Ovarian cancer is frequently associated with recurrence and chemoresistance, representing a major clinical challenge. Among the mechanisms underlying treatment resistance, ATP-binding cassette subfamily G Member 2 (ABCG2) plays an important role in drug efflux and tumor adaptation. At the same time, radiomics has emerged as a non-invasive approach for identifying imaging biomarkers that may reflect tumor molecular characteristics. This study investigated the relationship between computed tomography (CT)-derived radiomic features and ABCG2 expression in ovarian cancer. This retrospective radiogenomic study included 70 patients from the Cancer Genome Atlas with available contrast-enhanced CT images and matched gene expression data. A single axial CT slice showing the largest tumor area was selected for analysis. Tumors were manually segmented using Horos, and the statistical analysis included univariate testing with false discovery rate correction and exploratory multivariable modeling using Least absolute shrinkage and selection operator (LASSO) and ridge logistic regression. Five radiomic features showed nominally significant differences between ABCG2-positive and ABCG2-negative tumors, mainly involving tumor shape and attenuation characteristics. However, none remained significant after correction for multiple comparisons. Multivariable models showed limited predictive performance, with area under the curve values of 0.508 for LASSO and 0.598 for ridge regression. Although predictive performance was modest, CT-derived radiomic features appeared to capture subtle imaging differences associated with ABCG2 expression. These findings support the potential role of radiomics as a non-invasive tool for exploring molecular tumor phenotypes in ovarian cancer.
COVID-19 remains a major global health challenge, highlighting the urgent need for more effective treatments. Nanotechnology-based drug delivery systems provide a promising platform for overcoming the limitations of traditional antiviral, anti-inflammatory, and immunomodulatory therapies. Carefully designed nanocarriers can improve how drugs move through the body, reach target cells, and are taken up, increasing antiviral effectiveness and potentially lowering systemic toxicity. In addition to serving as carriers for approved antiviral drugs, many nanomaterials possess their own antiviral properties. Since dysregulated inflammation and cytokine storms are key factors in severe COVID-19, nanomedicine also offers ways to deliver anti-inflammatory and immunomodulatory agents directly to sites of immune activation, enabling more precise control of interleukin and cytokine release. This review covers recent developments in the design and use of nanocarriers and nanomaterials for the prevention, diagnosis, and treatment of COVID-19, and discusses future prospects for nanotechnology in the management of viral infections.
Brain-linked pathologies such as neurodegenerative diseases, malignant brain tumors, cerebrovascular and infectious neuropathologies remain difficult to diagnose and treat because of the restrictive and disease-dependent nature of biological barriers in the central nervous system. Although nanotechnology has achieved considerable preclinical success, the clinical implementation of nanoparticle-based brain treatments has been inconsistent, and a significant gap exists between experimental models and clinical reality. Nanoparticle strategies to overcome delivery barriers are critically analyzed with particular emphasis on theranostic systems and emerging biomimetic approaches. In addition to categorizing nanoparticles by class, we incorporate blood-brain barrier (BBB) structural and functional heterogeneity along with post-BBB transport constraints, including interstitial diffusion, cellular uptake variability, and intracellular trafficking, together with nanoparticle physicochemical design parameters such as size, surface charge, and functionalization, to explain why delivery outcomes are disease- and stage-dependent. Major nanoparticle platforms, including polymeric, liposomal, dendrimeric, metallic, carbon-based, and biomimetic systems, are being considered for Alzheimer’s disease, Parkinson’s disease, glioblastoma, stroke, and infectious brain pathologies. Integration of recent preclinical findings with emerging clinical trial evidence indicates that immune clearance, pharmacokinetic variability, limited tissue distribution, manufacturing complexity, and regulatory challenges are key contributors to translational failure. To address the trade-offs between multifunctional complexity and clinical feasibility, a disease-informed and regulation-aware framework is proposed to guide future nanoparticle development. Advancing brain nanomedicine will require coordinated progress across materials science, neuropharmacology, and translational research to move from proof of concept toward effective patient therapies.
The widespread and indiscriminate use of antibiotics is increasing drug resistance. The study iso-lated, characterized, and assessed the bioactivity of bacteriophages against some multi-resistant Enterobacteriaceae. Using standard protocols, eight wastewater samples were obtained and used to isolate and characterize potential host enteric bacteria and bacteriophages. The wound-healing effect of the phage cocktail (PC) was evaluated by treating coinfected incision 4-cm wounds in animal groups. One hundred bacterial isolates were obtained. Six: U1, U2, S1, S2, P1, and P2, resulted in polyvalent bacteriophages. The cocktailing increased the host range to seventeen. Morphologically, the six bacterial colony sizes ranged from 1 to 6 mm and exhibited different responses to biochemical tests. The PC characterization indicated the presence of constituent phages of the host bacteria. The observed plaque morphology included small, medium, and large-sized plaques, as well as diffuse and clear plaques. The PC concentrations ranged from 3.6 × 103 to 5 × 105 PFU/ml. The adsorption times ranged from 9 to >10 min, with different burst sizes and latent periods. The bacterial isolates showed high resistance, with high multi-antibiotic resistance indices. The host bacteria were identified as Klebsiella aerogenes (U1), Citrobacter freundii (U2), Salmonella enterica (S1 and S2), and Escherichia coli (P1 and P2). Phage therapy with the PC showed significant differences in wound size (p = 0.000), with the PC groups outperforming the negative control groups. The study provides promising evidence for the potential use of phages as alternatives to antibiotics, though further research and clinical trials are necessary to establish their efficacy and safety.
Liposomal synthetic cannabidiol (LPT-CBD) is an injectable drug designed for sustained CBD release into the bloodstream. While Epidiolex, an oral CBD drug, is FDA-approved for epilepsy, the safety of its major human metabolite, 7-carboxy-CBD (7-COOH-CBD), remains unclear. To further investigate the safety of this major metabolite, a suitable animal model is needed that ac-curately reflects human levels. This study investigated the pharmacokinetics (PK) and prelimi-nary safety of subcutaneous LPT-CBD injection in rabbits and minipigs, predicted to emulate CBD human metabolism by producing high 7-COOH-CBD levels. Rabbits received doses of 12, 24, and 30 mg/kg LPT-CBD, with PK monitoring at 24 mg/kg, demonstrating sustained CBD release over 10 days. Peak CBD plasma concentra-tions were observed within 2 days; however, 7-COOH-CBD levels did not accurately mimic hu-man metabolism. The brain distribution of CBD was evaluated in all rabbits, presenting a dose-proportional level. Minipigs, administered doses of 5, 7.5, and 10 mg/kg, exhibited prolonged CBD PK, with plasma concentrations peaking within a day, and a half-lives of 4.4–7.6 days. Im-portantly, 7-COOH-CBD plasma levels exceeded those of CBD at all doses, with area under the curve values 19-100 times higher than those of CBD, aligning with human data. Safety evalua-tions in minipigs, including clinical assessments and histopathology, confirmed good tolerability with minimal injection site reactions. This study supports the prolonged PK profile of CBD fol-lowing a single subcutaneous injection of LPT-CBD, accompanied by detectable levels in the brain. Minipigs exhibited similar CBD metabolism to 7-COOH-CBD as humans do, offering a promising translational model. These findings highlight the therapeutic potential of LPT-CBD and provide initial data on PK and safety profiles.
Everyone eats, so it is no surprise that food-related trade laws exist at the national, international, and regional levels worldwide. Nanotechnology has transformed traditional food systems — from crop cultivation and harvesting to storage, transport, marketing, drug delivery via food, and waste prevention— since the early 2000s. These combined changes enable humanity to provide clean, safe, and affordable food for everyone. But first, is it safe? The European Food Safety Authority (EFSA) uses strong scientific methods to create a framework for monitoring nano-structures in food from “Field to fork.” Unfortunately, nanoscale titanium dioxide is deemed safe by one law but may be banned as a gametotoxin under another, creating crossroads for international trade of nanomaterials in food. Merging law and science to resolve these conflicting regulations has important implications for global trade, the food industry, and human health. This article offers a broad view of the legal landscape surrounding nanomaterials in food, leaving some questions for further consideration. In conclusion, the time is right to harmonize regulatory approaches.
This article serves as a preamble to the International Conference on Recent Advances in Nanomedicine, held in Bhubaneshwar, Odisha, India, 21-22 February 2025 (https://nanomedicineconference.com/).
COVID-19 remains a major global health challenge, highlighting the urgent need for more effective treatments. Nanotechnology-based drug delivery systems provide a promising platform for overcoming the limitations of traditional antiviral, anti-inflammatory, and immunomodulatory therapies. Carefully designed nanocarriers can improve how drugs move through the body, reach target cells, and are taken up, increasing antiviral effectiveness and potentially lowering systemic toxicity. In addition to serving as carriers for approved antiviral drugs, many nanomaterial possess their own antiviral properties. Since dysregulated inflammation and cytokine storms are key factors in severe COVID-19, nanomedicine also offers ways to deliver anti-inflammatory and immunomodulatory agents directly to sites of immune activation, enabling more precise control of interleukin and cytokine release. This review covers recent developments in the design and use of nanocarriers and nanomaterials for the prevention, diagnosis, and treatment of COVID-19. It discusses future prospects for nanotechnology in the management of viral infections.
Nanomedicines advance only when scientific innovation aligns with manufacturability, regulatory expectations, and strategically constructed intellectual property. Yet the patent histories behind successful clinical nanomedicines are rarely examined, and the numerous unpublished or uncommercialized inventions that precede them are often forgotten. Here, we analyze more than four decades of patents produced by Advanced Magnetics/AMAG Pharmaceuticals, culminating in the development of Feraheme® (ferumoxytol), the only superparamagnetic iron oxide nanoparticle (SPIO) currently approved for clinical use. This historical/technical examination reveals that the path to Feraheme was shaped not only by major scientific breakthroughs, such as the introduction of reduced dextran chemistry, but also by large clusters of “black hole” patents, which are creative, often sophisticated inventions that consumed substantial effort yet never translated into products. These abandoned patents constitute a valuable scientific archive: they document approaches that were prematurely discontinued, outpaced by market forces, or constrained by regulatory realities, yet remain relevant to today’s precision nanomedicine challenges. This case study provides “food for thought” for academic laboratories, startups, and translational teams seeking to navigate the increasingly complex intersection of materials science, regu-latory pathways, and intellectual property in modern nanomedicine development.
Advanced cancer is still considered an incurable disease because of its metastatic spread to distal organs and the progressive gain of resistance to given treatments. Even though more effective therapies have become available over the past years, long-term recurrence and undesirable side effects remain the main drawbacks of current clinical protocols. Because of this, there is a strong need to generate new effective anticancer treatments. Particularly, against specific molecular intracellular targets, most of which still remain elusive because many targets are unfortunately challenging to inhibit or undruggable. Therefore, the use of antibodies to target intracellular oncological proteins is regarded as a promising strategy, even though intracellular antibody uptake is, _per se_, suboptimal, as antibodies cannot efficiently enter cells. Here, we present a summary of our efforts to generate antibody delivery systems based on polymer micelles and extra-cellular vesicles, and to use them to deliver recombinant proteins across different disease models.
Breast cancer is one of the most frequently diagnosed cancers among women around the globe. It is usually addressed through chemotherapy, radiation, and surgical interventions—methods that are often hindered by toxicity, non-specificity, and resistance to drugs. This study, presented at ICRAN 2025, introduces a nanotechnology-based strategy that uses RGD peptide-conjugated chitosan nanoparticles (RGD-CHNPs) for the targeted treatment of breast cancer. Raloxifene (Rlx), a selective estrogen receptor modulator, was incorporated into these nanoparticles to boost therapeutic effectiveness. The RGD-CHNPs demonstrated improved stability and cellular absorption in the acidic tumor environment typical of breast cancer. By targeting the αvβ3 integrin by the conjugation of RGD enhanced the efficient delivery of Rlx to cancer cells, inducing apoptosis and inhibiting both migration and angiogenesis. In vivo imaging validated the selective accumulation of Cy5.5-labeled RGD-CHNPs within tumors, and the Rlx-RGD-CHNPs substantially decreased tumor growth without harming normal tissues. These results highlight the complementary advantages of pH responsiveness and RGD-mediated targeting, positioning RGD-CHNPs as an encouraging platform for safe and effective treatment of breast cancer.
Hyperargininemia is a rare autosomal recessive metabolic disorder caused by a deficiency in the urea cycle enzyme arginase 1, resulting in severe systemic and neurological complications. Given the shortcomings of conventional treatment paradigms, there is an increasing demand for gene therapies, such as CRISPR-Cas9, that address hyperargininemia at its genetic root and reverse its diverse manifestations. Homology-directed repair offers high specificity and durable genetic correction. The strategic delivery of CRISPR components, including homology arm-flanked, wild-type ARG1 cDNA, Cas9 endonucleases, and appropriate sgRNAs, is necessary to enable homology-directed repair in arginase 1-deficient hepatocytes. This review summarizes the methodology, strengths, and weaknesses of three prominent CRISPR delivery methods: lipid nanoparticles, recombinant adeno-associated viruses, and electroporation. We also highlight ongoing efforts to optimize these delivery methods and analyze the relevance of existing preclinical CRISPR-Cas9 studies to hyperargininemia. Among these delivery systems, recombinant adeno-associated viruses currently show the most promise for clinical translation, although further enhancements in safety and scalability remain necessary.
Endometriosis is a chronic inflammatory disorder affecting around 10% of reproductive-age women, and its diagnosis is often delayed due to the dependence on invasive laparoscopy. This study explored the potential of a serum-based biomarker panel for the non-invasive detection of endometriosis. Ninety premenopausal women (45 with surgically confirmed endometriosis and 45 controls) were enrolled, and serum levels of IL-6, TNF-α, hs-CRP, MCP-1, LIF, Glycodelin, Activin A, and CA-125 were measured using ELISA. Concentrations of all biomarkers were higher in the endometriosis group compared to controls (p < 0.001). Among them, hs-CRP, TNF-α, Glycodelin, and Activin A showed relatively high diagnostic performance (AUC values ranging from 0.93 to 1.00). Multivariate regression suggested that CA-125, IL-6, and MCP-1 may serve as independent predictors, and clustering analysis indicated possible subgroups with distinct inflammatory profiles. These findings suggest that a combination of selected serum biomarkers could support non-invasive diagnostic approaches for endometriosis, warranting further validation in larger, multicenter studies
Cutaneous leishmaniasis (CL) remains a major neglected disease with limited therapeutic op-tions and expanding geographic distribution. To develop a safe, accessible local treatment, we formulated topical Miltefosine gels incorporating different types of liposomes. Preclinical tests using low-dose Miltefosine (0.015% w/v) and ultrafluid liposomes were ineffective, leading us to increase the drug concentration and revise the liposomal design. At 0.5% w/v, Miltefosine—whether used alone or with fluid liposomes—produced complete lesion healing in a murine L. amazonensis model, with no relapse and sterile lesions at 30 days. Liposomes further accelerated the healing process. A first-in-human compassionate-use case with a patient refractory to standard therapies confirmed good local tolerance and eventual clinical cure using 0.5–1% Miltefosine gels + short Amphotericin B treatment. The experience also showed that ultrafluid liposomes are unsuitable for open ulcers, informing future optimization. Overall, topical Miltefosine at adequate concentration is a promising local treatment for CL, and liposomes can enhance therapeutic performance.
Emerging nanomedicine strategies, particularly theranostic nanoparticles integrating imaging and therapeutic capabilities, have been developed to overcome stromal barriers, improve drug penetration, and enable real-time monitoring of treatment response. Here, we summarize several approaches developed in our group on the production and evaluation of tumor and stroma co-targeted theranostic nanoparticles. We will discuss rationales for target/ligand selection and highlight examples of preclinical studies and the potential applications for precision oncology to improve the outcome of treatment of therapy-resistant human cancers.
Nanocrystals have emerged as an interesting class of delivery systems to solubilize pharmaceuticals belonging to classes II and IV of the Biopharmaceutics Classification System (BCS). This can be attributed to their small size and high drug content. More than 20 nanocrystal formulations have already been approved by the Food and Drug Administration (FDA) for oral and parenteral administration, with additional clinical trials in progress. This review provides an update on FDA-approved nanocrystals and current literature findings on their production using bottom-up techniques. Controlling drug supersaturation is a key step in this context. The beneficial surface-to-volume ratio enhances the dissolution rate of drugs compared to their solid form. Most monocrystal studies focus on diseases related to cancer and inflammation. We have concentrated on these areas, as well as new strategies aimed at combining drugs, including co-crystallization of drugs in nano-forms. Finally, we reviewed targeting approaches proposed for nanocrystals, which are primarily based on two main strategies: either grafting a ligand onto their surface or incorporating them into natural or modified membranes to facilitate homing to specific cells or tissues.
Radiogenomics and lipid metabolism are complementary aspects in studying clear cell renal cell carcinoma (ccRCC). The GTPase of immunity-associated proteins (GIMAP) gene family, known for its role in lymphocyte survival and immune regulation, has recently been linked to specific radiogenomic features. This study aimed to determine whether GIMAP expression correlates with radiological markers of lipid metabolism, such as tumor and liver attenuation on non-contrast computed tomography (CT) and abdominal fat distribution. Genomic and imaging data from The Cancer Genome Atlas (TCGA) and The Cancer Imaging Archive (TCIA) were analyzed in a cohort of 205 ccRCC patients. Both traditional and AI-assisted statistical methods (Welch’s t-test with FDR-BH correction, equivalence testing, and robust winsorization) showed no signifi-cant differences between GIMAP-positive and GIMAP-negative tumors. Average tumor attenuation was similar (36.6 vs. 34.6 HU, p=0.180), as were total, visceral, and subcutaneous fat areas (all p>0.13), along with liver attenuation measures (all p>0.5). These results suggest no meaningful link between GIMAP expression and CT-based lipid metabolism indicators, supporting the idea that GIMAP mainly reflects immune rather than metabolic aspects of tumor biology. CT lipid markers are unlikely to be reliable indicators of GIMAP expression. Future radiogenomic models should incorporate both immune and metabolic factors to improve patient classification in ccRCC.
Bromocriptine Mesylate is an alkaloid ergot derivative that acts as a dopamine D2 agonist. The work aims to develop nanostructured lipid carriers (NLCs) of bromocriptine mesylate to improve its bioavailability, which is only 28% orally. The nasal route is one of the best methods to deliver drugs directly to the brain. To increase brain uptake through the direct nose-to-brain channel, bromocriptine mesylate-loaded nanostructured lipid carriers (BCM-NLCs) were prepared and assessed for the application. The formulations were prepared based on 32 full-factorial experimental designs to study the effect of the formulation variables, such as total lipid ratio and concentration of surfactants. BCM-NLCs were prepared using the ultrasonic dispersion method, and processing parameters such as total lipid ratio and concentration of surfactants were optimized, then characterized. The BCM-NLCs were analyzed in rats for comparative drug release studies via oral and intranasal routes. The optimized BCM-NLCs showed a mean particle size of 108.4±0.26 nm, a polydispersity index of 0.344, zeta potentials of -42.8±0.52 mV, entrapment efficacy of 91.1±0.04 %, and drug content of 99.9%. The in vitro studies revealed that bromocriptine was released from NLCs in two phases: an initial burst followed by a steady release for 24 hours. The Korsmeyer-Peppas (0.9147) model is suitable for release kinetics. In-vivo studies showed that the concentration of optimized BCM-NLCs increased when administered via the intranasal route (C~max=703.05±2.21µg/ml; t~max=12hr) compared to the oral (C~max=231.16±1.13µg/ml; t~max=12hr) approach. The BCM-NLCs remained stable at 4-8±2°C for three months. We concluded that bromocriptine mesylate-loaded nanostructured lipid carriers could be potentially used as intranasal drug delivery carriers to manage Parkinson’s disease.
Quercetin, a bioactive flavonoid, has well-documented antitumour properties; however, its clinical application is limited by its hydrophobicity, poor bioavailability, and stability. These limitations can be addressed via the use of nanotechnology-based drug delivery systems. In this study, we sought to develop polylactide-coglycolide nanoparticles functionalized with polyethylene glycol as the drug vehicle for encapsulating quercetin, and further investigated their anticancer potential against the human tongue squamous cell carcinoma cell line HNO-97 by comparing their effica-cy with that of free quercetin and doxorubicin as standard chemotherapeutic control. Quercetin NPs (QNPs) were synthesized and characterized for particle size, zeta potential, and entrapment efficiency via dynamic light scattering and for morphology via transmission electron microsco-py. The cytotoxicity was evaluated at two time intervals (4 and 24 hours) via the MTT assay. Apoptosis analysis was performed via flow cytometry, and the gene expression levels of Bax, Bcl-2, and PI3K were evaluated via RT-qPCR. After 24 hours of treatment, the in vitro cell cyto-toxicity study revealed that, compared with free quercetin (59.7 µM) and DOX (74.7 µM), QNPs exhibited superior cytotoxicity (IC₅₀ = 41.4 µM). The anticancer efficacy of the QNPs was fur-ther confirmed by enhanced cellular apoptosis. Moreover, treating cells with QNPs resulted in increase in the Bax expression level and the decrease in the Bcl-2 and PI3K expression levels, resulting in the highest Bax/Bcl-2 ratio (31.03). In conclusion, the overall study results suggest that quercetin encapsulated PLGA-PEG nanoparticles may serve as potential drug candidates for the treatment of human tongue squamous cell carcinoma.
Transdermal drug delivery systems are gaining increasing interest due to their ability to bypass first-pass metabolism in the liver and provide better patient compliance while delivering drugs through a controlled-release mechanism. The outermost layer of human skin, known as the stratum corneum, creates a barrier to drug absorption that has proven challenging for water-soluble drugs and large molecules, including natural product compounds. The combination of nanoemulsion characteristics with hydrogel properties in nanoemulgels formulations serves as a novel method to enhance transdermal drug delivery. This review aims to evaluate the permeation efficacy of nanoemulgel systems in animal skin models. To do that, it evaluates nineteen studies examining how different skin structures affect drug permeation outcomes. Nanoemulgels formulations demonstrated superior results compared to traditional gels when combined with penetration enhancers such as clove oil or eucalyptus oil, according to the reviewed studies. These findings highlight the significance of model selection in permeation studies and demonstrate that nanoemulgels are promising vehicles for transdermal drug delivery. Animal skin permeation test results exhibit a similar pattern to those obtained from in vivo studies. However, differences in human skin make these results inapplicable to humans, requiring a thorough examination of differences between animal species.
