Department of Advanced Nuclear Medicine Sciences, The National Institute of Radiological Sciences, The National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan
Prof. Dr. Kuan Hu
Department of Advanced Nuclear Medicine Sciences, The National Institute of Radiological Sciences, The National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan
Peptide-based materials that have diverse structures and functionalities are an important type of biomaterials. In former times, peptide-based nanomaterials with excellent stability were constructed through self-assembly. Compared with individual peptides, peptide-based self-assembly nanomaterials that form well-ordered superstructures possess many advantages such as good thermo- and mechanical stability, semiconductivity, piezoelectricity and optical properties. Moreover, due to their excellent biocompatibility and biological activity, peptide-based self-assembly nanomaterials have been vastly used in different fields. In this review, we provide the advances of peptide-based self-assembly nanostructures, focusing on the driving forces that dominate peptide self-assembly and assembly mechanisms of peptides. After that, we outline the synthesis and properties of peptide-based nanomaterials, followed by the applications of functional peptide nanomaterials. Finally, we provide perspectives on the challenges and future of peptide-based nanomaterials.
3 January 2025 in Signal Transduction and Targeted Therapy
Radiopharmaceuticals involve the local delivery of radionuclides to targeted lesions for the diagnosis and treatment of multiple diseases. Radiopharmaceutical therapy, which directly causes systematic and irreparable damage to targeted cells, has attracted increasing attention in the treatment of refractory diseases that are not sensitive to current therapies. As the Food and Drug Administration (FDA) approvals of [177Lu]Lu-DOTA-TATE, [177Lu]Lu-PSMA-617 and their complementary diagnostic agents, namely, [68Ga]Ga-DOTA-TATE and [68Ga]Ga-PSMA-11, targeted radiopharmaceutical-based theranostics (radiotheranostics) are being increasingly implemented in clinical practice in oncology, which lead to a new era of radiopharmaceuticals. The new generation of radiopharmaceuticals utilizes a targeting vector to achieve the accurate delivery of radionuclides to lesions and avoid off-target deposition, making it possible to improve the efficiency and biosafety of tumour diagnosis and therapy. Numerous studies have focused on developing novel radiopharmaceuticals targeting a broader range of disease targets, demonstrating remarkable in vivo performance. These include high tumor uptake, prolonged retention time, and favorable pharmacokinetic properties that align with clinical standards. While radiotheranostics have been widely applied in tumor diagnosis and therapy, their applications are now expanding to neurodegenerative diseases, cardiovascular diseases, and inflammation. Furthermore, radiotheranostic-empowered precision medicine is revolutionizing the cancer treatment paradigm. Diagnostic radiopharmaceuticals play a pivotal role in patient stratification and treatment planning, leading to improved therapeutic outcomes in targeted radionuclide therapy. This review offers a comprehensive overview of the evolution of radiopharmaceuticals, including both FDA-approved and clinically investigated agents, and explores the mechanisms of cell death induced by radiopharmaceuticals. It emphasizes the significance and future prospects of theranostic-based radiopharmaceuticals in advancing precision medicine.
The 18 kDa translocator protein (TSPO), previously known as the peripheral benzodiazepine receptor, is predominately localized to the outer mitochondrial membrane in steroidogenic cells. Brain TSPO expression is relatively low under physiological conditions, but is upregulated in response to glial cell activation. As the primary index of neuroinflammation, TSPO is implicated in the pathogenesis and progression of numerous neuropsychiatric disorders and neurodegenerative diseases, including Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), multiple sclerosis (MS), major depressive disorder (MDD) and obsessive compulsive disorder (OCD). In this context, numerous TSPO-targeted positron emission tomography (PET) tracers have been developed. Among them, several radioligands have advanced to clinical research studies. In this review, we will overview the recent development of TSPO PET tracers, focusing on the radioligand design, radioisotope labeling, pharmacokinetics, and PET imaging evaluation. Additionally, we will consider current limitations, as well as translational potential for future application of TSPO radiopharmaceuticals. This review aims to not only present the challenges in current TSPO PET imaging, but to also provide a new perspective on TSPO targeted PET tracer discovery efforts. Addressing these challenges will facilitate the translation of TSPO in clinical studies of neuroinflammation associated with central nervous system diseases.
As a novel semiconducting material, the inherent, direct, and appreciable band gap endows BP with preferable optical and electronic properties other than graphene and transition metal dichalcogenides. In addition, bio-related applications with equal importance also attract great attention thanks to several inherited advantages of BP including large drug loading capacity, high PDT efficiency, high biocompatibility and degradability. However, to date there is limited research about the biomedical applications of BP. In this study, we reported the engineering of polyelectrolyte polymers coated BP quantum dots (BP-QDs)-based nanocarriers to deliver small interfering RNA (siRNA) into human ovarian teratocarcinoma PA-1 cells. Compared to the commercial delivery reagents, superior transfection efficiency of BP-QD was detected. The expression of the LSD1 (lysine-specific demethylase 1) mRNA in PA-1 cells was significantly suppressed by BP-QDs-LSD1 siRNA complex. Notably, BP-QDs possess excellent biocompatibility and low cytotoxicity even at concentrations as high as 5 mg mL−1. The combination treatment of BP nanodots-LSD1 siRNA complex with NIR light could inhibit the cell growth rate by more than 80%. In conclusion, this is the first application of BP-QDs as gene delivery systems, which shows promising potential for siRNA delivery and photothermal effects in cancer therapy.
Myocardial ischemia‐reperfusion injury (MIRI) is a leading cause of complications and high mortality associated with acute myocardial infarction. Injectable hydrogel emerges as a promising biomaterial for myocardial repair due to their ability to mimic the mechanical and electrophysiological properties of heart tissue. In this study, an injectable conductive hydrogel is developed that responds to the weakly acidic microenvironment of ischemic injury, enabling the intelligent release of metformin and exosomes to enhance cardiac repair following MIRI. This multifunctional hydrogel demonstrates self‐healing properties, shear‐thinning injectability, electrical conductivity, and an elastic modulus comparable to natural myocardium, alongside excellent biocompatibility. At the cellular level, the hydrogel system exhibits significant antioxidant, anti‐apoptotic, improvement of electrophysiological characteristics, mitochondrial protection and angiogenic effects, with transcriptome sequencing revealing the effective activation of the PI3K/AKT, VEGF, and AMPK signaling pathways. In vivo studies further confirm that the hydrogel treatment reduces infarct size, cardiac fibrosis and incidence of arrhythmia, while improving ventricular ejection fraction and facilitating the restoration of cardiac function after MIRI. In conclusion, an injectable pH‐responsive conductive hydrogel is presented that enables the intelligent delivery of metformin and exosomes, offering a promising and novel therapeutic approach for enhancing cardiac repair and treating MIRI.