We synthesized and evaluated a novel class of chelator-free [ 64 Cu]-CuS nanoparticles (NPs) suitable for both PET imaging and as photothermal coupling agents for photothermal ablation.[ 64 Cu]-CuS NPs were simple to make, possessed excellent stability, and allowed robust noninvasive micro-PET imaging. Furthermore, CuS NPs displayed strong absorption in the nearinfrared (NIR) region (peak 930 nm), passive targeting prefers the tumor site, and mediated ablation of U87 tumor cells upon exposure to NIR light both in vitro and in vivo after either intratumoral or intravenous injection. The combination of small diameter (~11 nm diameter), strong NIR absorption, and integration of 64 Cu as a structural component makes [ 64 Cu]-CuS NPs ideally suited for multifunctional molecular imaging and therapy.

Polyethylene glycol (PEG)-coated (pegylated) gold nanoparticles (AuNPs) have been proposed as drug carriers and diagnostic contrast agents. However, the impact of particle characteristics on the biodistribution and pharmacokinetics of pegylated AuNPs is not clear. We investigated the effects of PEG molecular weight, type of anchoring ligand, and particle size on the assembly properties and colloidal stability of PEG-coated AuNPs. The pharmacokinetics and biodistribution of the most stable PEG-coated AuNPs in nude mice bearing subcutaneous A431 squamous tumors were further studied using 111 In-labeled AuNPs. AuNPs coated with thioctic acid (TA)-anchored PEG exhibited higher colloidal stability in phosphate-buffered saline in the presence of dithiothreitol than did AuNPs coated with monothiol-anchored PEG. AuNPs coated with high-molecular-weight (5000 Da) PEG were more stable than AuNPs coated with low-molecular-weight (2000 Da) PEG. Of the 20-nm, 40-nm, and 80-nm AuNPs coated with TA-terminated PEG 5000 , the 20-nm AuNPs exhibited the lowest uptake by reticuloendothelial cells and the slowest clearance from the body. Moreover, the 20-nm AuNPs coated with TA-terminated PEG 5000 showed significantly higher tumor uptake and extravasation from the tumor blood vessels than did the 40-and 80-nm AuNPs. Thus, 20-nm AuNPs coated with TA-terminated PEG 5000 are promising potential drug delivery vehicles and diagnostic imaging agents.

Ischemic stroke is a devastating disease and one of the leading causes of mortality worldwide. Overproduction of reactive oxygen and nitrogen species (RONS) following ischemic insult is known as a key factor in exacerbating brain damage. Thus, RONS scavengers that can block excessive production of RONS have great therapeutic potential. Herein, we propose an efficient treatment strategy in which an artificial nanozyme with multienzyme activity drives neuroprotection against ischemic stroke primarily by scavenging RONS. Specifically, through a facile, Bi 3+ -assisted, template-free synthetic strategy, we developed hollow Prussian blue nanozymes (HPBZs) with multienzyme activity to scavenge RONS in a rat model of ischemic stroke. The comprehensive characteristics of HPBZs against RONS were explored. Apart from attenuating oxidative stress, HPBZs also suppressed apoptosis and counteracted inflammation both in vitro and in vivo, thereby contributing to increased brain tolerance of ischemic injury with minimal side effects. This study provides a proof of concept for a novel class of neuroprotective nanoagents that might be beneficial for treatment of ischemic stroke and other RONS-related disorders.

Alzheimer's disease (AD) remains an incurable disease and lacks efficient diagnostic methods. Most AD treatments have focused on amyloid-β (Aβ) targeted therapy; however, it is time to consider the alternative theranostics due to accumulated findings of weak correlation between Aβ deposition and cognition, as well as the failures of Phase III clinical trial on Aβ targeted therapy. Recent studies have shown that the tau pathway is closely associated with clinical development of AD symptoms, which might be a potential therapeutic target. We herein construct a methylene blue (MB, a tau aggregation inhibitor) loaded nanocomposite (CeNC/IONC/MSN-T807), which not only possesses high binding affinity to hyperphosphorylated tau but also inhibits multiple key pathways of tau-associated AD pathogenesis. We demonstrate that these nanocomposites can relieve the AD symptoms by mitigating mitochondrial oxidative stress, suppressing tau hyperphosphorylation, and preventing neuronal death both in vitro and in vivo. The memory deficits of AD rats are significantly rescued upon treatment with MB loaded CeNC/IONC/MSN-T807. Our results indicate that hyperphosphorylated tau-targeted multifunctional nanocomposites could be a promising therapeutic candidate for Alzheimer's disease.

Copper based nanoparticles (NPs) have attracted increased attention for biomedical applications. Copper chalcogenide NPs exhibit strong absorption in near-infrared region, demonstrate highly efficient light-to-heat transformation under near-infrared laser irradiation, and cause selective thermal destruction to the tumor. Smaller copper NPs display fluorescence signal and capability for optical imaging. Copper based NPs also serve as a versatile vehicle for drug delivery and image-guided therapy. This review covers recent advances related to the biomedical application of copper based NPs, with a focus on cancer imaging and therapy. We also discuss challenges to their successful clinical translation.

The first small-molecule based αvβ3-targeted NIR-II/PET dual-modal probes via base-catalyzed thiol-addition chemistry were concisely assembled and evaluated.

Obesity, defined as body mass index greater than 30, is a leading cause of morbidity and mortality and a financial burden worldwide. Despite significant efforts in the past decade, very few drugs have been successfully developed for the treatment of obese patients. Biological differences between rodents and primates are a major hurdle for translation of anti-obesity strategies either discovered or developed in rodents into effective human therapeutics. Here, we evaluate the ligand-directed peptidomimetic CKGGRAKDC-GG-D(KLAKLAK)2 (henceforth termed adipotide) in obese Old World monkeys. Treatment with adipotide induced targeted apoptosis within blood vessels of white adipose tissue and resulted in rapid weight loss and improved insulin resistance in obese monkeys. Magnetic resonance imaging and dual-energy x-ray absorptiometry confirmed a marked reduction in white adipose tissue. At experimentally determined optimal doses, monkeys from three different species displayed predictable and reversible changes in renal proximal tubule function. Together, these data in primates establish adipotide as a prototype in a new class of candidate drugs that may be useful for treating obesity in humans.

Radiolabeled bombesin (BBN) analogs that bind to the gastrin-releasing peptide receptor (GRPR) represent a topic of active investigation for the development of molecular probes for PET or SPECT of prostate cancer (PCa). RM1 and AMBA have been identified as the 2 most promising BBN peptides for GRPR-targeted cancer imaging and therapy. In this study, to develop a clinically translatable BBN-based PET probe, we synthesized and evaluated 18F-AlF- (aluminum-fluoride) and 64Cu-radiolabeled RM1 and AMBA analogs for their potential application in PET imaging of PCa. Methods 1,4,7-triazacyclononane, 1-glutaric acid-4,7 acetic acid (NODAGA)–conjugated RM1 and AMBA were synthesized and tested for their GRPR-binding affinities. The NODAGA-RM1 and NODAGA-AMBA probes were further radiolabeled with 64Cu or 18F-AlF and then evaluated in a subcutaneous PCa xenograft model (PC3) by small-animal PET imaging and bio-distribution studies. Results NODAGA-RM1 and NODAGA-AMBA can be successfully synthesized and radiolabeled with 64Cu and 18F-AlF. 64Cu- and 18F-AlF-labeled NODAGA-RM1 demonstrated excellent serum stability and tumor-imaging properties in the in vitro stability assays and in vivo imaging studies. 64Cu-NODAGA-RM1 exhibited tumor uptake values of 3.3 ± 0.38, 3.0 ± 0.76, and 3.5 ± 1.0 percentage injected dose per gram of tissue (%ID/g) at 0.5, 1.5, and 4 h after injection, respectively. 18F-AlF-NODAGA-RM1 exhibited tumor uptake values of 4.6 ± 1.5, 4.0 ± 0.87, and 3.9 ± 0.48 %ID/g at 0.5, 1, and 2 h, respectively. Conclusion The high-stability, efficient tumor uptake and optimal pharmacokinetic properties highlight 18F-AlF-NODAGA-RM1 as a probe with great potential and clinical application for the PET imaging of prostate cancer.