Feasibility and therapeutic potential of [177Lu]Lu-FAPI-2286 in patients with advanced metastatic sarcoma.

INTRODUCTION: The unique expression pattern of fibroblast activation protein (FAP) in stromal and tumor cells, particularly in sarcomas, and its absence in normal tissues, have positioned it as a promising theragnostic approach for the detection and treatment of various cancer types. The objective of this prospective study is to assess the feasibility, safety, biodistribution, and therapeutic efficacy of [177Lu]Lu-FAPI-2286 in patients with advanced metastatic sarcoma. PATIENTS AND METHODS: Eight patients with advanced metastatic sarcoma, who were unresectable or had experienced disease recurrence following conventional treatments, underwent PTRT (peptide-targeted radionuclide therapy) using [177Lu]Lu-FAPI-2286. Prior to the treatment, confirmation of tumor uptake was obtained through [68Ga]Ga-FAPI-2286 PET/CT. RESULTS: After four cycles of PTRT with [177Lu]Lu-FAPI-2286 (6660-7400 MBq), with a 6-8-week interval between each cycle, no grade 3 or 4 side effects were observed in the patients, and the treatment was well tolerated by all participants. The results demonstrated a 52.37% reduction in the average volume of the primary tumor, accompanied by a significant decrease in SUVmax and TBR of the metastatic lesions (29.67% and 43.66% respectively), especially in cases of lung metastasis. Furthermore, besides the improvement in physical capacity, there was a noticeable reduction in pain, an increase in overall survival, and enhanced satisfaction with the treatment reported by the patients. CONCLUSION: [177Lu]Lu-FAPI-2286 PTRT, utilized for diverse cancer types, exhibited favorable tolerability in sarcoma patients, with minimal side effects, long-lasting retention of the radiopeptide within the tumor, and promising therapeutic effects. Preliminary findings of this prospective study need to be confirmed through further clinical trials.

Novel Biocompatible Amino Acids-Functionalized Three-dimensional Graphene Foams: As the Attractive and Promising Cisplatin Carriers for Sustained Release Goals.

Application of amino acids-immobilized porous materials for drug delivery studies has been attracted a lot of attention in the recent years. In this study, amino acids-grafted graphene foams were prepared by anchoring of Alanine (Ala), Cysteine (Cys) and Glycine (Gly) amino acids on the surface of graphene oxide (GO) nanostructures and used as the novel biocompatible carriers to control releasing of the cisplatin as the cytotoxic anticancer drug. The characterization of prepared compounds was done by the FT-IR, Raman, TGA, N2 adsorption-desorption isotherms, SEM, and TEM techniques. Adsorption and in vitro release behavior of amino acids-functionalized foams were studied using ICP standard method. The results show that the drug loading amount and the drug releasing rate are significantly enhanced upon functionalization process. The Ala-Foam sample with the larger surface area and pore volume showed a higher loading content (4.53%) than other samples. In addition, the MTT test on the two MCF-7 and HepG2 human cancer cell lines exhibited an acceptable biocompatibility and sustainable drug releasing from the carriers up to 48 h, leading to the dosage frequency decrease and the patient compliance improvement.

Amino Acid-functionalized hollow mesoporous silica nanospheres as efficient biocompatible drug carriers for anticancer applications.

Herein, a series of new amino acid-functionalized hollow mesoporous silica nanospheres (HMSNs) by post-grafting methods were prepared. These new materials were characterized by different techniques and were studied as matrices for the antineoplastic drug (cisplatin) transport and delivery. The results demonstrate that the surface functionalization of the carriers has a remarkable positive influence on the loading efficiency and release rate of cisplatin. The highest drug entrapment efficiency and the most optimal release properties were observed when the (2-(butylamino) ethyl) glycine groups are grafted on the HMSNs surface (AFS-2-HMSNs sample). Moreover, the in vitro cytotoxic effect of both empty and cisplatin-loaded AFS-2-HMSNs sample (CDDP@AFS-2-HMSNs) on MCF-7 cells (human breast adenocarcinoma cell line) and HepG2 cells (human liver carcinoma cell line) were evaluated by MTT assay. The most important outcome is that the empty carrier revealed no cytotoxicity to cancer cells. However, CDDP@AFS-2-HMSNs caused a notable inhibition of cell viability which was affected from the dose and time. Our results demonstrate that the synthesized materials could be used as carriers for drug delivery with controlled release applications.

Photodegradation of 2,4-dichlorophenol by supported Pd(X2) catalyst (X = Cl, Br, N3): a HOMO manipulating point of view.

Three different palladium(II) complexes with ligands containing nitrogenized aromatic rings were investigated theoretically as model to obtain the computational band gap energies. The results demonstrated promising possibility for designing palladium(II) complexes with photocatalytic properties at visible light irradiation. Deliberated products were synthesized via grafting on the silica-coated Fe3O4 magnetic nanoparticles (Fe3O4@SiO2). Formation of complexes on the surface of Fe3O4@SiO2, as insoluble and reusable photocatalysts, was proved by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), thermogravimetric (TGA), X-ray photoelectron spectroscopy (XPS), vibrating sample magnetometer (VSM), transmission electron microscope (TEM), and scanning electron microscopy (SEM) analyses. The trend of the band gap energies of prepared structures was calculated via experimental and theoretical methods. The photocatalytic capability of these nanoparticles was investigated in degradation of 2,4-dichlorophenol by means of HPLC analysis. A tentative reaction mechanism for the formation of intermediates was proposed. Graphical abstract ᅟ.

Synthesis, cytotoxicity assessment, and interaction and docking of novel palladium(II) complexes of imidazole derivatives with human serum albumin.

Imidazole analogs are the agents that attract both bioinorganic chemist and drug designer. Numerous methods have been proposed for synthesis of imidazole derivatives. In this study, a series of heterocyclic system with p-conjugated system such as 2-aryl-imidazo[4,5-f][1,10]phenanthroline analogs were synthesized. Then, three new palladium(II) complexes containing 2-(Furan-2-yl)-1H-Imidazo[4,5-f][1,10]Phenanthroline (FIP) and 2-(thiophen-2-yl)-1H-imidazo[4,5-f][1,10]phenanthroline (TIP) ligands were synthesized. The structures of the compounds, [Pd(Phen)(TIP)](NO3)2, [Pd(Phen)(FIP)](NO3)2, and [Pd(FIP)2]Cl were determined by spectroscopic methods and elemental analysis. Biological activity of the complexes synthesized was assessed against chronic myelogenous leukemia cell line, K562. Also, the interactions of human serum albumin with complexes were investigated using isothermal titration in the Tris buffer, pH 7.4. According to the results obtained, it was found that there is a set of six binding sites for these complexes on HSA with positive cooperativity in the binding process. Docking technique was also applied to confirm the experimental results. The results showed that smaller complexes have higher interaction affinity.