Imaging Agents Research Articles

Understanding Bacterial Resistance to Heavy Metals and Nanoparticles: Mechanisms, Implications, and Challenges.

Antimicrobial resistance is a global health problem as it contributes to high mortality rates in several infectious diseases. To address this issue, engineered nanoparticles/nano-formulations of antibiotics have emerged as a promising strategy. Nanoparticles are typically defined as materials with dimensions up to 100nm and are made of different materials such as inorganic particles, lipids, polymers, etc. They are widely dispersed in the environment through various consumer products, and their clinical applications are diverse, ranging from contrast agents in imaging to carriers for gene and drug delivery. Nanoparticles can also act as antimicrobial agents either on their own or in combination with traditional antibiotics to produce synergistic effects, earning them the label of "next-generation therapeutics." They have also shown great effectiveness against multidrug-resistant pathogens responsible for nosocomial infections. However, overexposure or prolonged exposure to sublethal doses of nanoparticles can promote the development of resistance in human pathogens. The resistance can arise from various factors such as genetic mutation, horizontal gene transfer, production of reactive oxygen species, changes in the outer membrane of bacteria, efflux-induced resistance, cross-resistance from intrinsic antibiotic resistance determinants, plasmid-mediated resistance, and many more. Continuous exposure to nanoparticles can also transform an antibiotic-susceptible bacterial pathogen into multidrug resistance. Considering all these, the current review focuses on the mode of action of different heavy metals and nanoparticles and possible mechanisms through which bacteria attain resistance towards these heavy metals and nanoparticles.

A comparison of routine [68Ga]Ga-PSMA-11 preparation using Locametz and Illuccix kits

BackgroundApproval of Locametz and Illuccix kits for the manufacture of [68Ga]Ga-PSMA-11 (gallium Ga68 gozetotide), a PET imaging agent for prostate cancer, as well as the corresponding therapeutic ([177Lu]Lu-PSMA-617 Pluvicto), has led to a rapid increase in demand for [68Ga]Ga-PSMA-11 PET imaging. Radiopharmaceutical manufacturers, using 68Ge/68Ga generators, may decide to adopt Locametz and/or Illuccix kits, which requires a comparison to select the most suitable kit for day-to-day use. The objective of this article is to compare both kits and provide guidance for selecting one for routine use, as well as evaluate labeling consistency of both kits during routine production. Additionally, we report our experience during 1.5 years of daily [68Ga]Ga-PSMA-11 production at our facility using both kits.ResultsLocametz (n = 181) and Illuccix (n = 256) kits were prepared using non-silicone coated and silicone-coated needles with 68Ga activities ranging from 0.53 to 3.16 GBq, with a failure rate of 1 in 128 runs for both kits. With Locametz, a 3.7 GBq generator and 10-min incubation at room temperature gave doses that passed quality control (QC) testing. Use of non-silicone coated needles in the process led to solution discoloration, and QC failure. Additionally, lack of vial inversion led to inconsistent labeling, which improved with subsequent vial agitation. For Illuccix, addition of the acetate buffer to the precursor vial prior to adding the [68Ga]GaCl3 simplifies the workflow. The maximum tolerated activity was 1.85 GBq. Lack of vial inversion led to failures, which were rectified by agitating the vial to properly incorporate the acetate solution with the generator eluate.ConclusionsBoth kits benefited from using a syringe pump to elute the 68Ge/68Ga generator, vial agitation, and longer length/smaller bore silicone coated needles. Both kits have similar workflows, comparable QC outcomes, and result in equivalent clinical images. Thus, the decision between kits will ultimately be determined by production preferences. Since radiopharmacies have an established “kit-based” workflow, Locametz kits with higher allowed activities and longer shelf-life may offer benefits. Conversely, more traditional PET manufacturing facilities might benefit from using Illuccix kits due to compatibility with cyclotron-produced [68Ga]GaCl3 allowing for kit batching. Ultimately, the commercial availability of 2 approved kits for production of [68Ga]Ga-PSMA-11 PET has facilitated ready access to this important new imaging agent.

Insights into Cancer Cell Imaging Probes Based on Chalcone Scaffolds: Theoretical and Experimental Perspectives.

The research article details the synthesis of chalcone-chromone-based scaffolds via multicomponent reactions. These compounds were characterized using conventional spectroscopic methods, including NMR (1H and 13C), FT-IR, and HR-MS. Among the synthesized scaffolds, AZBNPy stood out, exhibiting exceptional DNA and protein targeting capabilities with superior binding parameters. Molecular docking studies indicated that AZBNPy has potential as a potent anticancer agent and a probe for cancer cell imaging. The findings showed that AZBNPy effectively inhibited cell proliferation and induced cell death by targeting HER-2, PARP-2, and HFR in MCF-7 cells. Additionally, in vitro fluorescence imaging studies confirmed AZBNPy's specificity for cancer cell receptors, displaying strong fluorescence in human breast cancer tissues. The clinical application of AZBNPy as an optical imaging agent holds significant promise in aiding surgeons with the precise identification and removal of cancerous tissues, potentially improving patient outcomes and survival rates.

Review of Clinically Assessed Molecular Fluorophores for Intraoperative Image Guided Surgery

The term “fluorescence” was first proposed nearly two centuries ago, yet its application in clinical medicine has a relatively brief history coming to the fore in the past decade. Nowadays, as fluorescence is gradually expanding into more medical applications, fluorescence image-guided surgery has become the new arena for this technology. It allows surgical teams to real-time visualize target tissues or anatomies intraoperatively to increase the precision of resection or preserve vital structures during open or laparoscopic surgeries. In this review, we introduce the concept of near-infrared fluorescence guided surgery, discuss the recent and ongoing clinical trials of molecular fluorophores (indocyanine green, 5-aminolevulinic acid, methylene blue, IR-dye 800CW, pafolacianine) and their surgical goals, highlight key chemical and medical factors for imaging agent optimization, deliberate challenges and potential advantages, and propose a framework for integrating this technology into routine surgical care in the near future. The notable clinical achievements of these fluorophores over the past decade strongly indicates that the future of fluorescence in surgery is bright with many more patient benefits to come.

An Upgraded Solid-Phase Assembly of Chelators (DOTA and NOTA) Enabled Bacterial Uptake Studies of Radiolabeled Peptide.

Among popular radio metal chelators, DOTA and NOTA have been remarkably considered in radionuclide therapy and imaging studies due to several advantages in pharmacology. Here, we developed a practical and general method for assembling DOTA and NOTA in the solid phase peptide (pseudo-dilute conditions) using a wide range of solvents with easily accessible and economical feedstocks, which mitigated unprecedented challenges associated with previously reported methods. This upgraded approach enabled an efficient installation of these two chelators on various bioactive peptide sequences. Finally, we assessed the antimicrobial activity of the DOTA- and NOTA-attached Combi peptides to B. subtilis, which was intact. The authenticity of the assembled DOTA framework was assessed by labeling 177Lu and in vitro bacterial uptake in E. coli and S. aureus. 177Lu-labeled DOTA-Combi peptide exhibited promising uptake for developing a bacterial infection imaging agent while negligible hemolysis activity even at >200 μM. This contribution will be valued for developing peptide radiopharmaceuticals with operational simplicity and economic approaches.

Imaging NRF2 activation in non-small cell lung cancer with positron emission tomography

Mutations in the NRF2-KEAP1 pathway are common in non-small cell lung cancer (NSCLC) and confer broad-spectrum therapeutic resistance, leading to poor outcomes. Currently, there is no means to non-invasively identify NRF2 activation in living subjects. Here, we show that positron emission tomography imaging with the system xc− radiotracer, [18F]FSPG, provides a sensitive and specific marker of NRF2 activation in orthotopic, patient-derived, and genetically engineered mouse models of NSCLC. We found a NRF2-related gene expression signature in a large cohort of NSCLC patients, suggesting an opportunity to preselect patients prior to [18F]FSPG imaging. Furthermore, we reveal that system xc− is a metabolic vulnerability that can be therapeutically targeted with an antibody-drug conjugate for sustained tumour growth suppression. Overall, our results establish [18F]FSPG as a predictive marker of therapy resistance in NSCLC and provide the basis for the clinical evaluation of both imaging and therapeutic agents that target this important antioxidant pathway.

Fluorescent imaging agents for mapping temperature field and capillary flow on the surface of volatile solvent

AbstractThe understanding of thermocapillary convection is important in both fundamental and industrial aspects. However, efficient tools that can provide dynamic details of the convective flows are still lacking. Here, we discovered a unique phenomenon of photoinduced fluorogenic shift of HDPI derivatives in chloroform and utilized this trait to map the temperature field and capillary flow on the surface of or inside volatile chloroform with a high spatial resolution and a long observation window. By inducing a proper co‐imaging agent that enhanced the fluorescence contrast via generating more distinguishable chromaticity, the fluorescence‐based method exhibited further enhanced imaging resolution and elongated observation time, facilitating the continuous monitoring of temperature field and capillary flow. This work presents a powerful tool to study the behaviors of fluid (thermo‐)dynamics.

Preclinical Evaluation of [124I]-Sotorasib for the Imaging of Kirsten Rat Sarcoma G12C Mutant Tumors.

Kirsten rat sarcoma (KRAS) is a frequently mutated oncogene responsible for several oncogenic KRAS variants and for driving tumor proliferation. Some nonsmall cell lung cancer (NSCLC) tumors exhibit KRAS G12C mutations, which can be targeted for inhibition using covalent and more recently noncovalent inhibitors. Sotorasib was the first FDA-approved G12C inhibitor that has shown efficacy in lung cancer patients, but with mixed responses. The lack of efficacy can be attributed to tumor heterogeneity (lack of G12C mutations) and/or inefficient delivery. Targeted KRAS G12C imaging has potential to identify NSCLC lesions with the targeted mutation and elucidate the oncogene's role in driving tumor growth and correlating responses to treatment. Toward this goal, we have developed a sotorasib-based molecular agent for PET imaging and tested its efficacy in targeting tumor lesions with KRAS G12C mutations. Here, we describe the synthesis, in vitro and in vivo evaluation of an [124I]I-Sotorasib analog in targeting G12C mutant tumor lesions using PET imaging.

Current Advances in Viral Nanoparticles for Biomedicine.

Viral nanoparticles (VNPs) have emerged as crucial tools in the field of biomedicine. Leveraging their biological and physicochemical properties, VNPs exhibit significant advantages in the prevention, diagnosis, and treatment of human diseases. Through techniques such as chemical bioconjugation, infusion, genetic engineering, and encapsulation, these VNPs have been endowed with multifunctional capabilities, including the display of functional peptides or proteins, encapsulation of therapeutic drugs or inorganic particles, integration with imaging agents, and conjugation with bioactive molecules. This review provides an in-depth analysis of VNPs in biomedicine, elucidating their diverse types, distinctive features, production methods, and complex design principles behind multifunctional VNPs. It highlights recent innovative research and various applications, covering their roles in imaging, drug delivery, therapeutics, gene delivery, vaccines, immunotherapy, and tissue regeneration. Additionally, the review provides an assessment of their safety and biocompatibility and discusses challenges and future opportunities in the field, underscoring the vast potential and evolving nature of VNP research.

Photoacoustic Imaging of pH-Sensitive Optical Sensors in Biological Tissues

Photoacoustic imaging is an emerging biomedical imaging technique that enables non-invasive visualization of the optical absorption properties of biological tissues in vivo. Although numerous studies have used contrast agents to achieve high-contrast imaging in deep tissues, targeting specific areas remains a challenge when using agents that are continuously activated. Recent research has focused on developing triggered contrast agents that are selectively activated in target areas. This review delves into the use of pH-triggered contrast agents in photoacoustic imaging, which take advantage of the lower pH of the tumor microenvironment compared to normal tissues. The paper discusses the mechanisms of pH-triggered contrast agents that contribute to improving depth and contrast in photoacoustic tumor imaging. In addition, the integration of functionalities, such as photothermal therapy and drug delivery monitoring, into these agents demonstrates significant potential for biomedical applications.

Preclinical Study of a Dual-Target Molecular Probe Labeled with 68Ga Targeting SSTR2 and FAP

Objective: Currently, 68Ga-labeled somatostatin analogs (SSAs) are the most commonly used imaging agents for patients with neuroendocrine tumors (NETs) in clinical practice, demonstrating good results in tumor diagnosis. For applications in peptide receptor radionuclide therapy (PRRT), targeted drugs should have high tumor uptake and prolonged tumor retention time. To enhance the uptake and retention of tracers in NETs, our goal is to design a 68Ga-labeled heterodimer for optimizing pharmacokinetics and assess whether this form is more efficacious than its monomeric equivalents. Methods: Using the somatostatin analog TATE and quinoline-based compound FAPI-46 as raw materials, we designed and synthesized 68Ga-labeled TATE-46. The labeling efficiency and stability were verified by Radio-HPLC. The receptor binding properties and tumor targeting were examined both in vitro and in vivo by using NCI-H727 (SSTR2/FAP, positive) and Mc38 (SSTR2/FAP, negative) cell lines and tumor-bearing mouse models. Preclinical evaluation was performed through cell uptake, pharmacokinetics, Micro PET, and biodistribution studies, and the results were compared with [68Ga]Ga-DOTA-TATE and [68Ga]Ga -FAPI-46. Immunohistochemistry and HE staining were performed on tumor tissues from tumor-bearing mice for further validation. Results: [68Ga]Ga-TATE-46 showed comparable SSTR2 and FAP targeting ability to monomeric TATE and FAPI-46 in cell uptake and PET imaging studies. [68Ga]Ga-TATE-46 exhibited significantly higher uptake in NCI-H727 (SSTR2/FAP, positive) tumors compared to [68Ga]Ga-DOTA-TATE (p < 0.001) and [68Ga]Ga-FAPI-46 (p < 0.001). No increased uptake of [68Ga]Ga-TATE-46 was observed in MC38 tumors (SSTR2/FAP, negative). Additionally, excess DOTA-TATE and/or unlabeled FAPI-46 significantly blocked the uptake of [68Ga]Ga-TATE-46 in NCI-H727 tumors (p < 0.001), confirming its dual-receptor targeting characteristics. The ex vivo biodistribution, immunofluorescence and immunohistochemistry results were in line with the in vivo imaging findings. Conclusion: Compared with 68Ga-labeled FAPI-46 and DOTA-TATE mono-specific tracers, the dual-target tracer [68Ga]Ga-TATE-46 improves tumor uptake, extends tumor retention, and enhances pharmacokinetics. It is an effective probe for non-invasive detection of tumors expressing FAP and SSTR2, and it is worth further studying its application in the expression of sstr2 and FAP-related tumors.

In vivo scanning laser fundus and high-resolution OCT imaging of retinal ganglion cell injury in a non-human primate model with an activatable fluorescent-labeled TAT peptide probe.

The optical imaging agent TcapQ488 has enabled imaging of retinal ganglion cell (RGC) injury in vivo in rodents and has potential as an effective diagnostic probe for early detection and intervention monitoring in glaucoma patients. In the present study, we investigated TcapQ488 in non-human primates (NHPs) to identify labeling efficacy and early signals of injured RGC, to determine species-dependent changes in RGC probe uptake and clearance, and to determine dose-limiting toxicities. Doses of 3, 6, and 12 nmol of TcapQ488 were delivered intravitreally to normal healthy NHP eyes and eyes that had undergone hemiretinal endodiathermy axotomy (HEA) in the inferior retina. Post-injection fundus fluorescence imaging using a Spectralis imaging platform (Heidelberg Engineering) documented TcapQ488 activation in RGC cell bodies. Optical coherence tomography (OCT), slit-lamp examinations, intraocular pressure measurements, and visual electrophysiology testing were performed to monitor probe tolerability. For comparison, a negative control, non-cleavable, non-quenched probe (dTcap488, 6 nmol), was delivered intravitreally to a normal healthy eye. In normal healthy eyes, intravitreal injection of 3 nmol of TcapQ488 was well-tolerated, while 12 nmol of TcapQ488 to the healthy eye caused extensive probe activation in the ganglion cell layer (GCL) and eventual retinal nerve fiber layer thinning. In HEA eyes, the HEA procedure followed by intravitreal TcapQ488 (3 nmol) injection resulted in probe activation within cell bodies in the GCL, confined to the HEA-treated inferior retina, indicating cell injury and slow axonal transport in the GCL. However, in contrast to rodents, a vitreal haze that lasted 2-12 weeks obscured rapid high-resolution imaging of the fundus. By contrast, intravitreal TcapQ488 injection prior to the HEA procedure led to minimal probe labeling in the GCL. The results of the dTcap488 control experiments indicated that fast axonal transport carried the probe out of the retina after cell body uptake. No evidence of pan-retinal toxicity or loss of retino-cortical function was detected in any of the three NHPs tested. Overall, these data provide evidence of TcapQ488 activation, without toxicity, in NHP HEA eyes that had been intravitreally injected with 3 nmol of the probe. Compared to rodents, unexpectedly rapid axonal transport in the NHPs reduced the capacity to visualize RGC cell bodies and axons through the backdrop of an intravitreal haze. Nonetheless, although intravitreal clearance rates did not scale to NHPs, HEA-induced reductions in axonal transport enhanced probe visualization in the cell body.

Evaluating the diagnostic value of 18F-FAPI-04 PET/CT in various malignant tumors: a head-to-head comparison with 18F-FDG PET/CT.

This study aims to evaluate the diagnostic efficacy of 18F-fibroblast activation protein inhibitor-04 (18F-FAPI-04) PET/CT for various malignant tumors and compare it head-to-head with 18F-FDG PET/CT. This single-center, prospective study continuously recruited patients with suspected or confirmed malignant tumors for concurrent 18F-FDG and 18F-FAPI-04 PET/CT scans from April 2022 to October 2023. The pathological diagnosis or clinical follow-up served as the reference standard. The Z-test for two proportions was used to compare the sensitivity, specificity, and accuracy of tumor diagnosis between the two imaging agents. Wilcoxon signed-rank tests were employed to compare the uptake of the two radiotracers and the tumor-to-background ratio (TBR) differences in tumors. The study involved 15 types of tumors and included 88 patients, comprising 53 males and 39 females, with an average age of 57.7 ± 10.8 years. In patient-based analysis, 18F-FAPI-04 PET/CT demonstrated higher diagnostic accuracy than 18F-FDG PET/CT for both initial staging and restaging patients (77.4% vs 56.6%, p = 0.0389; 94.3% vs 54.3%, p < 0.001), prompting treatment plan adjustments in 17% of restaged patients. The lesion-based analysis revealed comparable diagnostic accuracy of 18F-FAPI-04 PET/CT and 18F-FDG PET/CT for primary tumors (78.9% vs 75.4%, p = 0.8234), while showing superior accuracy for residual/recurrent tumors, lymph node metastases, and distant metastases compared to 18F-FDG PET/CT (100.0% vs 50.0%, p = 0.002; 98.8% vs 86.0%, p < 0.001; 98.3% vs 79.3%, p < 0.001). 18F-FAPI-04 PET/CT exhibits higher uptake and TBR in most tumors demonstrating superior diagnostic efficacy for primary lesions, residual/recurrent disease, and metastases compared to 18F-FDG PET/CT, particularly beneficial for restaging post-treatment patients.

Molecular Engineering of Ultrabright Biomimetic NanoGhost for Site-Selective Tumor Imaging and Biodistribution.

Optically active ultrabright imaging agents are shown to delineate tumor location with deep tissue visualization in pre noclinical tumor models. NanoGhosts (NGs) particles are reconstructed from the cell membrane and integrated with organic fluorophores to attain ultra-brightness for solid tumor imaging. Moreover, the integration of amphiphilic and lipophilic molecules reveals structural characteristics of NGs (≈70nm), which also alter their brightness. Upon intravenous administration (10 mgkg-1 single dose), these ultrabright NGs (778 MESF) enable the high-resolution of tumor site and real-time tracking of vital organs with high-contrast fluorescence signals. Engineered biomimetic NGs demonstrates better resolution and tissue penetration as compared to the clinically approved indocyanine green (ICG). High precision in tumor detection (0.5h) and strong tumor retention (24h which is further up to 30th day) without affecting healthy tissues ensure the future scope of NGs in early-stage cancer imaging. These findings suggest that these NGs mimic the biological characteristics of native cells, enabling them to evade immune clearance and target the solid tumor naturally.

An ACE2 PET imaging agent derived from 18F/Cl exchange of MLN-4760 under phase transfer catalysis

BackgroundAngiotensin-converting enzyme-2 (ACE2) acts as a key regulatory molecule and important therapeutic target in the pathological remodeling of numerous organs and diseases. In this study, a rapid, simple, and efficient synthetic route with a catalytic, 18F-for-Cl (18F/Cl) exchange scheme was designed for the preparation of 18F-labeled MLN-4760, and its targeting ability was investigated in a humanized ACE2 mouse model.ResultsA novel 18F-labeled MLN-4760 radioligand, abbreviated as 18F-MLN-4760, was successfully synthesized by the 18F/Cl exchange-labeling, and was purified by SepPak C18 columns with a radiochemical yield of 30% and a radiochemical purity of 29.89%. Target distribution of 18F-MLN-4760 in several organs with high ACE2 expression was observed by PET imaging with good stability over 120 min. The biodistribution data showed that the uptake of 18F-MLN-4760 in ACE2-overexpressing organs and tissues was highly specific, and immunohistochemistry confirmed the same results of ACE2 expression and biodistribution in the major organs (heart, liver, lungs, and kidneys). There was a good correlation between the uptake in the organs with high ACE2 expression and ACE2 expression levels (r = 0.935).Conclusion18F-MLN-4760 was successfully synthesized via 18F/Cl exchange under phase transfer catalysis, and served as a potential probe for ACE2-targeted PET imaging.

Theranostic and Combined Approaches Exploiting Multifunctional Gold Nanoclusters in Tumoral Ecosystems: A Paradigm Shift in Precision Oncology.

Malignant tumors pose a significant threat to human life and well-being because of their rising occurrence and size. The current treatment methods and diagnostic techniques employed in clinical practice are inadequate for effectively treating tumors. Fluorescence, photothermal effects, radiosensitization, and biocompatibility are only a few instances of the unique photonic and physicochemical properties exhibited. Gold nanoclusters (AuNCs) are nanomaterials that possess modest dimensions, typically measuring approximately 3 nm, and are composed of a limited number of particles. AuNCs have three primary functions in practical applications: serving as imaging agents, drug transporters, and therapeutic agents. This article discusses nanosystems. The text emphasizes the promise of AuNCs for tumor theranostic and combination treatment while also acknowledging any existing limitations. Lastly, it is anticipated that the information presented here will serve as a valuable tool for researchers in this sector, resulting in novel perspectives and, ultimately, a wider adoption of AuNCs in pharmaceuticals. This study focuses on the expansion of diagnostic applications in cancer therapy by utilizing AuNC-based devices, made possible by the use of dynamic or passive tumor targeting techniques. The utilization of AuNCs has been thoroughly investigated for their prospective applicability as light-activated and radiation agents. Furthermore, they have been investigated as nanocarriers for transporting anticancer drugs. The medications can either bind to the closure receptor or be linked to the AuNCs through various techniques, showcasing their extensive potential for therapeutic applications.

Synthesis and Relaxivity study of amino acid-branched radical dendrimers as MRI contrast agents for potential brain tumor imaging.

This study introduces a series of water-soluble radical dendrimers (G0 to G5) as promising magnetic resonance imaging (MRI) contrast agents that could potentially address clinical safety concerns associated with current gadolinium-based contrast agents. By using a simplified synthetic approach based on a cyclotriphosphazene core and lysine-derived branching units, we successfully developed a G5 dendrimer containing up to 192 units of 2,2,6,6-Tetramethylpiperidinyloxy (TEMPO) radical. This synthesis offers advantages including ease of preparation, purification, and tunable water solubility through the incorporation of glutamic acid anion residues. Comprehensive characterization using 1H NMR, FT-IR, and SEC-HPLC confirmed the dendrimers' structures and purity. Electron paramagnetic resonance (EPR) spectroscopy revealed that TEMPO groups in higher generation dendrimers exhibited decreased mobility and stronger spin exchange in their local environments. In vitro MRI showed that relaxivity (r1) increased with higher dendrimer generations, with G5 exhibiting an exceptionally high r1 of over 24 mM-1s-1. Molecular dynamics simulations provided crucial insights into structure-property relationships, revealing the importance of water accessibility to TEMPO groups for enhancing relaxivity. Vero cell viability assay demonstrated G3 and G3.5 have good biocompatibility. In vivo MRI experiments in mice demonstrated that G3.5 was excreted through the kidneys and selectively accumulated in glioblastoma tumors. STATEMENT OF SIGNIFICANCE: This study explores a class of MRI contrast agents based on organic radical dendrimers as a potential alternative to gadolinium-based agents. We present a simplified synthesis method for water-soluble dendrimers containing up to 192 TEMPO radical units-the highest number achieved to date for this class of compounds-resulting in record-high relaxivity values. Our approach offers easier preparation, purification, and tunable water solubility, representing an improvement over existing methods. Through combined experimental and computational studies, we provide insights into the structure-property relationships governing relaxivity. In vivo experiments demonstrate the dendrimers' potential for glioblastoma imaging, with predominantly renal excretion. This work represents a step towards developing metal-free MRI contrast agents with promising relaxivity and biocompatibility, potentially opening new avenues for diagnostic imaging research.

Cluster Missile‐Inspired Dynamic Nanocomposite Hydrogel Precisely Mediates Robust Locoregional Tumor Theranostics

AbstractLocoregional injectable tumoral theranostic nanocomposite hydrogels have shown great potential for clinical transformation, owing to their integration of the advantageous features of both systems, whilst simultaneously minimizing their drawbacks. However, how the nanomedicines efficiently escape from hydrogel and circumvent the intrinsically conflicting attributes between tumor penetration and accumulation directly determines the theranostic efficiency. Herein, a cluster missile‐inspired dynamic nanocomposite hydrogel synthesized via Schiff base reaction between crosslinked synergistic size‐changeable nano‐prodrugs (NPs) and glutaraldehyde (GA) is successfully developed. The hydrogel, analogous to a cluster missile, can efficiently release NPs with an initial size of 25.3 nm for deep tumor distribution and cellular internalization by responding to the tumoral extracellular pH, while precisely directing their exceptionally high cellular accumulation and highly selective drug release in response to the tumoral intracellular pH/glutathione (GSH), thereby achieving robust locoregional chemotherapy. Furthermore, platinum heavy metals within NPs confer upon the hydrogel an ability to spatiotemporally monitor dynamic changes in both itself and tumor tissues without necessitating additional conventional imaging agents. Thus, such a cluster missile‐inspired dynamic nanocomposite hydrogel paves the way toward clinical use for precise locoregional tumor theranostics.

Recent Advances in Pharmaceutical Design: Unleashing the Potential of Novel Therapeutics.

Pharmaceutical design has made significant advancements in recent years, leading to the development of novel therapeutics with unprecedented efficacy and safety profiles. This review highlights the potential of these innovations to revolutionize healthcare and improve patient outcomes. The application of cutting-edge technologies like artificial intelligence, machine learning, and data mining in drug discovery and design has made it easier to find potential drug candidates. Combining big data and omics has led to the discovery of new therapeutic targets and personalized medicine strategies. Nanoparticles, liposomes, and microneedles are examples of advanced drug delivery systems that allow precise control over drug release, better bioavailability, and targeted delivery to specific tissues or cells. This improves the effectiveness of the treatment while reducing side effects. Stimuli-responsive materials and smart drug delivery systems enable drugs to be released on demand when specific internal or external signals are sent. Biologics and gene therapies are promising approaches in pharmaceutical design, offering high specificity and potency for treating various diseases like cancer, autoimmune disorders, and infectious diseases. Gene therapies hold tremendous potential for correcting genetic abnormalities, with recent breakthroughs demonstrating successful outcomes in inherited disorders and certain types of cancer. Advancements in nanotechnology and nanomedicine have paved the way for innovative diagnostic tools and therapeutics, such as nanoparticle-based imaging agents, targeted drug delivery systems, gene editing technologies, and regenerative medicine strategies. Finally, the review emphasizes the importance of regulatory considerations, ethical challenges, and future directions in pharmaceutical design. Regulatory agencies are adapting to the rapid advancements in the field, ensuring the safety and efficacy of novel therapeutics while fostering innovation. Ethical considerations regarding the use of emerging technologies, patient privacy, and access to advanced therapies also require careful attention.

Nanoparticle-enhanced near-infrared fluorescence probes as a new frontier in cancer imaging

Recent advancements in nanotechnology have significantly enhanced the development of near-infrared fluorescence (NIRF) probes, positioning them as powerful tools in cancer imaging. This paper explores the unique advantages of nanoparticles incorporating NIR dyes, such as indocyanine green (ICG) and DiR, which exhibit deep tissue penetration and minimal background autofluorescence. The enhanced permeability and retention (EPR) effect facilitates selective accumulation in tumor tissues, enabling sophisticated imaging and precision-targeted drug delivery systems. This review highlights the remarkable potential of NIRF imaging techniques in molecular diagnostics, emphasizing their ability to differentiate malignant tissues at a molecular level. Additionally, we discuss various NIRF dye classifications, including cyanine and BODIPY-based probes, along with the development of multifunctional agents that enhance imaging specificity and therapeutic effectiveness. The integration of advanced targeting capabilities, including the use of antibodies and small molecules, further improves the precision of these imaging agents. While challenges remain regarding the pharmacokinetics and potential toxicity of nanoparticle-based probes, their capacity for real-time tumor tracking and the promise of multimodal imaging approaches underscore their transformative role in cancer diagnostics and treatment. By advancing the field of theranostics, nanoparticle-enhanced NIRF probes pave the way for personalized medicine and improved patient outcomes in oncology.