ABSTRACT
Layered double hydroxide is a family of two-dimensional materials with wide range of compositions. Recently, its ability to accommodate various chemical species and biocompatibility have been attracted in the biomedical applications to develop drug delivery system and nanodiagnostics. In this review, we categorized biomedical approaches of layered double hydroxide with respect to the three topologies of, namely, interlayer space, outer surface with particle edge, and the lattice points. There have been extensive researches on the intercalation of drug or tracing to make use of interlayer space of layered double hydroxide for drug stabilization, sustained release, cellular delivery and etc. Outer surface or edge has been utilized to immobilization of large therapeutic moieties and to attach tracing moiety. Lattice points consisting of various metal species could be utilized for the specific metal species like paramagnetic elements or radioisotopes. Based on these topologies in layered double hydroxide, both the synthetic routes and the achieved functionalities in terms of biomedical application will be discussed.
Subject(s)
Drug Delivery Systems , Hydroxides , Drug Delivery Systems/methods , Humans , Hydroxides/chemistry , MetalsABSTRACT
Heat-shock protein 90 (HSP90) is a molecular chaperone that activates oncogenic transformation in several solid tumors, including lung and breast cancers. Ganetespib, a most promising candidate among several HSP90 inhibitors under clinical trials, has entered Phase III clinical trials for cancer therapy. Despite numerous evidences validating HSP90 as a target of anticancer, there are few studies on PET agents targeting oncogenic HSP90. In this study, we synthesized and biologically evaluated a novel 18F-labeled 5-resorcinolic triazolone derivative (1, [18F]PTP-Ganetespib) based on ganetespib. [18F]PTP-Ganetespib was labeled by click chemistry of Ganetespib-PEG-Alkyne (10) and [18F]PEG-N3 (11) with 37.3⯱â¯5.11% of radiochemical yield and 99.7⯱â¯0.09% of radiochemical purity. [18F]PTP-Ganetespib showed proper LogP (0.96⯱â¯0.06) and good stability in human serum over 97% for 2â¯h. [18F]PTP-Ganetespib showed high uptakes in breast cancer cells containing triple negative breast cancer (TNBC) MDA-MB-231 and Her2-negative MCF-7 cells, which are target breast cancer cell lines of HSP90 inhibitor, ganetespib, as an anticancer. Blocking of HSP90 by the pretreatment of ganetespib exhibited significantly decreased accumulation of [18F]PTP-Ganetespib in MDA-MB-231 and MCF-7 cells, indicating the specific binding of [18F]PTP-Ganetespib to MDA-MB-231 and MCF-7 cells with high HSP90 expression. In the biodistribution and microPET imaging studies, the initial uptake into tumor was weaker than in other thoracic and abdominal organs, but [18F]PTP-Ganetespib was retained relatively longer in the tumor than other organs. The uptake of [18F]PTP-Ganetespib in tumors was not sufficient for further development as a tumor-specific PET imaging agent by itself, but this preliminary PET imaging study of [18F]PTP-Ganetespib can be basis for developing new PET imaging agents based on HSP90 inhibitor, ganetespib.
