Search Results (407)

Background/Objectives: Peptide receptor radionuclide therapy (PRRT) is an established treatment for neuroendocrine tumors (NETs), enabling targeted radiation delivery via radiolabeled peptides. Small cell lung cancer (SCLC) remains a major therapeutic challenge due to its aggressive nature and poor prognosis. Despite advances, relapse rates are high and effective therapies are limited. We previously demonstrated the diagnostic potential of the cholecystokinin-2 receptor (CCK2R)-targeting minigastrin analog [⁶⁸Ga]Ga-DOTA-MGS5 in PET/CT imaging of different NETs. Building on this, we developed and evaluated [¹⁷⁷Lu]Lu-DOTA-MGS5 as a therapeutic PRRT agent. Methods: Preclinical studies investigating the receptor-mediated cellular internalization and intracellular distribution over time in A431 cells with and without CCK2R expression were performed using the fluorescent tracer ATTO-488-MGS5. Short- and long-term cytotoxic effects of [¹⁷⁷Lu]Lu-DOTA-MGS5 were evaluated on the same cell line using trypan blue exclusion and clonogenic survival assays. CCK2R expression was assessed by immunohistochemistry in 42 SCLC tissue specimens. In addition, the first PRRT with [¹⁷⁷Lu]Lu-DOTA-MGS5 was conducted in a patient with extensive disease SCLC (ED-SCLC) after confirming CCK2R-positive uptake in [⁶⁸Ga]Ga-DOTA-MGS5 PET/CT. Results: Rapid binding and internalization into A431-CCK2R cells, with progressive accumulation in intracellular compartments, was observed for ATTO-488-MGS5. Short-term irradiation effects of [¹⁷⁷Lu]Lu-DOTA-MGS5 were comparable for 4 h and 24 h incubation and were between the effects obtained with 2 and 4 Gy of external beam radiotherapy (EBRT). Clonogenic survival of A431-CCK2R cells incubated with increasing activity of [¹⁷⁷Lu]Lu-DOTA-MGS5 decreased in a dose-dependent manner. Immunohistochemistry on SCLC specimens confirmed moderate to high CCK2R expression in 16 out of 42 SCLC samples. In the first patient with SCLC treated with four cycles of [¹⁷⁷Lu]Lu-DOTA-MGS5 with a total activity of 17.2 GBq, an improvement in clinical symptoms was observed. Conclusions: The preclinical and clinical results confirm the feasibility of [¹⁷⁷Lu]Lu-DOTA-MGS5 PRRT in patients with SCLC and support further clinical studies investigating the therapeutic value and clinical applicability of this new CCK2R-targeted theranostic approach in larger patient cohorts. Full article

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder marked by persistent memory impairment and complex molecular and cellular pathological changes in the brain. Current treatments, including acetylcholinesterase inhibitors and memantine, only help with symptoms for a short time and do not stop the disease from getting worse. This is mainly because these drugs do not reach the brain well and are quickly removed from the body. The blood–brain barrier (BBB) restricts the entry of most drugs into the central nervous system; therefore, new methods of drug delivery are needed. Nanotechnology-based drug delivery systems (NTDDS) are widely studied as a potential approach to address existing therapeutic limitations. Smart biosensing nanoparticles composed of polymers, lipids, and metals can be engineered to enhance drug stability, improve drug availability, and target specific brain regions. These smart nanoparticles can cross the BBB via receptor-mediated transcytosis and other transport routes, making them a promising option for treating AD. Additionally, multifunctional nanocarriers enable controlled drug release and offer theranostic capabilities, supporting real-time tracking of AD treatment responses to facilitate more precise and personalized interventions. Despite these advantages, challenges related to long-term safety, manufacturing scalability, and regulatory approval remain. This review discusses current AD therapies, drug-delivery strategies, recent advances in nanoparticle platforms, and prospects for translating nanomedicine into effective, disease-modifying treatments for AD. Full article

Modern medicine requires effective, continuous, and safe therapies, which largely depend on the targeted delivery and activity of the drug. This goal can be achieved by designing drug delivery systems with improved pharmacokinetic properties and enhanced drug transport to the affected tissue. Human serum albumin (HSA) is an attractive carrier for the synthesis of therapeutic nanoparticles, several of which have already been approved by the United States Food and Drug Administration (FDA). The success of Abraxane as an effective treatment for metastatic breast cancer and non-small cell lung carcinoma, the application of Optison in ultrasound imaging, and the use of Nanocoll as an agent for SPECT diagnostics in sentinel node localisation confirm the strong potential of albumin-based systems. Further benefits are expected in patients with soft tissue cancers, as LadRx is seeking FDA marketing approval for Aldoxorubicin. The future of oncology lies in theranostics, which combines a tumour-localising factor on one platform with a drug targeting cancer cells and a factor that activates the cytotoxicity of the drug after it reaches the target tissue. This article presents recent advancements in albumin-based nanoparticles for drug delivery, targeting, and imaging. It also briefly discusses methods of synthesis and surface modification of albumin nanocarriers to enable targeted delivery to pathological sites. Finally, it outlines the latest approaches in multimodal theranostic platforms, highlighting albumin’s potential to improve cancer therapy. Full article

Actinium-225 (²²⁵Ac) has emerged as a pivotal alpha-emitter in modern radiopharmaceutical therapy, offering potent cytotoxicity with the potential for precise tumour targeting. Accurate, patient-specific image-based dosimetry for ²²⁵Ac is essential to optimize therapeutic efficacy while minimizing radiation-induced toxicity. Establishing a robust dosimetry workflow is particularly challenging due to the complex decay chain, low administered activity, limited count statistics, and the indirect measurement of daughter gamma emissions. Clinical single-photon emission computed tomography/computed tomography protocols with harmonized acquisition parameters, combined with robust volume-of-interest segmentation, artificial intelligence (AI)-driven image processing, and voxel-level analysis, enable reliable time-activity curve generation and absorbed-dose calculation, while reduced mixed-model approaches improve workflow efficiency, reproducibility, and patient-centred implementation. Cadmium zinc telluride-based gamma cameras further enhance quantitative accuracy, enabling rapid whole-body imaging and precise activity measurement, supporting patient-friendly dosimetry. Complementing these advances, the cerium-134/lanthanum-134 positron emission tomography in vivo generator provides a unique theranostic platform to noninvasively monitor ²²⁵Ac progeny redistribution, evaluate alpha-decay recoil, and study tracer internalization, particularly for internalizing vectors. Together, these technological and methodological innovations establish a mechanistically informed framework for individualized ²²⁵Ac dosimetry in targeted alpha therapy, supporting optimized treatment planning and precise response assessment. Continued standardization and validation of imaging, reconstruction, and dosimetry workflows will be critical to translate these approaches into reproducible, patient-specific clinical care. Full article

Atherosclerosis remains a leading cause of cardiovascular mortality despite advances in pharmacological and interventional therapies. Current treatment approaches face limitations including systemic side effects, inadequate local drug delivery, and restenosis following vascular interventions. Gel-based technologies offer unique advantages through tunable mechanical properties, controlled degradation kinetics, high drug-loading capacity, and potential for stimuli-responsive therapeutic release. This review examines gel platforms across multiple scales and applications in atherosclerosis research and intervention. First, gel-based in vitro models are discussed. These include hydrogel matrices simulating plaque microenvironments, three-dimensional cellular culture platforms, and microfluidic organ-on-chip devices. These devices incorporate physiological flow to investigate disease mechanisms under controlled conditions. Second, therapeutic strategies are addressed through macroscopic gels for localized treatment. These encompass natural polymer-based, synthetic polymer-based, and composite formulations. Applications include stent coatings, adventitial injections, and catheter-delivered depots. Natural polymers often possess intrinsic biological activities including anti-inflammatory and immunomodulatory properties that may contribute to therapeutic effects. Third, nano- and microgels for systemic delivery are examined. These include polymer-based nanogels with stimuli-responsive drug release responding to oxidative stress, pH changes, and enzymatic activity characteristic of atherosclerotic lesions. Inorganic–organic composite nanogels incorporating paramagnetic contrast agents enable theranostic applications by combining therapy with imaging-guided treatment monitoring. Current challenges include manufacturing consistency, mechanical stability under physiological flow, long-term safety assessment, and regulatory pathway definition. Future opportunities are discussed in multi-functional integration, artificial intelligence-guided design, personalized formulations, and biomimetic approaches. Gel technologies demonstrate substantial potential to advance atherosclerosis management through improved spatial and temporal control over therapeutic interventions. Full article

Prostate cancer remains one of the most common malignancies in men worldwide, with incidence and mortality steadily increasing across diverse populations. While early detection and radical prostatectomy can achieve durable control in a subset of patients, approximately 40% of men will ultimately experience biochemical recurrence often in the absence of clinically detectable disease. Conventional imaging approaches—CT, MRI, and bone scintigraphy—have limited sensitivity for early relapses, frequently leading to delayed diagnosis and suboptimal treatment planning. The discovery of prostate-specific membrane antigen (PSMA) in 1987 and its subsequent clinical translation into positron emission tomography (PET) imaging with [⁶⁸Ga]Ga-PSMA-11 in 2012, followed by U.S. FDA approval in 2020, has transformed the landscape of prostate cancer imaging. PSMA PET has demonstrated superior accuracy over conventional imaging, as highlighted in the landmark proPSMA trial and now serves as the foundation for theranostic approaches that integrate diagnostic imaging with targeted radioligand therapy. The clinical approval of [¹⁷⁷Lu]Lu-PSMA-617 (Pluvicto^®: (lutetium Lu 177 vipivotide tetraxetan, Advanced Accelerator Applications USA, Inc., a Novartis company) has established targeted radioligand therapy as a viable option for men with metastatic castration-resistant prostate cancer, extending survival in patients with limited alternatives. Emerging strategies, including next-generation ligands with improved tumor uptake and altered clearance pathways, as well as the integration of artificial intelligence for imaging quantification, are poised to further refine patient selection, dosimetry, and treatment outcomes. This review highlights the evolution of PSMA-based imaging and therapy, discusses current clinical applications and limitations, and outlines future directions for optimizing theranostic strategies in prostate cancer care. Full article

N6-methyladenosine (m⁶A) constitutes the most prevalent nucleotide modification within eukaryotic messenger RNA (mRNA). Variations in m⁶A levels are associated with numerous human diseases and health conditions, including various forms of cancer, diabetes, neurological disorders, male infertility, and obesity. Nevertheless, the molecular mechanisms underpinning the recognition of m⁶A by different ‘reader’ proteins remain incompletely elucidated. In this study, we used phage display to identify key sequence features that methyl readers recognize in m⁶A. This study shows that m⁶A modifications affect the mRNA interactome. A peptide motif recognizing m⁶A in DRACH sequences suggests a common recognition mechanism, though proteins may use different methods to detect m⁶A in less accessible areas. The sequence of the hnRNP A1 RRM domain that aligns with the newly discovered m⁶A-binding peptide, m1p1, is crucial for the binding of m⁶A-modified RNAs, indicating a strong link between the m1p1 sequence and m⁶A recognition, which is key for recognizing m⁶A-modified, unstructured RNAs. Gaining a comprehensive understanding of the evolutionary influence of m⁶A on its reader proteins may facilitate the identification of additional m⁶A readers. These signature peptides could enhance theranostic approaches across cancers, enabling more targeted therapies. Full article

Theranostic approaches employing radioactive materials have emerged as innovative strategies that integrate molecular imaging with targeted therapy using nanosystems, thereby advancing the paradigm of precision medicine in oncology. Each year, substantial research efforts are dedicated to developing molecular probes capable of detecting early-stage tumors, with improved efficacy and reduced toxicity to the surrounding healthy tissues. Radiopharmaceuticals based on vitamins and nanoparticles are among the most promising developments in this field, as they possess a high level of specificity and low toxicity. Vitamin B9 and vitamin B12 represent notable examples, as their targeting properties exploit the overexpression of corresponding receptors in tumor cells. In this context, future directions may include the radiolabeling of nanoparticles functionalized with these vitamins using isotopes such as [⁶⁸Ga] and [¹⁷⁷Lu], thereby enabling both diagnostic imaging and therapeutic applications. Despite the encouraging preclinical evidence, many in vitro and in vivo studies employing these strategies do not sufficiently address their translational applicability to radiotheranostics. This review highlights the most promising advances in the diagnostic and therapeutic potential of vitamin and nanoparticle-based systems. It aims to critically evaluate current findings and propose hypotheses for further study in the emerging field of radiopharmaceutical theranostics. Full article

Cell-based drug delivery has emerged as a powerful strategy to improve therapeutic targeting while reducing systemic toxicity. This approach is particularly valuable for anticancer agents, which are often limited by severe side effects arising from off-target activity and non-specific distribution. By using cells as carriers, drugs can evade immune clearance, achieve prolonged circulation, and improve pharmacokinetic profiles, ultimately enhancing therapeutic efficacy. This review surveys the current landscape of cell-mediated drug delivery in oncology, emphasizing both fundamental principles and practical applications. We discuss the design and preparation of cellular carriers, examine the unique characteristics of commonly used cell types, and highlight recent technological innovations that are expanding their theranostic potential, focusing on strategies for delivery to challenging anatomical sites, with a dedicated focus on the brain. By consolidating recent advances and insights, this review aims to provide a comprehensive perspective on the promise and future directions of cell-based drug delivery for cancer therapy. Full article

Background/Objectives: Neuroblastoma (NB) is the most common extracranial solid tumor in children and accounts for 12–15% of pediatric cancer-related deaths. Current multimodal therapies lack specific cellular targets, causing systemic toxicity and drug resistance. The development of innovative tumor-targeted nanoformulations might represent a promising approach to enhance NB diagnosis and antitumor efficacy, while decreasing off targets side effects. Fibronectin extra-domain B (FN-EDB) is upregulated in the tumor microenvironment. Methods: FN-EDB expression was evaluated by immunohistochemical staining in cell line-derived and tumor patient-derived animal models of NB. A gold nanoparticle, decorated with an antibody (Ab) recognizing FN-EDB (L19-AuNP) was developed by the company Nano Flow and its tumor binding was tested by ELISA in vitro and in patient-derived xenograft (PDX) models of NB by photoacoustic imaging in vivo. Results: All animal models of NB used have been shown to express FN-EDB. L19 Ab demonstrated excellent binding specificity to FN-EDB both when used in free form and after conjugation to AuNP. Compared to the non-functionalized (no Ab L19-coupled) AuNP, which showed an increase in PDI and zeta potential over time, making them unsuitable for use in in vivo studies, L19-AuNP demonstrated good stability. In vivo, L19-AuNP specifically homed into PDX models of NB, accumulating better in tumors expressing higher levels of FN-EDB. Negligible distribution to healthy organs occurred. Conclusions: In this preliminary study, L19-AuNP was shown to be a novel diagnostic tool specifically for binding NB expressing FN-EDB, paving the way for the development of theranostic nanoformulations co-encapsulating gold moiety and standard-of-care therapy for NB. Full article

Background: Gold nanoparticles (AuNPs) are metallic nanoparticles with strong biomedical potential and have FDA approval. Their nanoscale size, optical tunability, and biocompatibility allow them to be used for tumor-targeted delivery, photothermal therapy, imaging contrast, radiosensitization, gene transfection, biosensing, personalized medicine and AI-supported healthcare solutions. These properties made AuNPs a game-changing tool in nanomedicine. Methods: Google Scholar, PubMed, Scopus and ScienceDirect were used to search the literature with keywords related to gold nanoparticles, synthesis, functionalization and advanced applications in biomedicine. The search mainly focused on studies published between 2018–2025, and older landmark papers were only included when needed to describe classical synthesis. Results: Standard AuNP synthesis and functionalization approaches were compared with advanced methods such as green synthesis, microfluidic synthesis, polymer functionalization and AI-supported synthesis optimization. AuNPs moved from traditional drug administration and basic diagnostics into multiplex imaging, targeted therapy, hybrid theranostics, spectral CT imaging, gene delivery and CRISPR-related applications. Conclusions: This review demonstrates the evolution of AuNPs in biomedicine from traditional nanoparticles to sophisticated multifunctional nanosystems. To the best of our knowledge, this is the first assessment that explicitly contrasts sophisticated AuNP techniques with conventional procedures in biomedical applications. Full article

Cancer remains a severe global health threat, with traditional therapies often plagued by limited efficacy and significant side effects. The emergence of nanotechnology, particularly metal-doped nanomaterials, offers a promising avenue for integrating diagnostic and therapeutic functions into a single platform, enabling a theranostic approach to oncology. This article explores the design and application of various metal-doped nanosystems, including gadolinium-doped selenium molybdenum nanosheets for magnetic resonance/photoacoustic dual-mode imaging and photothermal therapy, and metal-doped hollow mesoporous silica nanoparticles that leverage the tumor’s acidic microenvironment to release ions for catalytic generation of reactive oxygen species. Despite their promise, the limited enzyme-like activity of some nanozymes, insufficient endogenous hydrogen peroxide in tumors, and the tumor microenvironment’s defensive mechanisms, such as high glutathione levels, can restrict therapeutic efficacy. Looking forward, the outlook for the field is contingent upon advancing material engineering strategies. Future research should prioritize the development of intelligent, multifunctional nanoplatforms that can dynamically respond to and remodel the tumor microenvironment. Innovations in surface modification for enhanced targeting, alongside rigorous preclinical studies focused on safety and standardized manufacturing, are crucial for bridging the gap between laboratory research and clinical application, ultimately paving the way for personalized cancer medicine. Full article

Plasma cell myeloma (PCM) is classified as a blood cancer and is characterized by the abnormal proliferation of plasma cells in the bone marrow and the excessive production of monoclonal immunoglobulins, which lead to permanent damage to vital organs. Although treatment strategies have improved with the development of proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), and monoclonal antibodies (mAbs), PCM remains an incurable disease due to its molecular heterogeneity and the development of drug resistance. In this review, we discuss the biochemical and molecular foundations underlying the diagnosis and treatment of PCM, emphasizing both traditional and advanced approaches. Classical methods such as serum protein electrophoresis (SPEP), immunofixation electrophoresis (IFE), and serum free light chain (sFLC) determination are highlighted alongside their integration with highly sensitive techniques like mass spectrometry (MS) and next-generation sequencing (NGS). Special attention is given to nanotechnology-based systems, including liposomes, polymeric nanoparticles (NPs), dendrimers, and hybrid nanocapsules, which enable controlled drug release, targeted delivery, and the minimization of systemic toxicity. Increasingly, nanomaterials are being shown to greatly enhance the biodistribution and pharmacokinetics of anticancer drugs, leading to improved therapeutic effects and escaping resistance mechanisms by employing multifunctional strategies that include dual drug co-encapsulation, pH-sensitive release and theranostic applications. Furthermore, the integration of nanotechnology with immunotherapy platforms represents a paradigm shift toward precision and personalized medicine for the treatment of PCM. Overall, this review views nanotechnology as an enabling technology to improve therapeutic effectiveness, minimize toxicity and open new avenues toward next-generation smart and personalized therapeutics for the treatment of PCM. Full article

Parathyroid carcinoma (PC) is an exceedingly rare endocrine malignancy, accounting for less than 1% of all primary hyperparathyroidism (pHPT) cases. It typically presents with pronounced hypercalcemia and markedly elevated parathyroid hormone (PTH) levels. Accurate imaging plays a pivotal role in diagnosis, staging, surgical planning, and long-term surveillance, although differentiating PC from benign disease on imaging remains a significant challenge. A multimodal imaging strategy combining cervical ultrasonography (US) and nuclear medicine techniques provides high sensitivity for lesion detection. Ultrasonography with advanced detective flow imaging allows detailed anatomical assessment and evaluation of vascular patterns of the primary tumor. [^99mTc]Tc-methoxyisobutylisonitrile ([^99mTc]Tc-MIBI) scintigraphy frequently demonstrates prolonged tracer retention in PC, while [¹⁸F]fluorocholine positron emission tomography/computed tomography (PET/CT) and positron emission tomography/magnetic resonance (PET/MR) imaging have shown superior performance for detecting both primary tumors and metastatic disease due to its higher spatial resolution and higher molecular sensitivity. [¹⁸F]FDG PET serves as an adjunct modality for identifying aggressive, metabolically active lesions. Emerging radiotracers such as [¹⁸F]-fibroblast activation protein inhibitor ([¹⁸F]FAPI) and [⁶⁸Ga]Ga-trivehexin have shown potential in cases where initial imaging is inconclusive. Theranostic strategies that integrate molecular imaging with targeted radioligand therapy may transform PC management by enabling personalized treatment approaches tailored to each tumor’s biological and imaging characteristics. This review aims to evaluate available imaging modalities for PC diagnosis and provide guidance for their clinical application. Full article

Prostate cancer (PCa) remains one of the most prevalent malignancies among men worldwide and continues to pose significant therapeutic challenges, especially in its metastatic and castration-resistant forms. Over the past two decades, the treatment paradigm has evolved from monotherapy with androgen deprivation therapy (ADT) to a multifaceted approach integrating chemotherapy, androgen receptor axis-targeted therapies (ARATs), radiopharmaceuticals, and precision medicine. This review explores the molecular underpinnings of PCa, including genetic and epigenetic alterations such as BRCA1/2, TP53, and PTEN mutations, and their role in disease progression and treatment resistance. We detail the evidence supporting the integration of systemic agents like abiraterone, enzalutamide, and darolutamide into both hormone-sensitive and castration-resistant settings. Furthermore, we highlight the expanding role of radioligand therapies, including radium-223 and Lutetium-177-labeled PSMA-617 (Lu-PSMA-617), as well as the growing impact of PARP inhibitors in genomically selected patients. The emergence of theranostic strategies and next-generation sequencing has paved the way for personalized treatment algorithms, moving toward a truly precision oncology model in PCa. This comprehensive review synthesizes current therapeutic strategies, clinical trial evidence, and future directions aimed at optimizing outcomes and quality of life for patients with advanced prostate cancer. Full article