Therapeutic System Research Articles

Harnessing Folate Receptors: A Comprehensive Review on the Applications of Folate-Adorned Nanocarriers for the Management of Melanoma.

The advancement in exclusively tailored therapeutic delivery systems has escalated a great deal of interest in targeted delivery to augment therapeutic efficacy and to lessen adverse effects. The targeted delivery approach promisingly helps to surmount the unmet clinical needs of conventional therapies, including chemoresistance, limited penetration, and side effects. In the case of melanoma, various receptors were overexpressed on the tumor site, among which folate receptor (FR) targeting is considered to be a progressive approach for managing melanoma. FRs are the macromolecules of the glycosyl phosphatidylinositol-attached protein that possess globular assembly with a greater affinity toward specific ligands. So, the functional ligands can be utilized to design targeted nanocarriers (NCs) that can effectively bind to overexpressed FRs. Hence, folate-adorned NCs (FNCs) offer various benefits such as site-specific targeting, cargo protection, and minimizing toxicity. This review focuses on the insights and implications of FRs, targeting FRs, and mechanisms, challenges, and advantages of FNCs. Further, the applications of various FNCs, such as liposomes, polymeric NCs, albumin nanoparticles, inorganic NCs, liquid crystalline nanoparticles, and nanogels, have been elaborated for melanoma therapy. Likewise, the potential of FNCs in immunotherapy, photodynamic therapy, chemotherapy, gene therapy, photothermal therapy, and tumor imaging has been exhaustively discussed. Furthermore, translational hurdles and potential solutions are discussed in detail. The present review is expected to give thoughtful ideas to researchers, industry stakeholders, and formulation scientists for the efficacious development of FNCs.

Multilamellar hyaluronic acid-b-poly(lactic acid) polymersomes for pathology-responsive MRI enhancement.

This study introduces a biocompatible, stimuli-responsive imaging and therapeutic delivery system using ultrasmall iron oxide nanoparticles (USPIONs) encapsulated within the hyaluronic acid-b-poly(lactic acid) (HA-PLA) polymersome membrane, with a model protein bovine serum albumin in the core. These multilamellar vesicles exhibit enhanced T2-weighted MRI contrast, achieving a relaxivity 3-fold higher than existing agents. The polymersomes demonstrate acid- and enzyme-triggered degradation, enabling controlled release and measurable contrast changes in pathological environments. Preliminary in vivo and postmortem studies confirm their strong imaging performance, high biocompatibility, and targeted response to enzymatic, acidic microenvironments, paving the way for theranostic applications in disease diagnosis and treatment monitoring.

Cell-Targeting Bio-Catalytic Killer Protocell for High-Order Assembly Guided Cancer Cell Inhibition.

The design and construction of synthetic therapeutic protocells capable of engaging in high-order assembly with living cells represent a significant challenge in synthetic biology and bioengineering. Inspired by cell membrane receptor-ligand systems, a protocell bioreactor is developed for targeted cancer cell elimination. This is achieved by constructing orthogonal, polysaccharide-based protocells (polysaccharidosomes, P-somes) through a bottom-up approach that leverages host-guest chemistry. The protocells are assembled via electrostatically-driven self-assembly of β-cyclodextrin (β-CD)-modified amino-dextran on a sacrificial template encapsulating glucose oxidase (GOx). To enable specific cancer cell targeting and catalytic activity, cell-targeting ligands (arginylglycylaspartic acid, cRGD) and catalase-like platinum-gold nanoparticles (Pt-AuNPs) are introduced through host-guest interactions, forming a fully functional, cell-targeting, bio-catalytic killer protocell. These protocells are programmed to spatially couple the GOx/Pt-AuNP catalytic reaction cascade. In the presence of glucose and hydroxyurea, this cascade generates a localized flux of nitric oxide (NO), which is exploited for in vitro cancer cell inhibition. Overall, the results highlight the potential of integrating orthogonal and synergistic tumor inhibition mechanisms within synthetic microcompartments. This platform demonstrates promise for future therapeutic applications, especially in cancer treatment, and represents a step forward in the development of programmable protocell-based therapeutic systems.

Abstract 6492: Development of transparent compound zebrafish tumor microenvironment (TME) model system

Abstract Transgenic (Tg) zebrafish are paramount for studying the phenotypes resulting from overexpression of selected genes globally, or in a tissue-targeted fashion and growing numbers of tissue-specific promoters are becoming available to allow very precise targeting of transgene expression. In our proposed zebrafish glioblastoma experimental therapeutic model system, the first specific aim to develop the homozygous transparent compound transgenic strains from individual transparent transgenic progenies for glioblastoma tumor microenvironment (TME). Development and generation of transparent compound transgenic line Casper; Tg(mpeg1:mcherry; islet1:GFP) to study CNS resident macrophage, microglial activity and glial cell Interaction. Development and generation of transparent compound transgenic line Casper; Tg(mpeg1:mcherry; myl7:RFP; secA5:YFP) to study microglia, cardiac function, and cell death marker Annexin-5.Development and generation of transparent compound transgenic line Casper; Tg(mpeg1:mcherry; islet1:GFP; myl7:RFP; secA5:YFP) to study microglia, glial cell, cardiac function and cell death marker Annexin-5. Development and generation of transparent compound transgenic line Casper; Tg(mpeg1:mcherry;NF-kB:GFP) to study microglia, NFkB Inflammatory activity. Development and generation of transparent compound transgenic line Casper;Tg(mpeg1:mcherry; myl7:RFP; secA5:YFP; NF-kB:GFP) to study microglia, cardiac function and cell death marker Annexin-5 and NF-kB Inflammatory activity. Development and generation of transparent compound transgenic line Casper; Tg(mpeg1:mcherry; vgfr:EGFP) and Casper; Tg(mpeg1:mcherry; kdrl:EGFP) to study microglia and blood vessels and angiogenesis. Development and generation of compound transgenic line Casper; Tg(mpeg1:mcherry;fli:GFP) to study microglia, blood vessels, and vasculature. Development and generation of compound transgenic line Casper:Tg(mpx:GFP);Tg(fms:gal4); Tg(UAS:nfsB.mCherry) to study neutrophils, macrophages inflammatory process. Development and generation of compound transgenic line: Casper:Tg(VEGFR2:AcGFP x CREST3-tag RFP-2A-NTR) to study Crest trigeminal nerve and VGFR blood vessel interaction. By developing a transparent compound transgenic zebrafish model, this specific aim will lead us to explore the glioblastoma tumor microenvironment related biological process alterations and screening of new drugs to improve the diagnosis and treatment of this deadly invasive brain tumor. Citation Format: Surendra Rajpurohit, Arishia Mishra, Rohan Pasi, Shubhra Rajpurohit, Sai Nasanally, Sreeja Sappati, Keyana Williams, Timothy Pham, Ethan Clegg, Kirk Kimmerling, Vishal Arora, Balakrishna Lokeshwar. Development of transparent compound zebrafish tumor microenvironment (TME) model system [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6492.

Rehabilitation applied with virtual reality improves functional capacity in post-stroke patients. A systematic review and meta-analysis.

Rehabilitation applied with virtual reality improves functional capacity in post-stroke patients. A systematic review and meta-analysis.

Advances of Metal-Based Nanomaterials in the Prevention and Treatment of Oral Infections.

The complicated environment of the oral cavity presents significant challenges to traditional antibacterial approaches, which has driven the exploration of novel therapeutic strategies. Metal-based nanomaterials (MNMs), with diverse antibacterial mechanisms (e.g., membrane disruption, oxidative stress) and evolution from empirical to theory-guided design, exhibit immense potential. This review introduces the pioneering Hierarchical Response Strategy Framework, systematically classifying MNM therapeutic systems into three progressive levels: Primary category, comprising MNMs that exert spontaneous antibacterial effects based on inherent physicochemical properties (e.g., ion release); Secondary category, including MNMs with precisely controlled antibacterial actions by microenvironmental or stimulus-responsive mechanisms (e.g., light-induced ROS); and Tertiary category, encompassing MNMs that integrate antibacterial and regenerative functions for multidimensional therapy (e.g., remineralization). Through this framework, the authors elucidate MNMs' transition from single-function to precision-controlled, multifunctional synergy, analyze the impact of metal elements and structural design on efficacy, and summarize their applications in dental caries, endodontic infections, and periodontal disease, etc. This framework offers a novel perspective on existing research and a theoretical foundation for the rational design of next-generation precise, smart, and comprehensive anti-infective materials.

Paving the way for bacteria-based drug delivery: biohybrid microrobots emerging from microrobotics and synthetic biology.

Advances in microrobotics and synthetic biology are paving the way for innovative solutions to long-standing challenges in drug delivery. Both fields have independently worked on engineering bacteria as a therapeutic system, focusing on enhancing propulsion, cargo delivery, detection, and biocompatibility. Bacteria, with their inherent adaptability and functional versatility, serve as an ideal foundation for these efforts, enabling them to navigate complex biological environments such as the human body. This review explores the convergence of microrobotics and synthetic biology, which has catalysed the development of biohybrid bacterial microrobots that integrate the strengths of both disciplines. By incorporating external control modalities - such as light, ultrasound, and magnetic fields - these hybrid systems address the limitations of purely microrobotic or biological approaches, offering new opportunities to enhance precision and efficacy in targeted therapies. However, realising the full potential of biohybrid bacterial microrobots requires overcoming critical challenges, such as ensuring compatibility between biological and synthetic components, scaling manufacturing processes, and defining regulatory pathways tailored to living therapeutics. Addressing these hurdles through joint, interdisciplinary research efforts, can unlock the transformative possibilities of these systems in modern medicine.

Recent Advancements, Patents, and Scientific Insights into the Biomedical Soft Robots Using Nanomaterials and Nanotechnology.

This study investigates the most recent advancements in the field of biomedical soft robotics, with a primary emphasis on the integration of nanomaterials and nanotechnology. It underscores the biocompatibility, flexibility, and performance of soft robots by emphasizing critical advancements in nanomaterials, robotics, and biomedical applications. Nanomaterials can improve the biocompatibility and mechanical qualities of soft robots used in tissue engineering and regenerative medicine. Nanotechnology enables the development of flexible and elastic electronics, which may be integrated into soft robotics. This study also analyzes recent patents, offering a viewpoint on emerging technologies and their potential impact on medical diagnostics, therapeutic delivery systems, and minimally invasive procedures. The scientific developments and patents with the functioning and operating mechanisms of soft robots, as well as the problems of constructing biomedical soft robots with nanomaterials and nanotechnology, are examined in this critical study. Moreover, it also examines current advancements, patents, technological challenges, and future trends in nanomaterials and nanotechnology used in biomedical soft robotics.

Comparison of Bioelectric Signals and Their Applications in Artificial Intelligence: A Review

This review examines the role of various bioelectrical signals in conjunction with artificial intelligence (AI) and analyzes how these signals are utilized in AI applications. The applications of electroencephalography (EEG), electroretinography (ERG), electromyography (EMG), electrooculography (EOG), and electrocardiography (ECG) in diagnostic and therapeutic systems are focused on. Signal processing techniques are discussed, and relevant studies that have utilized these signals in various clinical and research settings are highlighted. Advances in signal processing and classification methodologies powered by AI have significantly improved accuracy and efficiency in medical analysis. The integration of AI algorithms with bioelectrical signal processing for real-time monitoring and diagnosis, particularly in personalized medicine, is emphasized. AI-driven approaches are shown to have the potential to enhance diagnostic precision and improve patient outcomes. However, further research is needed to optimize these models for diverse clinical environments and fully exploit the interaction between bioelectrical signals and AI technologies.

Circular RNAs perspective: exploring the direction of immunotherapy for colorectal cancer

Circular RNAs (circRNAs) are multifaceted molecules that play a pivotal role in regulating gene expression at both transcriptional and post-transcriptional levels. Their expression is highly tissue-specific and developmentally regulated, making them critical players in various physiological processes and diseases, particularly cancer. In colorectal cancer, circRNAs exhibit significantly dysregulated expression patterns and profoundly influence disease progression through diverse molecular mechanisms. Unraveling the complex roles of circRNAs in modulating colorectal cancer immunotherapy outcomes highlights their potential as both promising biomarkers and therapeutic targets. Moving forward, advancements in circRNA-based therapeutic strategies and delivery systems are poised to transform precision medicine, enabling early colorectal cancer diagnosis and improving patient prognosis.

The Research Progress and Modification Strategy on Curing Cancer: The Multidimensional Analysis Based on Precision Health Care

Cancer is one of the key diseases that pose a significant threat to human health in the world. Due to its increasing prevalence and mortality rates, the need for an innovative curing method is urgent among countries. This paper presents a comprehensive overview of the progress and challenges of conventional cancer treatment and carries out a thorough analysis on the therapeutic mechanism and future development prospects. The paper further proposes improvements in multi-modal combined therapy, personalized real-time monitoring solutions and AI-driven efficacy prediction models. This study concludes that these innovative approaches could significantly enhance the effectiveness of cancer treatment by integrating advanced technologies and personalized strategies. Based on a comprehensive analysis of relevant experimental evidence, the paper reveals the clear trend of cancer treatment shifting from a standardized model to a personalized approach, providing a strong theoretical foundation for the development of an international cancer prevention network and therapeutic system.

Chitosan-Based Nanoparticles for Twist1 Knockdown in 4T1 Cells.

Bone metastasized breast cancer reduces the quality of life and median survival. Targeted delivery of twist1-siRNA using nanoparticles (NPs) is a promising strategy to overcome current limitations in treating such metastatic breast cancers. This research evaluates two types of chitosan (CHI)-based NPs for the delivery of twist1-siRNA. Alendronate conjugated PEG functionalized chitosan (ALD-PEG-CHI) NPs are developed for active targeting while PEG functionalized CHI (mPEG-CHI) NPs are fabricated for passive targeting. The size of twist1-siRNA-loaded NPs is below 70nm and the zeta potential is near neutral for both types of NPs. Based on gel retardation assay, complete encapsulation of twist1-siRNA is achieved in both NP systems. The ALD-PEG-CHI-siRNA and mPEG-CHI-siRNA NPs display serum protection for 6 and 4 h, respectively, compared to the immediate degradation of naked twist1-siRNA. The NPs can knockdown twist1 in 4T1 cells as demonstrated through protein expression as well as by phenotypic change in directional cell migration by wound healing assay. Overall, these in vitro results illustrate the potential of the NPs as an effective therapeutic system for bone metastasized breast cancer.

The impact of opioid analgesics with concomitant antipsychotic use on pain modulation and management in internal medicine: a cross-sequential study protocol.

Acute and chronic pain represents an escalating public health concern, necessitating safer and more effective in-hospital management approaches, including mental health. New treatment combinations involving psycholeptics are rising, but real-world evidence is lacking. The study's primary objective is to evaluate the impact of combined opioid analgesics and antipsychotics in-hospital medication on pain modulation. The secondary objective is to evaluate pain management. The cross-sequential study designed by this protocol will analyze retrospective data on 5,000 hospital admissions over four years (2019-2023) gathered from Electronic Health Records (EHR) of a multisite hospital in southern Switzerland. Eligible patients are aged 18 or older and hospitalized in an Internal Medicine ward. All patients with documented pain intensity assessment through a Visual Analogue Scale (VAS ≥ 1) will be included. Cross-sectional data on demographic and clinical variables and type of medication (opioid analgesics, antipsychotics, and selected other drugs according to the Anatomical Therapeutic Chemical classification system) will be screened at hospital admission (T1) and discharge (T2). Pain modulation will be assessed by gravity (VAS mean), intensity (VAS peak/extreme value), and pain treatment effectiveness (ΔT2-T1 VAS). Hospitalization paths (short- and long-term readmissions and total length of hospital stays) will be scrutinized as additional longitudinal indices for pain management and excluded from the cross-sectional analysis. A mixed model approach will assess VAS changes from T1 to T2. Logistic regression and regression models for count data will be used for short- and long-term readmission, respectively. Propensity score matching will be used to mitigate selection bias. This methodological approach combines cross-sectional and longitudinal EHR data gathering in a cross-sequential design. This integration allows for a comprehensive examination of pain modulation and management among internal medicine recipients of concomitant opioids and antipsychotic treatment, spanning both hospitalization and post-discharge periods. By leveraging EHR data, the study protocol ensures reliability and standardization while minimizing missing information. Additionally, the protocol addresses the potential limitations of observational designs. This method offers a comprehensive and rigorous approach to investigating pain modulation and management in internal medicine patients receiving combined opioid analgesics and antipsychotics, with potential implications for enhancing clinical practice and healthcare resource utilization.

Targeted miRNA Delivery in Epilepsy: Mechanisms, Advances, and Therapeutic Potential.

Epilepsy, a neurological disorder characterized by recurrent seizures, presents significant therapeutic challenges, with roughly 30% of individuals demonstrating resistance to antiepileptic drugs. Drug-resistant epilepsy diminishes patients' quality of life and underscores the critical need for innovative therapeutic approaches. MicroRNAs, small non-coding RNA molecules, have emerged as key regulators in the pathogenesis of epilepsy, influencing neuronal excitability, synaptic plasticity, and neuroinflammatory processes. By targeting multiple genes and pathways involved in epileptogenesis, miRNAs offer promising opportunities for precision medicine. This review explores the dual roles of specific miRNAs in epilepsy, acting as both promoters and inhibitors of pathogenic pathways, and highlights recent advancements in miRNA-based therapeutic delivery systems. State-of-the-art approaches, including lipid nanoparticles, viral vectors, and exosome-based systems, are being developed to address challenges such as blood-brain barrier penetration, targeted delivery, and minimizing systemic side effects. These advancements lay the groundwork for more effective and personalized treatment strategies.

Carbon Dots as a Fluorescent Nanosystem for Crossing the Blood–Brain Barrier with Plausible Application in Neurological Diseases

Background/Objectives: The development of effective therapies for brain disorders is highly correlated with the ability of drugs or nanosystems to cross the blood–brain barrier (BBB), which has been limited. Recently, carbon dots (CDs) have been receiving attention to be used as BBB-crossing theranostic agents due to their inherent advantages, such as low size, excellent biocompatibility, high quantum yield (QY), tunable fluorescence, high drug loading, and relatively easy synthesis at low cost. The aim of this study was to design CDs with precisely controlled fluorescence properties for advanced bioimaging and an in-depth assessment of BBB permeability. Methods: CDs were synthesized using a microwave-assisted approach, optimized through microwaves’ irradiation time, and employing citric acid, urea, and sodium fluoride as precursors. The optimized sample was labeled as NF-CD. Results: A comprehensive physicochemical, photoluminescence, and biological characterization revealed the ability of NF-CD to diffuse across a neuromimetic-BBB model, mainly due to their small size (average diameter of 4.0 ± 1.1 nm), exhibiting excitation-dependent fluorescence in the blue and green wavelengths, high biocompatibility and QY, and exceptional photostability. Conclusions: Owing to the exceptional fluorescence characteristics and biological compatibility, NF-CD presents promising opportunities in theranostic applications, particularly in brain-targeted bioimaging, nanocarrier-based drug and immunotherapy delivery, early-stage diagnostics, and personalized medicine. NF-CD’s ability to cross the BBB further underscores the relevance of pioneering nanomaterial-based strategies for neurological disorder diagnostics and precision-targeted therapeutic interventions. Overall, this research contributes to the broader field of nanotechnology-driven biomedical advancements, fostering innovations in neurological diagnostics and therapeutic delivery systems.

Chronic, Battery‐Free, Fully Implantable Multimodal Spinal Cord Stimulator for Pain Modulation in Small Animal Models

AbstractSpinal cord stimulation (SCS) for chronic pain management is an invasive therapy involving surgical implantation of electrodes into spinal epidural space. While the clinical value and mechanistic action of the therapy is debated considerably in recent years, preclinical chronic studies employing rodent models can provide invaluable insights regarding the balance between efficacy and complications as well as mechanistic understanding of SCS therapy. However, current rodent compatible devices require tethered power delivery or bulky batteries, severely limiting the ability to probe long‐term efficacy of SCS therapy. This work introduces a tether‐free, small‐footprint, fully implantable, battery‐free SCS device compatible with rodent models, capable of delivering electrical stimulation to the spinal cord at a wide range of frequency, amplitude, and period via wireless communication adjustable on‐demand without direct interaction with the animal. The presented device features capabilities of clinical SCS devices, with materials and processes amendable to scalable fabrication at a cost suitable for one‐time use enabling high N studies. In this proof of concept, the implantable device serves to assess therapeutic efficacy of various clinically relevant SCS paradigms in alleviating neuropathic pain. This technology offers chronic stability and the potential to serve as the foundation for future research into the development of SCS therapeutic systems.

Apitherapy for drug-induced kidney disease: a narrative review on its mechanisms.

The use of medications for the treatment of various diseases often results in kidney damage. Apitherapy is a natural therapeutic tool with potential utility for this purpose. This narrative review analyzes and summarizes the scientific evidence on the use of apitherapy in drug-induced kidney disease. This review summarizes and analyzes recent advances in drug-induced kidney disease and explores, based on the available scientific evidence, how apitherapy can modify these mechanisms and be utilized for prevention and treatment. Apitherapy (the complementary and integrative use of beehive products) is a potentially useful therapeutic system for the treatment of various diseases. This review examines the preclinical and clinical evidence available regarding its potential use in drug-induced kidney disease. Apitherapy has effects on various pathophysiological mechanisms of drug-induced kidney disease, including oxidative stress, inflammation, decreased renal blood flow, glomerular damage, increased membrane permeability, activity of the renin-angiotensin-aldosterone axis, mitochondrial dysfunction, and apoptosis. Further studies in humans are needed to evaluate its efficacy in the clinical setting, but the available evidence is promising.

Expression and in vitro function of anti-CTLA-4 human antibody expressed in plants

Abstract Biosimilars produced in plant systems encompass a range of molecules, including antibodies, vaccines, enzymes, receptors, and other therapeutic molecules. In the present study, we aimed to express the immune checkpoint-inhibitor anti-CTLA-4 antibody, Ipilimumab, in Nicotiana tabacum plant. We generated transgenic tobacco plants using Agrobacterium-mediated transformation and purified an anti-CTLA-4 monoclonal antibody (mAbP CTLA-4) using protein A affinity chromatography. This purified mAbP CTLA-4 showed specific binding activity to CTLA-4-positive human tonsil tissues, as confirmed by immunoblot, indirect ELISA, and immunohistochemistry analyses. Our study confirmed that mAbP CTLA-4 effectively targeted CTLA-4 in human tonsil tissues. These findings suggest that our plant-derived anti-CTLA-4 antibody retains its original functionality, underscoring the promising potential of plant-based therapeutic expression systems for producing high-value medicinal biosimilars.

Process development of tangential flow filtration and sterile filtration for manufacturing of mRNA-lipid nanoparticles: A study on membrane performance and filtration modeling.

Process development of tangential flow filtration and sterile filtration for manufacturing of mRNA-lipid nanoparticles: A study on membrane performance and filtration modeling.

Exploration of scientific connotation of "Yin-Jing" medical properties of Cyathula officinalis via potentiating therapeutic effect, guidance and targetability.

Exploration of scientific connotation of "Yin-Jing" medical properties of Cyathula officinalis via potentiating therapeutic effect, guidance and targetability.