tc-HYNIC-PTP as a novel SPECT probe for tumor imaging. [ABSTRACT FROM AUTHOR]

This study was to investigate the synthesis and biological evaluation of [99mTc]Tc-labeled Buthus martensii Karsch Chlorotoxin ([99mTc]Tc-BmK CT) as a radiopharmaceutical for glioma single photon computed emission tomography (SPECT) imaging. The results showed that BmK CT peptide modified with a hexahistidine tag displayed good cytocompatibility in vitro, and could be efficiently radiolabeled with 99mTc via [99mTc]Tc-tricarbonyl chemistry. The [99mTc]Tc-BmK CT showed satisfactory radiochemical purity and stability in vitro, and could be developed as a probe for targeted SPECT imaging of glioma cells in vitro and in a tumor-bearing mouse model. Our data indicated that the synthesized [99mTc]Tc-BmK CT might be developed as a promising imaging agent for glioma diagnostic application. [ABSTRACT FROM AUTHOR]