BACKGROUND: In this study, a combination of nanotechnology, organic synthesis and radiochemistry were utilized in order to design an efficient nano-system conjugated with a suitable radionuclide and an antitumor agent for possible application as tumor theragnostic agent.
METHODS: Four novel compounds (3 and 4a-c) bearing tetrahydroquinazoline-7-sulfonohydrazide or 1,2,3,4-tetrahydroquinazoline-7-sulfonamide scaffold were designed. Then, docking study predicted that the compounds can be considered as potential inhibitors for PARP-1. Following that; the four compounds were synthesized and properly characterized using 1HNMR, 13CNMR, IR and Mass spectroscopy. The cytotoxic effect of the four compounds was evaluated against breast cancer cell line (MDA-MB-436), where compound 3 showed the most promising cytotoxic effect. The inhibitory effect of the four compounds was evaluated in vitro against PARP-1.
RESULTS: Carboxylated graphene oxide nanosheets (NGO-COOH) were synthesized by a modified Hummer\'s method and has size of range 40 nm. The NGO-COOH nanosheets were proven to be safe and biocompatible when tested in vitro against normal human lung fibroblast cells (MRC-5). The prepared NGO-COOH nanosheets were conjugated with compound 3 then radiolabeled with 99mTc to yield 99mTc-NGO-COOH-3 with a radiochemical yield of 98.5.0 ± 0.5%. 99mTc-NGO-COOH-3 was injected intravenously in solid tumor bearing mice to study the degree of localization of the nano-system at tumor tissue. The results of the study revealed, excellent localization and retention of the designed nano-system at tumor tissues with targeting ratio of 9.0.
CONCLUSIONS: Stirred a new candidate tumor theragnostic agent that is safe, selective and stable.

Aptamers are oligonucleotides that have the characteristic of recognizing a target with high affinity and specificity. Based on our previous studies, the aptamer probe Sgc8-c-Alexa647 is a promising tool for molecular imaging of PTK7, which is an interesting biomarker in cancer. In order to improve the delivery of this probe as well as create a novel drug delivery nanosystem targeted to the PTK7 receptor, we evaluate the co-association between the probe and preformed nanostructures. In this work, preformed pegylated liposomes (PPL) and linear and branched pristine polymeric micelles (PMs), based on PEO-PPO-PEO triblock copolymers were used: poloxamer F127® and poloxamines T1307® and T908®. For it, Sgc8-c-Alexa647 and its co-association with the different nanostructures was exhaustively analyzed. DLS analysis showed nanometric sizes, and TEM and AFM showed notable differences between free- and co-associated probe. Likewise, all nanosystems were evaluated on A20 lymphoma cell line overexpressing PTK7, and the confocal microscopy images showed distinctness in cellular uptake. Finally, the biodistribution in BALB/c mice bearing lymphoma-tumor and pharmacokinetic study revealed an encouraging profile for T908-probe. All data obtained from this work suggested that PMs and, more specifically T908 ones, are good candidates to improve the pharmacokinetics and the tumor uptake of aptamer-based probes.

OBJECTIVE: Cantharidin (CTD), the major component of the anti-cancer medicine obtained from Mylabris cichorii, exerts good inhibitory effects on several cancers, such as liver and breast cancer. However, owing to its toxicity, its oral administration can cause various adverse effects, limiting its clinical applications. Therefore, the development of a novel nano-drug delivery system for CTD would be highly beneficial.
METHODS: A nanostructured lipid carrier (NLC) was designed to actively target CTD to tumor cells using a hyaluronic acid (HA)-decorated copolymer (mPEG-NH2); the NLCs were called HA-mPEG-CTD-NLC. HA-mPEG was synthesized using amidation, and HA-mPEG-CTD-NLC was generated through ultrasonic emulsification in water. The mean hydrodynamic diameter of the particles was approximately 119.3 nm.
RESULTS: Pharmacokinetic studies revealed that the half-life of HA-mPEG-CTD-NLC and its area under the curve were higher than those of a CTD solution. Further, the plasma clearance rate of HA-mPEG-CTD-NLC was 0.41 times that of the CTD solution, implying a significantly prolonged drug retention time in vivo. Fluorescence in vivo endo-microscopy and optical in vivo imaging revealed that HA-mPEG-CTD-NLC had superior cytotoxicity and targeting efficacy against SMMC-7721 cells. An evaluation of the in vivo anti-tumor activity showed that HA-mPEG-CTD-NLC significantly inhibited tumor growth and prolonged survival in tumor-bearing mice, with a tumor inhibition rate of 65.96%.
CONCLUSIONS: Our results indicate that HA-mPEG-CTD-NLC may have great potential in liver cancer-targeted therapy.

Although nanoparticle-based photothermal therapy (PTT) has been intensively investigated recently, its comparative efficiency with any clinical cancer treatments has been rarely explored. Herein for the first time we report a systematic comparative study of clinical iodine-125 (125 I) interstitial brachytherapy (IBT-125-I) and interventional PTT (IPTT) in an orthotopic xenograft model of human pancreatic cancer. IPTT, based on the nanoparticles composing of anti-urokinase plasminogen activator receptor (uPAR) antibody, polyethylene glycol (PEG), and indocyanine green (ICG) modified gold nanoshells (hereinafter uIGNs), is directly applied to local pancreatic tumor deep in the abdomen. In comparison to IBT-125-I, a 25% higher median survival rate of IPTT with complete ablation by one-time intervention has been achieved. The IPTT could also inhibit pancreatic tumor metastasis which can be harnessed for effective cancer immunotherapy. All results show that this IPTT is a safe and radical treatment for eradicating tumor cells, and may benefit future clinical pancreatic cancer patients.

We fabricated a targeted delivery system for doxorubicin (Dox) using β-1,3-glucan (Glu) as a carrier and decorated by trastuzumab antibody having the status of targeting agent against Her2+ breast tumors. Glu-Dox conjugates were also functionalized with polyethylenimine (PEI) intended for increasing specific cellular uptake of prepared nanoparticles. The self-assembled nanoparticles were prepared through conjugation of Dox- [Glu-Dox-] using succinic anhydride (Sa) in place of a linker. Nanoparticles had spherical morphology with positive zeta potential. In-vitro cell viability assay on two breast cancer cell lines demonstrated acceptable toxicity against tested cell lines. Confocal microscopic images demonstrated the remarkable cytoplasmic uptake of the nanoparticles in Her2-overexpressing 4T1 cells. A controlled release of Dox from Glu-Dox nanoparticles was investigated. In-vivo studies were performed on female Balb/C mice. The volume of the induced tumors was calculated following intravenous administration of nanoparticles. The tumor volume diminished efficiently and more rapidly after administration of nanoparticles containing Dox. Based on survival results, the formulation of Dox targeted nanoparticles appeared very promising for the treatment of tumors. It could be concluded that Glu-Dox targeted nanoparticles have potential advantages for delivering anticancer drugs to the target tissue.