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 89 Zr 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, 89 Zr-labelled HMSNs with the markedly reduced 89 Zr release. Rm camouflaged 89 Zr-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.

The Ga is a positron-emitting radionuclide that can be combined with bifunctional chelating agents and bioactive substances for use as positron-emission tomography (PET) diagnostic agents. The HBED-CC is an acyclic chelating agent that is rapidly labeled with Ga under mild conditions. To target cancer cells, bioactive substances can be conjugated to the carboxyl terminus of HBED-CC. Because folic acid strongly binds to folate receptors that are overexpressed on the surfaces of many types of cancer cells, it was coupled with HBED-CC through a small polyethylene glycol-based linker (EDBE) to generate an active, receptor-selective targeting system. The HBED-CC-EDBE-folate (HCEF) precursor was readily labeled with Ga in 5 minutes at room temperature (98% radiochemical yield; 99% radiochemical purity after isolation). In cellular uptake tests, higher uptakes of Ga-HCEF were observed for the CT26 and KB cell lines (which express folate receptors) than for the A549 cell line (which does not). Finally, in vivo micro-PET measurements over 2 hours of binding in BALB/c mice into which CT26 tumors had been transplanted showed the selective accumulation of Ga-HCEF in the folate receptor-expressing CT26 tumors. These results confirmed the potential of Ga-HCEF as a PET diagnostic agent for tumors that express folate receptors.

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.

Cherenkov radiation (CR) derived from the decay of diagnostic and therapeutic radionuclides is currently being studied by the scientific community to determine if these emissions can be harnessed for cancer detection and therapy. While Cherenkov luminescence imaging (CLI) has been studied in the preclinical and clinical settings, Cherenkov radiation-induced cancer therapy (CRICT) is a relatively new area of research that harnesses the emitted photons to kill cancer cells through free radical generation and DNA damage. Nanoparticles seem well suited for developing a theranostic platform that would allow researchers to visualize therapy delivery and also generate the reactive oxygen species necessary to kill cancer cells. Herein, we report the preparation of an 89Zr–TiO2–MnO2 nanocomposite that incorporates transferrin onto the nanoparticle surface to enhance cancer cell growth inhibition. The incorporation of the positron emission tomography (PET) radioisotope 89Zr (half-life: 3.3 days) allowed for the detection of the nanoparticle using PET and for the creation of Cherenkov emissions that interacted with the nanoparticle surface to generate free radicals for therapy delivery. After preparation, these systems were observed to be stable in various media and provided excellent tumor growth control after being intratumorally injected into mice bearing CT-26 tumors. These results demonstrate that a therapeutically efficient CRICT platform can be generated using commercially available and affordable materials.