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Hydrogels prepared from natural polymers have captured extensive attention over the past decades because of their exceptional biocompatibility and nontoxicity, ease of gelation, and functionalization. Thus, natural polymer hydrogels are considered as promising biomaterials that show great potential in the biomedical field. In drug-delivery systems, the extent and the rate with which the drugs reach their targets are highly carrierdependent, so the demand for intelligent drug-delivery systems is gradually increasing. Recently, natural polymer hydrogels functionalized with magnetic materials have been used as a novel smart response device for drug delivery because of the quick response and remote controllability. This review aims to give the latest advances of magnetic hydrogels based on natural polymers such as polysaccharide, protein, and DNA in drug-delivery systems. Specifically, the first part compares several general synthesis strategies of magnetic natural polymer hydrogels. The applications of magnetic natural polymer hydrogels are described in the second part. For the last part, an overview of the application in drug delivery for the magnetic hydrogels constructed from several representative natural polymers is presented.

The measurement of receptor occupancy (RO) using positron emission tomography (PET) has been instrumental in guiding discovery and development of CNS directed therapeutics. We and others have investigated muscarinic acetylcholine receptor 4 (M4) positive allosteric modulators (PAMs) for the treatment of symptoms associated with neuropsychiatric disorders. In this article, we describe the synthesis, in vitro, and in vivo characterization of a series of central pyridinerelated M4 PAMs that can be conveniently radiolabeled with carbon-11 as PET tracers for the in vivo imaging of an allosteric binding site of the M4 receptor. We first demonstrated its feasibility by mapping the receptor distribution in mouse brain and confirming that a lead molecule 1 binds selectively to the receptor only in the presence of the orthosteric agonist carbachol. Through a competitive binding affinity assay and a number of physiochemical properties filters, several related compounds were identified as candidates for in vivo evaluation. These candidates were then radiolabeled with 11 C and studied in vivo in rhesus monkeys. This research eventually led to the discovery of the clinical radiotracer candidate [ 11 C]MK-6884.

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