Biomimetic nanoparticles (NPs) have been actively studied for their biological compatibility due to its distinguished abilities viz. long-term circulation, low toxicity, ease for surface modification, and its ability to avoid phagocytosis of NPs by macrophages. Coating the NPs with a variety of cell membranes bearing the immune control proteins increases drug efficacy while complementing the intrinsic advantages of the NPs. In this study, efforts were made to introduce oxophilic radiometal 89Zr with hollow mesoporous silica nanospheres (HMSNs) having abundant silanol groups and were bioengineered with red blood cell membrane (Rm) having cluster of differentiation 47 (CD47) protein to evaluate its long-term in vivo behavior. We were successful in demonstrating the increased in vivo stability of synthesized Rm-camouflaged, 89Zr-labelled HMSNs with the markedly reduced 89Zr release. Rm camouflaged 89Zr-HMSNs effectively accumulated in the tumor by avoiding phagocytosis of macrophages. In addition, re-injecting the Rm isolated using the blood of the same animal helped to overcome the immune barrier. This novel strategy can be applied extensively to identify the long-term in vivo behavior of nano-drugs while enhancing their biocompatibility.
In this study, we investigated the tumor targeting effect in cancer cells using triphenylphosphonium (TPP) cations, which are accumulated by differences in membrane potential, and folic acid (FA), which is selectively bound to overexpressed receptors on various cancer cells. We used Food and Drug Administration (FDA)-approved silica nanoparticles (SNPs) as drug carriers, and SNPs conjugated with TPP and FA (STFs) samples were prepared by introducing different amounts of TPP and FA onto the nanoparticle surfaces. STF-1, 2, 3, 4 and 5 are named according to the combination ratio of TPP and FA on the particle surface. To confirm the tumor targeting effect, 89Zr (t1/2 = 3.3 days) was coordinated directly to the silanol group of SNP surfaces without chelators. It was shown that the radiochemical yield was 69% and radiochemical purity was >99%. In the cellular uptake evaluation, SNPs with the most TPP (SFT-5) and FA (SFT-1) attached indicated similar uptake tendencies for mouse colon cancer cells (CT-26). However, the results of the cell internalization assay and measurement of positron emission tomography (PET) images showed that SFT-5 had more affinity for the CT-26 tumor than other samples the TPP ratio of which was lower. Consequently, we confirmed that TPP ligands affect target cancer cells more than FA, which means that cell membrane potential is significantly effective for tumor targeting.
We report column material for a 68Ge/68Ga generator with acid resistance and excellent adsorption and desorption capacity of 68Ge and 68Ga, respectively. Despite being a core element of the 68Ge/68Ga generator system, research on this has been insufficient. Therefore, we synthesized a low molecular chitosan-based TiO2 (LC-TiO2) adsorbent via a physical trapping method as a durable 68Ge/68Ga generator column material. The adsorption/desorption studies exhibited a higher separation factor of 68Ge/68Ga in the concentration range of HCl examined (0.01 M to 1.0 M). The prepared LC-TiO2 adsorbent showed acid resistance capabilities with >93% of 68Ga elution yield and 1.6 × 10−4% of 68Ge breakthrough. In particular, the labeling efficiency of DOTA and NOTA, by using the generator eluted 68Ga, was quite encouraging and confirmed to be 99.65 and 99.69%, respectively. Accordingly, the resulting behavior of LC-TiO2 towards 68Ge/68Ga adsorption/desorption capacity and stability with aqueous HCl exhibited a high potential for ion-exchange solid-phase extraction for the 68Ge/68Ga generator column material.
Background: Rhein, an anthraquinone derivative, and gold nanoparticles have demonstrated significant potential in facilitating the theranostics of breast cancer. Rhein inhibits breast cancer by exhibiting a strong binding affinity to the estrogen receptor. In addition, gold nanoparticles, when used as nanocarriers, may enhance the therapeutic effects against breast cancer. This study out-lines the preparation of [124I]rhein-gold for position emission tomography (PET) imaging in a breast cancer mouse model. Method: Gold nanoparticles (30 nm) were prepared using the citrate reduction method. Second, the anthraquinone derivative rhein-cysteine complex was synthesized using the carbodiimide coupling method. Third, the radiosynthesis of [124I]rhein-Cys-gold nanocomposites (RCGs) was performed using the chloramine T method. Specifically, 1 mg of RCGs in dimethylformamide was mixed with Na124I (37 MBq) at pH 12 along with chloramine T (5 mg). The reaction was allowed to proceed for 15 min at room temperature. To remove free 124I, the mixture was purified via centrifugation for 10 min at 10,000 rpm. Results: The radiochemical yield of [124I]RCGs was 65% ± 8.2%, with a radiochemical purity of > 98%. In vivo [124I]RCGs targeted MCF-7 cells in a hormone-dependent manner, with cellular uptake values of 25.4 ± 1.59% at 15 min, 27.1 ± 1.27% at 30 min, 28.6 ± 0.38% at 60 min, and 15.97 ± 0.66% at 120 min. In vivo small-animal PET images of [124I]RCGs showed significant uptake in human breast cancer and MCF-7 tumors. Conclusion: This study demonstrated the synthesis and biological evaluation of [124I]RCGs. [124I]RCGs showed high cellular uptake in a time-dependent manner. PET images of [124I]RCGs confirmed their high affinity for MCF-7 tumors in mice from 1 h to 24 h. These results suggest that [124I]RCGs are promising radiopharmaceuticals, demonstrating potential both as an imaging agent and therapeutic option for estrogen-receptor-targeted breast cancer treatment.