Spherical nucleic acids (SNAs) are composed of a nanoparticle core and a layer of densely arranged oligonucleotide shells. After the first report of SNA by Mirkin and coworkers in 1996, it has created a significant interest by offering new possibilities in the field of gene and drug delivery. The controlled aggregation of oligonucleotides on the surface of organic/inorganic nanoparticles improves the delivery of genes and nucleic acid–based drugs and alters and regulates the biological profiles of the nanoparticle core within living organisms. Here in this review, we present an overview of the recent progress of SNAs that has speeded up their biomedical application and their potential transition to clinical use. We start with introducing the concept and characteristics of SNAs as drug/gene delivery systems and highlight recent efforts of bioengineering SNA by imaging and treatmenting various diseases. Finally, we discuss potential challenges and opportunities of SNAs, their ongoing clinical trials, and future translation, and how they may affect the current landscape of clinical practices. We hope that this review will update our current understanding of SNA, organized oligonucleotide aggregates, for disease diagnosis and treatment.
Purpose: 68 Ga-labeled fibroblast activation protein inhibitor ( 68 Ga-FAPI-04) has been useful in the imaging of desmoplastic reaction in different tumors. As we have found that most female patients showed avid uterine uptake of 68 Ga-FAPI-04, we sought to further investigate the pathological and physiological uptake of 68 Ga-FAPI-04 characteristics in the uterus. Patients and Methods: We reviewed the image data of female patients who had undergone 68 Ga-FAPI-04 PET/MRI at our institute between May 22, 2020, and June 21, 2021. The characteristics of uterine uptake and clinical information were collected. The uterus with and without malignancy were compared. We further analyzed the relationship of age, uterus size, gynecological history, and 18 F-FDG uptake (if performed) with 68 Ga-FAPI-04 uptake. Results: Seventy-seven patients were included in this study. Much higher cervical 68 Ga-FAPI-04 accumulation was noticed in cervical cancer patients than in normal cases, and 37 more metastases were found in 68 Ga-FAPI-04 PET than that in 18 F-FDG. Uterine body malignancies displayed different uptake features. Two cases with the metastases to uterine body showed relative lower 68 Ga-FAPI-04 activity compared with their normal uteri. Of 67 patients without malignancy, lower 68 Ga-FAPI-04 uptake was noted in postmenopausal women than in reproductive and perimenopausal patients. The invasive operation or hysteromyoma may increase 68 Ga-FAPI-04 uptake. Conclusions: 68 Ga-FAPI-04 PET might be a promising method in cervical cancers. However, physiological uptake may limit its diagnostic value in uterine body malignancy. It should be noticed that the metastatic lesion in the uterus may show relative lower uptake of 68 Ga-FAPI-04 compared with the rest of the uterus. Age, fibroids, and uterine volume may influence 68 Ga-FAPI-04 uptake in the uterus. More patients with various uterine diseases could be involved to provide more differential diagnostic information.
18 F-FDG PET has limited diagnostic applications in malignant melanoma (MM). 18 F-PFPN is a novel PET probe with high affinity and selectivity for melanin. We conducted a clinical study with two aims, firstly to investigate the biodistribution and radiation dosimetry of 18 F-PFPN in healthy volunteers, and secondly, to examine the diagnostic utility of 18 F-PFPN PET imaging in patients with MM. Methods: 18 F-PFPN was synthesized through a fluoro-for-tosyl exchange reaction. Five healthy volunteers were enrolled to investigate the biodistribution, pharmacokinetics, radiation dosimetry, and safety of the tracer. Subsequently, a total of 21 patients with clinically suspected or confirmed MM underwent both 18 F-PFPN PET/MR and 18 F-FDG PET/CT scans. Normalized maximum standardized uptake values of selected lesions were determined for both tracers and compared in patient-and lesion-based analyses. Results: 18 F-PFPN has elevated radiochemical yield and was highly stable in vivo. In healthy volunteers, 18 F-PFPN was safe and welltolerated and its effective absorbed dose was comparable to that of 18 F-FDG. In patient-based analysis, 18 F-PFPN uptake was higher than 18 F-FDG for both primary tumors and nodal metastases. In lesion-based analysis, 18 F-PFPN PET imaging could detect 365 metastases that were missed on 18 F-FDG PET. Additionally, 18 F-PFPN PET imaging had clinical value in distinguishing false-positive lesions on 18 F-FDG PET. Conclusion:18 F-PFPN is a safe and well-tolerated melanin PET tracer. In a pilot clinical study, 18 F-PFPN PET imaging outperformed traditional 18 F-FDG PET in identifying both primary MM and its distant spread.
Heart failure (HF) is a chronic and progressive clinical syndrome with structure or functional abnormalities of the heart. Active broblasts and ventricular remodeling play an essential role in the progression of HF. 68 Ga-labeled broblast activating protein inhibitor ( 68 Ga-FAPI) have been proved binding with broblast activation protein (FAP) in many diseases. This study aimed to use 68 Ga-FAPI PET to continuously visualize the dynamic change process of cardiac broblasts and HF to aid in the clinical management of HF. MethodsThe rat model of HF was established by injection of isoproterenol for 14 d continuously. Echocardiography and 68 Ga-FAPI were performed weekly. Isolated hearts were taken every week for biodistribution, autoradiography, hematoxylin-eosin, FAP-immuno uorescence and Masson's trichrome staining, and blood samples for enzyme-linked immunosorbent assay. A preliminary study of HF patients further recruited for 13 N-amino ( 13 N-NH 3 ) perfusion and 68 Ga-FAPI cardiac PET imaging simultaneously. ResultsExtensive myocardial uptake of 68 Ga-FAPI, expression of FAP, and myocardial contractility peaked at 7 d after the onset of modeling, while only slight brotic changes were manifested. With time extension, 68 Ga-FAPI uptake and ventricular wall motion of the heart reduced, while cardiac brosis and degree of myocardial injury gradually increased. Seven patients diagnosed with HF were successfully enrolled (5 men and 2 women, 58.14 ± 16.25 years). 13 N-NH 3 perfusion was inconsistent with 68 Ga-FAPI uptake. Higher myocardial 68 Ga-FAPI uptake was demonstrated in the patients with < 1-year duration than other groups. ConclusionWith the progress of HF, 68 Ga-FAPI accumulates evidently in the early stage, and gradually reduced. Preliminary clinical study suggested that 68 Ga-FAPI PET could be used to display active brosis. Active myocardial FAP expression is followed by myocardial remodeling and myocardial brosis, suggesting that the detection of early active FAP expression may help guiding anti brotic-drug therapy.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
334 Leonard St
Brooklyn, NY 11211
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.