Latest ArticlesNuclear medicine imaging plays a critical role in early diagnosis, treatment planning, and monitoring by enabling real-time, non-invasive visualization of molecular processes. Conventional radiotracers, such as [18F]F-FDG, often suffer from limited specificity and unfavorable pharmacokinetics. Nanobodies, with their small size, high affinity, deep tissue penetration, and low immunogenicity, have emerged as valuable tools for molecular imaging. Nanobody-based radiotracers have shown promise across oncology, neurology, and immune-related diseases, supporting precision diagnostics and individualized treatment monitoring. However, challenges such as renal retention and short plasma half-life still hinder clinical translation. In this review, we present the structural and functional advantages of nanobodies and summarize the key advances, challenges, and future prospects of nanobody-based radiopharmaceuticals in nuclear medicine imaging.
Phenanthridine-based luminogens are known for their exceptional opto-electronic properties. They have been used in fluorescent materials as well as in biological fields. However, traditional methods for constructing the phenanthridine scaffold typically require pre-functionalized starting materials, photosensitizers or noble transition metals, which will complicate the synthesis and increase the cost. In this study, we introduce an efficient and metal-free approach to synthesize the phenanthridine derivates from free amines under visible-light irradiation. The phenanthridine ring is formed through a carbon insertion π-extension strategy. Significantly, rational design of the leaving group for the carbon-insertion reactions plays a crucial role. We successfully synthesized phenanthridine-based luminogens (DPA-Phen, MeO-DPA-Phen, and DMA-DPA-Phen). These luminogens display robust aggregation-induced emission (AIE) characteristics. Notably, they selectively localize within the lipid droplets (LDs) of tumor cells, demonstrating the potential of phenanthridine-based frameworks as viable LDs-selective fluorescent probes.
Near-infrared Ⅱ (NIR-Ⅱ) absorbing dye have garnered significant attention for deep-tissue tumor phototherapy and photoacoustic (PA) imaging. However, NIR-Ⅱ dyes often suffer from poor photostability due to extensive conjugated systems, and J-aggregation type typically exhibit narrow absorption spectra, posing significant challenges in matching laser wavelengths. In this work, we propose a mechanism where charge transfer (CT)-type J aggregation, driven by enhanced intramolecular charge transfer, enables the broad NIR-Ⅱ absorption peak and high photostability. The resulting dyes exhibit strong NIR-Ⅱ absorption, low dark toxicity and high phototoxicity as well as improved biocompatibility. Upon 1064 nm excitation, BDP2-NPs achieve a photothermal conversion efficiency of 34.2% and a maximum temperature of 47 ℃, indicating moderate photothermal performance. In addition, PA imaging was assessed by different laser wavelength. This study underscores the potential of aza-boron-dipyrromethene (aza-BODIPY)-based dyes for developing advanced NIR-Ⅱ agents in photothermal therapy and PA imaging.
The overuse and improper disposal of tetracyclines raise significant environmental and public health concerns due to their persistent ecotoxicological effects. However, there is still a lack of simple, readily available, and effective method for simultaneously detecting multiple tetracyclines. Herein, we present a simple fluorescent sensor array for the detection and identification of multiple tetracyclines (including tetracycline, oxytetracycline, chlortetracycline, and doxycycline) based on host-guest recognitions between albumin (host) and tetracycline (guest). Upon entering the hydrophobic cavity of albumin, tetracycline exhibits a significant enhancement in its intrinsic fluorescence. The differential binding affinity of two albumins to four tetracyclines resulted in different fluorescent responses, creating distinct fluorescence patterns for each tetracycline. With the assistance of machine learning technique, including linear discriminant analysis (LDA) and hierarchical cluster analysis (HCA), this sensor array demonstrated the significant discrimination and classification capabilities for four common tetracyclines and their mixtures with 100% accuracy. Additionally, the array has been successfully applied to differentiate tetracyclines in real food samples. The spiked antibiotics in water sample were determined with a satisfactory recovery of 96.33%–106.5%. This work offers a simple but promising method for differentiating tetracycline antibiotics and presents a versatile strategy for sensor array design.
Osteosarcoma (OS) is the most common primary bone malignancy. However, treatment remains challenging due to multidrug resistance, toxic side effects from high-dose and frequent chemotherapy, and surgery-induced bone defects. Herein, we report a double-sensitizing chemotherapeutic hydrogel for efficient OS treatment and bone regeneration, which is constructed by loading doxorubicin hydrochloride (DOX) and icaritin (ICT) into Pluronic F127 (F127) and Pluronic F68 (F68) hydrogel matrix (DOX/ICT-gel). Both ICT and Pluronics can sensitize cancer cells to DOX treatment and enhance intracellular DOX accumulation, thereby boosting the cytotoxic activity of DOX. The addition of ICT can not only downregulate the required dose of DOX and reduce the toxic side effects of DOX, but also induce osteoblast differentiation, contributing to bone regeneration. In the in-situ anti-OS study, the DOX/ICT-gel was shown to stay locally for 7 days, and effectively inhibits OS tumor growth and metastasis, providing robust anticancer efficacy with low toxicity from a single injection for long-lasting treatment. This research provides a novel dual-sensitive DOX strategy for localized OS therapy, potentially advancing the clinical management of this challenging disease.
In situ stimuli-responsive nanodevices have gained substantial attention in recent years owing to their remarkable potential to enhance tumor imaging and therapeutic effects. Herein, we formulated a pH-responsive, aptamer-functionalized DNA tetrahedral nanoplatform (ASTD) for improved visualization of survivin mRNA and chemo/gene therapy. ASTD, assembled by four single-stranded DNA, integrates pH-responsive i-motif sequences, survivin mRNA-targeted molecular beacons and AS1411 aptamers. Taking advantage of the tumor-targeting ability of AS1411 aptamer, ASTD monomers self-assemble into a multifunctional DNA polymeric tetrahedron (ASPD) on the tumor cell surface upon exposure to acidic tumor microenvironment. ASPD exhibits enhanced cellular uptake, superior survivin mRNA imaging, and efficient survivin gene silencing. Furthermore, Dox-loaded ASPD shows a significant antitumor effect, resulting in approximately 66% apoptosis of tumor cells. This study develops a dynamic DNA tetrahedral nanoplatform with diagnostic and therapeutic dual-functionalities, offering a promising strategy for advancing precise cancer theranostics.
As a technique with high sensitivity and resolution, fluorescence imaging is widely used in biomedical research, disease diagnosis and environmental monitoring, etc. Traditional fluorescence imaging mostly relies on photoexcitation paradigms, but with the deepening of multidisciplinary cross research, fluorescence excitation strategies based on multiple energy sources have gradually become an emerging frontier. These innovative strategies achieve diversified excitation of fluorescent probes by using multiple external stimuli, such as electric energy, magnetic energy, chemical energy, electromagnetic radiation, optical energy and mechanical energy, providing more flexible choices for different application scenarios, which not only broaden the application scope of fluorescence technology but also provide a new way of thinking for the design of highly efficient and tunable fluorescence systems. To track the latest advancements in fluorescence excitation techniques, this review systematically summarizes the recent multiple energy sources, focusing on their mechanisms, design principles, application prospects and challenges. By synthesizing recent research progress, this work aims to highlight emerging excitation strategies and offer valuable insights for developing next-generation fluorescent probes and broadening the technological applications of fluorescence-based systems.
Reactive oxygen species (ROS) mediated oxidative stress represents a pivotal mechanism in antimicrobial activity, but most ROS-releasing materials require external stimuli, restricting their efficacy for continuous day-night applications. In this study, we present a novel substitution strategy to synthesize Cu-doped bimetallic organic frameworks with coordinatively unsaturated metal sites (CUMS), aiming to enhance ROS-mediated antimicrobial efficacy by regulating electron transfer between Cu and valence-variable Fe sites through Cu doping. The incorporation of Cu sites effectively modifies the electronic structure of Fe sites and optimizes the energy band structure of Fe-MIL-101, facilitating the effective electron transfer between the metal sites. Furthermore, the thermal treatment promotes the formation of coordinatively unsaturated electron-rich Fe active sites, significantly enhancing the O2 adsorption and activation, which in turn boosts ROS generation. Notably, the 0.5Cu-Fe-MIL-101(CUMS) exhibits remarkable ROS generation capability, demonstrates a 99.99% antibacterial effectiveness against Escherichia coli (E. coli) within 30 min of light exposure, and maintains a 99.99% antimicrobial efficacy after 4 h in darkness, thus achieving robust day-night antimicrobial activity. Density functional theory calculations and X-ray photoelectron spectroscopy (XPS) analyses confirm that the enhanced electron transfer between Cu and Fe sites facilitates the adsorption of O2 and H2O2 on the valence-variable Fe sites, promoting the spontaneous generation of ·O2− and ·OH, which induce oxidative stress and membrane damage in bacterial cells. This study highlights the potential of strategically tailoring the electronic properties surrounding the coordinatively unsaturated metal sites in bimetallic metal organic frameworks (MOFs) for advanced antibacterial applications.
Hypertaxoids A (Hyp A, 1) and B (Hyp B, 2), two highly modified benzoyl polycyclic polyprenylated acylphloroglucinols (PPAPs) with an unprecedented carbon skeleton, were isolated from the aerial parts of Hypericum elatoides. Compounds 1 and 2 share a bicyclo[5.3.1]hendecane motif fused a 1,1-dimethylcyclohexane unit, with a taxoid-like 6/8/6 tricyclic core, while compound 1 possesses a new 6/8/6/5 tetracyclic ring system. Their structures were elucidated by a combination of nuclear magnetic resonance spectroscopy (NMR) analysis, high resolution electrospray ionization mass spectroscopy (HRESIMS), X-ray crystallography, and electronic circular dichroism (ECD) calculations. A key cation-anion progress in formation mechanism of 1 and 2 was revealed based on density functional theory (DFT) calculations. Among them, hypertaxoid B displayed selective inhibition on cell growth of human cervical cancer lines. The mechanism of action revealed that Hyp B could stabilize tubulin polymerization and disrupt the microtubule network, leading to apoptosis in C-33A cells through the mitochondria signaling pathway. Moreover, Hyp B significantly suppressed the C-33A tumor growth, brain metastasis, and angiogenesis in zebrafish xenograft models. Compound 2 represents the first tubulin polymerization-promoting natural product of PPAPs, which highlights it as a promising lead compound with a new type of skeleton for antineoplastic drug development for cervical cancer treatment.
Multivalent supramolecular assemblies not only can efficiently enhance the photophysical properties of functional molecules, but also are able to intelligently modulate the luminescence behavior. Herein, the photo-controlled reversible multicolor luminescent supramolecular assembly was constructed on agarose substrate by non-covalent interactions, which was composed of multicharged β-cyclodextrin (AMCD) with adamantane-modified spiropyrane derivative (Adam-SP) and tetraphenylethene derivatives (TPE). Firstly, the positively charged AMCD and negatively charged TPE form a binary assembly AMCD@TPE through electrostatic interaction, significantly enhancing the luminescence of TPE at 480 nm with a quantum yield (QY) jump from 0.68% to 31.24%. Moreover, the binary assembly AMCD@TPE and Adam-SP further formed a ternary assembly Adam-MC@AMCD@TPE through strong host-guest interaction, which not only achieved photo-regulated multicolor reversible fluorescence in both aqueous solution and agarose hydrogel under alternating visible light irradiation and dark treatment, but also produced adjustable luminescence changes under thermal stimulation. The ternary assembly Adam-MC@AMCD@TPE was successfully applied to photo-controlled multiple anti-counterfeiting.
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