A new modality in targeted delivery of epirubicin for tumor theranosis based on PEGylated silver nanoparticles: Design, radiolabeling and bioevaluation.

This work highlights boosting the tumor targeting efficiency of epirubicin through loading on a new radionanosystem, based on the effective role of silver nanoparticles (AgNPs). Accordingly, PEGylated silver nanoparticles (PEG/AgNPs) were prepared in a size of 20.2 ± 0.1 nm. Additionally, epirubicin was loaded on PEG/AgNPs with a loading efficiency of 63 ± 3 %. Furthermore, both of PEG/AgNPs and EPI/PEG/AgNPs were radiolabeled with 131I isotope with radiolabeling yields of 85 ± 0.2 % and 90.3 ± 1 %, respectively. The in-vivo distribution of 131I-PEG/AgNPs and 131I-EPI/PEG/AgNPs were examined in healthy and tumor bearing mice models. Excitingly, 131I-EPI/PEG/AgNPs revealed a reticuloendothelial system (RES) avoidance and prolonged circulating time. In addition, 131I-EPI/PEG/AgNPs showed fast targeting of tumor site by 25.1 ± 0.1 %ID/g within 0.5 h after intravenous injection. Subsequently, the outcomes provided 131I-EPI/PEG/AgNPs as a new potential system for enhancement of tumor targeting and theranosis (therapy and/or imaging).

Improvement of doxorubicin radioiodination and in-vivo cancer suppression via loading in nanosilver system.

This study aimed at improving the radioiodination of doxorubicin (DOX) and its localization in cancer cell for theranostic purposes. To achieve this goal, a composite of DOX with polyvinyl pyrrolidone (PVP) and silver nanoparticles (AgNPs) was prepared. Both DOX and (DOX/PVP/AgNPs) were radiolabelled with iodine-125 [125I] and optimized using iodogen as a preferable oxidizing agent. The maximum obtained radiochemical yields for both systems were 79.9% and 96.6%, respectively. Interestingly, the biodistribution study revealed that [125I]DOX/PVP/AgNPs had an effective localization on tumors. Moreover, Target/control target (T/CT) ratio of [125I] DOX/PVP/AgNPs showed the highest value of 9.1 at 1 h post injection, suggesting that [125I]DOX/PVP/AgNPs has a great potential as a proposed tumor targeting agent.

Investigation for anticancer activity of the newly synthesized p-Methoxyphenyl maleanilic acid and the diagnostic property of its 99mTc-analogue.

PURPOSE: The limitations of the current chemotherapeutics are the main rational to develop and/or explore new anticancer agents and radiolabeled analogues for cancer early diagnosis. MATERIALS AND METHODS: The newly synthesized p-methoxyphenyl maleanilic acid (MPMA) was prepared, characterized and investigated for its anticancer activity. MPMA screened in-vitro against human hepatocellular carcinoma (HepG-2), human colon carcinoma (HCT-116) and human breast carcinoma (MCF-7) cell lines. Furthermore, the in-vivo screening was performed by radiolabeling of MPMA with technetium-99m (99mTc) and investigating its biological distribution in normal mice and solid tumor models. Moreover, MPMA and its radiolabeled analogue were docked to Y220C and Y220S mutants of p53 (p53Y220C and p53Y220S) in an effort to confirm their affinity to cancer as well as to investigate, virtually, the mechanism of action of MPMA. RESULTS: The results revealed significant potency of MPMA against HepG-2 cell line (IC50 = 56.2 ± 1.5 µg/mL) if compared to HCT-116 (IC50 = 89.9 ± 1.8 µg/mL) and MCF-7 (IC50 = 104 ± 2.7 µg/mL) cell lines. The radiolabeling yield was optimized to be 90.2 ± 2.1%. The radiolabeled MPMA showed a good localization in the site of solid tumor (15.1 ± 1.6%ID/g) at 2 h post intravenous administration to the tumor bearing mice. CONCLUSIONS: Collectively, the findings confirmed the potential anticancer activity of MPMA and the possible use of 99mTc-MPMA for cancer diagnosis and monitoring.

Biological Screening and Radiolabeling of Raptinal as a Potential Anticancer Novel Drug in Hepatocellular Carcinoma Model.

New synthetic compound Raptinal (RAP) was investigated on different biological levels for its potential anticancer activity. RAP showed higher antiproliferative activity on HepG2 cell line with IC50 0.62µM compared to MCF-7 and HCT-116 (4.03 and 92.3 µM) respectively. Moreover, RAP induces early stage of apoptosis in the most sensitive HepG2 treated cells after 24 hr with cell cycle arrest in both subG0-G1 and G0-G1 phases and minimal cell count in G2/M mitotic phase with apoptotic index 9.25-fold higher than to control. RAP induces over-expression of key apoptotic genes such as Fas receptor, Caspase-8, Caspase-9, Bax and P53. Western blotting confirm the observation on protein level via over-expression of Caspase-9, Cytochrome-C and higher ration of Bax/Bcl-2. In addition, RAP was radiolabeled using one of the most important diagnostic radioactive isotopes, technetium-99m (99mTc), with a radiochemical yield of 92.7 ± 0.41 %. Quality control and biological distribution of 99mTc-RAP in both healthy and HCC rat model were investigated. Biodistribution profile revealed the localization of RAP in liver tissues (20.5±2.6 %) of HCC models at half an hour post intravenous injection. Histopathological examination confirmed the biodistribution of RAP into liver tissue with induction of karyomegaly in the nuclei of hepatocytes as well as others that proceeded into apoptosis. Molecular docking suggested RAP binds in binding pocket of p53 cancer mutant Y220C making reactivation of the mutant form which is a promising strategy for further investigation on molecular level as a novel anticancer therapeutics. All the results support the use of RAP as a potential anticancer drug in HCC and its 99mTc complex as an imaging probe.

Enhancing Tumor Targeting Efficiency of Radiolabeled Uridine (via) Incorporation into Nanocubosomal Dispersions.

Background: Several nanosystems are currently being utilized to enhance the targeting efficiency of several cancer chemotherapeutic agents. This study was designed to improve tumor accumulation of iodine-125 (125I)-uridine via incorporation into a nanocubosomal preparation. Materials and Methods: Nanocubosomes were prepared with the aid of Glycerol mono-oleate and Pluronic F127. Each prepared nanocubosomal preparation was adequately characterized by testing their particle size, polydispersity index (PDI), ζ potential (ZP), and transmission electron microscopy. The radiolabeling of uridine with 125I was attempted using several oxidizing agents to achieve a high radiochemical yield, and the factors affecting the reaction yield were studied in detail. A comparative biodistribution study of free 125I-uridine and 125I-uridine loaded nanocubosomes was performed in normal and tumor bearing mice. The biodistribution was evaluated by intravenous injection of the sterile test solution, and animals were anesthetized and dissected at different time intervals postinjection (p.i.). Results: 125I-uridine was obtained in a high radiochemical yield (92.5% ± 0.8%). Afterward, 125I uridine was incorporated in a selected nanocubosome formulation, which showed nanosized cubic particles (178.6 ± 0.90 nm) with PDI (0.301 ± 0.04) and a ZP (34.35 ± 0.4). The biodistribution studies revealed that 125I-uridine nanocubosomes showed higher tumor localization (3.1 ± 0.4%IA/g at 2 h p.i. and a tumor/muscle ratio of 6.2) compared with the free 125I-uridine (2.7% ± 0.4%IA/g at 2 h p.i. and a tumor/muscle ratio of 3.3). Conclusion: The results of this study confirmed that 125I-uridine loaded nanocubosome had better efficiency in targeting the tumor site, which makes it an adequate targeting agent for tumor imaging.

Comparative study on radiolabeling and biodistribution of core-shell silver/polymeric nanoparticles-based theranostics for tumor targeting.

A simple and rapid method for radiolabeling of three types of Ag NPs has been performed using 125I isotope, with high labeling yields, >90% without disturbing the optical properties. All the factors affecting labeling yield were studied. In order to monitor the in-vivo tissue uptake of radiolabeled Ag NPs using γ-rays, Ag-based radioiodo-NPs with a maximum labeling yield were intravenously injected in normal and solid tumor bearing mice. The preliminary biodistribution study revealed that this new radioiodo-NPs have a high affinity to be localized in the tumor site for a long period of time. The reported highly efficient method provides new radiolabeled Ag-based NPs as tumor-specific agents for both diagnostic and therapeutic applications.