Search Results (427)

The mesenchymal–epithelial transition (MET) receptor is a tyrosine kinase activated by its sole known ligand, hepatocyte growth factor (HGF). MET signaling regulates key cellular processes, including proliferation, survival, migration, motility, and angiogenesis. Dysregulation and hyperactivation of this pathway are implicated in multiple malignancies, including lung, breast, colorectal, and gastrointestinal cancers. In non–small cell lung cancer (NSCLC), aberrant activation of the MET proto-oncogene contributes to 1% of known oncogenic drivers and is associated with poor clinical outcomes. Several mechanisms can induce MET hyperactivation, including MET gene amplification, transcriptional upregulation of MET or HGF, MET fusion genes, and MET exon 14 skipping mutations. Furthermore, MET pathway activation represents a frequent mechanism of acquired resistance to EGFR- and ALK-targeted tyrosine kinase inhibitors (TKIs) in EGFR- and ALK-driven NSCLCs. Although MET has long been recognized as a promising therapeutic target in NSCLC, the clinical efficacy of MET-targeted therapies has historically lagged behind that of EGFR and ALK inhibitors. Encouragingly, several MET TKIs such as capmatinib, tepotinib, and savolitinib have been approved for the treatment of MET exon 14 skipping mutations. They have also demonstrated potential in overcoming MET-driven resistance to EGFR TKIs or ALK TKIs. On 14 May 2025, the U.S. Food and Drug Administration granted accelerated approval to telisotuzumab vedotin-tllv for adult patients with locally advanced or metastatic non-squamous NSCLC whose tumors exhibit high c-Met protein overexpression and who have already received prior systemic therapy. In this review, we summarize the structure and physiological role of the MET receptor, the molecular mechanisms underlying aberrant MET activation, its contribution to acquired resistance against targeted therapies, and emerging strategies for effectively targeting MET alterations in NSCLC. Full article

Kynurenic acid (KYNA), a small molecule derived from the tryptophan–kynurenine pathway, can readily diffuse across biological membranes and act as an endogenous ligand for receptors such as the aryl hydrocarbon receptor (Ahr). While KYNA dysregulation is implicated in neurodegenerative disorders, the role of the KYNA–Ahr-IL-6 axis in MSC proliferation and differentiation remains poorly defined. We investigated the impact of KYNA on murine bone marrow-derived MSCs (BM-MSCs) at various concentrations (10–200 μM) and time points (8–48 h). The BM-MSC phenotype was assessed via flow cytometry; proliferation, via cell counting; and the gene expression of Ahr, Cyp1a1, Cyp1b1, and Il-6, via quantitative real-time PCR. Multipotency was evaluated through adipogenic, osteogenic, and chondrogenic differentiation assays with histochemical confirmation. KYNA significantly upregulated Ahr mRNA expression. Among the tested concentrations, 100 μM KYNA induced the highest Ahr expression (~19.1 ± 1.5-fold greater than that of the untreated controls, p < 0.005). Notably, 10 and 50 μM KYNA caused moderate induction, whereas compared with 100 μM KYNA, 200 μM did not further increase expression. In addition, KYN treatment increased Cyp1a1, Cyp1b1, and Il-6 expression, with increases of ~64.6 ± 4.5-fold, ~43.6 ± 2.3-fold, and ~41.6 ± 1.2-fold, respectively. Compared with no treatment, 100 µM KYNA enhanced BM-MSC proliferation by 1.210 ± 0.02, 1.189 ± 0.03, and 1.242 ± 0.02-fold across passages P3, P4, and P5, respectively (p < 0.05), without altering Sca-1, CD90, or CD45 expression or impairing trilineage differentiation potential. KYNA may activate the AHR–IL-6 signaling axis to promote BM-MSC expansion. This controlled proliferative effect, without loss of phenotypic or functional integrity, highlights the pharmacological potential of KYNA as a small-molecule modulator for stem cell-based therapies. Full article

Estrogen-related receptor beta (ESRRB) is thought to be an orphan receptor that functions as a transcription factor, pioneer factor, and mitotic bookmarker to regulate cell stemness, pluripotency, and differentiation. This study (1) investigates whether calcium and cadmium activation of ESRRB regulates signaling pathways of stemness and pluripotency, (2) explores the transcriptomic and biological alterations of metal activation of ESRRB, and (3) reveals the underlying mechanisms by which metals activate ESRRB. In HEK293T cells, treatment with calcium and cadmium increased the expression of ESRRB-regulated genes that was blocked by an ESRRB antagonist. In the breast cancer cell line MDA-MB-453, treatment with calcium, cadmium, or a synthetic agonist also increased the expression of ESRRB-regulated genes that was blocked by the antagonist, enhanced ESRRB nuclear localization, increased the recruitment of RNA polymerase 2 to estrogen-related receptor response elements (ERRE), enhanced cell stemness and proliferation pathways, and induced the expression of estrogen receptor alpha (ESR1 or Erα). Mutational analysis and molecular docking identified potential metal interaction sites within ESRRB’s ligand-binding domain. Together, these results suggest calcium acts as a natural ligand for ESRRB and cadmium, which mimics calcium, activate ESRRB to mediate cell stemness and pluripotency. Full article

The neuroendocrine and immune systems interact bidirectionally through shared ligands and receptors during inflammation, thereby regulating immune responses. Leptin, primarily known for its role in energy metabolism and appetite regulation, also modulates neuroinflammatory pathways. Its receptors are widely expressed on immune cells and contribute to immune mechanisms implicated in the pathogenesis of neuroinflammatory disorders such as multiple sclerosis (MS) and Alzheimer’s disease (AD). This review highlights recent advances in understanding leptin’s role in immune regulation, with a focus on its impact on MS and AD. A comprehensive literature review was conducted until October 2025, using PubMed, Google Scholar, and Scopus to identify studies investigating leptin in neuroinflammatory conditions, particularly MS and AD. Leptin exerts broad immunomodulatory effects by activating T cells, dendritic cells, and microglia, and promoting their proliferation and phagocytosis. Its elevation enhances Th1 and Th17 responses, drives pro-inflammatory macrophage phenotype polarization, and suppresses regulatory T cell and Th2 responses, immune pathways involved in MS. Peripheral leptin levels are increased in MS, especially during disease exacerbations. In contrast, in AD, they are typically reduced, particularly in patients with normal body mass index (BMI), where their decline contributes to amyloid-β and tau pathology. These divergent patterns position leptin as a bidirectional regulator at the intersection of immunity and neurodegeneration. Additionally, its protective or detrimental effects likely depend on whether it acts under physiological conditions or in the context of obesity-induced leptin resistance. Elevated leptin levels in obesity exacerbate inflammation and diminish its neuroprotective effects. In conclusion, leptin is elevated in MS patients but downregulated in AD, reflecting its bidirectional effects. In leptin resistance, peripheral proinflammatory signaling is maintained while central leptin signaling is restricted, thereby potentially promoting autoimmunity in MS and limiting neuroprotection in AD. Further mechanistic and longitudinal studies are needed to clarify the relationship between leptin dysregulation, leptin resistance, neuroinflammatory and neurodegenerative diseases. Full article

Background: Prostate cancer (PCa) remains the second leading cause of cancer-related deaths in men in the United States. Fatty acid-binding protein 5 (FABP5), a member of a class of intracellular lipid transporters, promotes PCa progression via enhanced lipid metabolism and trafficking of lipid ligands. Previous work from our group has demonstrated that small-molecule FABP5 inhibitors based on the truxillic-acid monoester scaffold reduce PCa growth. Methods: Here, we assessed the effect of third-generation FABP5 inhibitors on the PCa cell cycle, proliferation, apoptosis, signaling pathway activity, and transcriptomic landscape. Results: We demonstrate that the third-generation FABP5 inhibitor SBFI-1143 significantly inhibits the viability of PCa cells by arresting them at the G0/G1 and G2/M phases of the cell cycle, inducing apoptosis, and promoting cell death. Strikingly, SBFI-1143 efficiently inhibited the growth of PCa spheroids compared to its predecessor, SBFI-103. RNA-seq and Gene Set Enrichment Analysis demonstrated that SBFI-1143 more effectively suppressed pathways involved in cell cycle progression, cell cycle division, and chromosome organization while upregulating genes associated with endoplasmic reticulum stress, responses to incorrectly folded proteins, and regulating apoptosis, compared to SBFI-103. Notably, SBFI-1143 treatment downregulated genes associated with the subpopulation of PCa cells characterized by a lineage plasticity-related signature, related to trans-differentiation, recurrence, and poor cancer prognosis. Conclusions: Our findings demonstrate that SBFI-1143 significantly alters the transcriptomic landscape of prostate cancer and may serve as a potentially effective therapeutic option for this disease. Full article

Small cell lung cancer (SCLC) is an aggressive neuroendocrine tumour with limited treatment options and a poor prognosis. Hypoxia, a hallmark of solid tumours, contributes to therapeutic resistance and tumour progression. Gastrin-releasing peptide receptor (GRPR) is known to be overexpressed in SCLC; however, its regulation under hypoxic conditions is not well described. In this study, we demonstrate that hypoxia significantly enhances GRPR expression in SCLC cell lines, COR-L24 and DMS79, as confirmed by Western blot, immunofluorescence, and flow cytometric analysis of binding with fluorescein isothiocyanate–labelled bombesin (BBN-FITC), a known GRPR ligand. To exploit this upregulation, we synthesised a previously discovered butylated neuropeptide antagonist (BU peptide) using a new method of solid-phase peptide synthesis (SPPS) by Boc chemistry and evaluated its therapeutic potential. BU peptide exhibited potent, dose-dependent cytotoxicity in both cell lines, with significantly greater efficacy under hypoxic conditions compared to normoxia. Mechanistic studies revealed that BU peptide inhibits GRP–GRPR-mediated activation of the PI3K/Akt and MAPK/ERK signalling pathways, known to be key regulators of tumour cell survival and proliferation. Moreover, BU peptide induced robust caspase 3/7-mediated apoptosis, especially under hypoxic conditions. These findings suggest that GRPR is a hypoxia-inducible target in SCLC and demonstrate that a synthetically optimised BU peptide antagonist exerts selective efficacy against hypoxic tumour cells, outperforming conventional chemotherapy agents. These findings provide new mechanistic insights into SCLC and suggest translational potential to inform the development of future treatment strategies for this and other hypoxia-driven malignancies. Full article

Non-small cell lung cancer (NSCLC) remains a leading cause of cancer mortality, with therapeutic resistance posing the primary barrier to durable outcomes. Beyond genetic and epigenetic alterations, amino acid transporter-driven metabolic reprogramming—mediated by LAT1 (SLC7A5), ASCT2 (SLC1A5), and xCT (SLC7A11)—supports tumor proliferation, redox homeostasis, and immune escape. Their preferential expression in NSCLC highlights their potential as therapeutic targets and predictive biomarkers. In parallel, α-particle therapy has gained attention for its capacity to eradicate resistant clones through densely clustered, irreparable DNA double-strand breaks. Astatine-211 (²¹¹At) combines a clinically relevant half-life, high linear energy transfer, and predictable decay scheme, positioning it as a unique candidate among α-emitters. Preclinical studies of ²¹¹At-labeled transporter ligands, particularly LAT1-targeted conjugates, demonstrate potent tumor suppression and synergy with targeted therapy, chemotherapy, radiotherapy, immunotherapy, and ferroptosis inducers. Advances in radiochemistry, delivery systems (antibodies, peptides, and nanocarriers), and PET tracers such as [¹⁸F]FAMT and [¹⁸F]FSPG collectively support a theranostic framework for patient stratification and adaptive dosing. By linking transporter biology with α-particle delivery, ²¹¹At-based theranostics offer a mechanistically orthogonal strategy to overcome resistance and heterogeneity in NSCLC. Successful translation will depend on precise dosimetry, scaffold stabilization, and biomarker-guided trial design, enabling progression toward first-in-human studies and future integration into multimodal NSCLC therapy. Full article

Background/Objectives: Dendritic cell (DC)-based immunotherapies offer a promising strategy for cancer treatment but are limited by inefficient activation of cytotoxic T cells and, in turn, the host immune system. This report demonstrated that CD34⁺ hematopoietic stem cell (HSC)-derived allogeneic DCs engineered by an optimized lentiviral vector (LVV) expressing CD93, CD40-ligand (CD40L), and Chemokine (C-X-C motif) ligand-13 (CXCL13) significantly enhanced the host immune system, activated tumor-specific cytotoxic T cells, and led to complete regression of both primary and metastatic pancreatic tumors in humanized mouse models. This LVV shows comparable pre-clinical efficacy compared to the first-generation vector, in addition to being compliant for clinical use, which allows further pre-clinical development towards the human trials. Methods: This 2nd generation (Gen) LVV incorporates codon-optimized transgenes (CD40L, CD93, and CXCL13) with rearranged sequence to enhance expression, driven by a strong EF1α promoter. CD34⁺ HSCs were transduced with this modified 2nd Gen LVV and differentiated to Engineered DCs. Therapeutic efficacy of the DC therapy with the modified vector was tested on humanized mouse models of pancreatic tumors. This was accomplished by establishing an early-stage disease model (using MIA PaCa-2 (MP2)-tumors) and late-stage metastatic disease model of the pancreatic tumors to mimic the clinical setting using luciferase-expressing MP2-(Luc)-pancreatic tumor-bearing humanized mice. Results: The modified lentiviral construct had 6-fold greater expression of CD40L, 2% less toxicity, 4.5-fold greater CD40L, and 2.2-fold greater CXCL13 secretion than its predecessor. In vitro, Engineered DCs induced robust T cell proliferation in up to 20% of T cells, up to 4-fold greater interferon-gamma (IFN-γ) secretion than controls, and showcased antigen-specific cytotoxicity by CD8⁺ T cells. In vivo, two intradermal doses of the 2nd Gen DCs led to complete regression of primary pancreatic tumors and metastases. Treated mice exhibited prolonged survival, indicating the induction of durable anti-tumor immunity. Conclusions: Vector optimization retained the efficacy of DC-based therapy, achieving curative responses in pancreatic tumor models. These findings support the clinical development of this 2nd Gen DC immunotherapy for pancreatic and potentially other tumors. Full article

Endometriosis is a common gynecological condition that affects fertility in many women of reproductive age worldwide. This multifaceted disease exhibits a pathogenesis characterized by hormonal and immune system dysregulations, alongside increased angiogenic activity within the peritoneum. The aberrant proliferation of endometrial tissue outside the uterus is associated with vascularization in ectopic endometriotic lesions. Consequently, RNA interference (RNAi)-based angiogenic therapies targeting the VEGFA gene present a promising strategy for the treatment of endometriosis. To ensure the efficacy of RNAi-based therapy, it is critical to develop carriers capable of precisely delivering small interfering RNA (siRNA) to target cells. Additionally, the instability of polyplexes in vivo must be regarded as a pivotal aspect influencing the success of non-viral delivery. In this study, we introduce ternary polyplexes comprising siRNA and a carrier derived from an arginine–histidine-rich peptide, which is further coated with a glutamate–histidine-rich polymer modified using an SDF-1 chemokine-derived ligand for targeting CXCR4-expressing cells. The physicochemical characteristics of the siRNA-polyplexes, along with cellular toxicity and GFP gene silencing efficacy, were assessed in vitro. The anti-angiogenic potential of anti-VEGFA siRNA-polyplexes was evaluated by measuring the size of endometrial lesions, conducting immunohistochemical staining, and analyzing VEGFA gene expression. For in vivo experiment, a rat model of endometriosis induced by subcutaneous auto-transplantation of uterine tissue was utilized. A significant reduction in the growth of endometriotic implants and silencing of VEGFA gene expression was observed when compared to the saline-treated control group. The results of this study strongly suggest that the developed ternary polyplexes have significant potential as an efficient tool for the development of anti-angiogenic RNAi-based therapies for endometriosis. Full article

CB₁ agonist compounds may be potential drug candidates for the treatment of gliomas, as they have been shown to inhibit tumor cell proliferation, induce apoptosis, and reduce angiogenesis in various preclinical models. Their ability to modulate the endocannabinoid system suggests a promising therapeutic approach for targeting glioma growth and progression. Herein, we report the design, synthesis, biological studies, and bioinformatics assays of novel benzo[d]imidazole–naphthalen-arylmethanone regioisomers with affinity for the CB₁ receptor, as well as propose an indirect methodology to evaluate their presumed CB₁ agonist activity. Compounds that showed a propensity for binding to the CB₁ receptor were regioisomers 4d, 5b, 5e, 5f, and 5f′. Likewise, derivatives that displaced more than 50% of the radioligand [³H]CP-55940 at the CB₁ receptor were subjected to in vitro viability experiments. Compounds 4d, 5b, 5e, and 5f′ showed toxicity against U87MG cells (malignant glioma) in a considerable percentage. Notably, compound 5f′ showed CB₁ affinity, with a K_i of 2.12 µM, and was selectively toxic to U87MG cells, which highly express the CB₁ receptor, while exhibiting no toxicity toward the healthy HEK293 cell line, which expresses both cannabinoid receptors at negligible levels. Docking studies at the CB₁ orthosteric site indicate that 5f′ forms π-π interactions, a T-shaped interaction, and hydrogen bonding through the oxygen atom of the furan ring. Biologically, our experimental indirect model-based on a simple viability assay is supported by well-established evidence that activation of CB₁ and CB₂ receptors by agonists induces cell death and inhibits tumor cell growth. Structurally, we conclude that the presence of a furan ring at the 2-position of the benzo[d]imidazole core is beneficial for the development of new ligands with potential CB₁ agonist activity. Full article

Background and Objectives: TAM receptors—Tyro3, Axl, and Mer—and their ligand Growth Arrest-Specific 6 (Gas6) represent a pleiotropic system implicated in fibrosis. Increased Gas6 and Axl expression have previously been observed in lung samples and fibroblast cultures from Idiopathic Pulmonary Fibrosis (IPF) patients. The study explored the contribution of Gas6/TAM system in fibrosis development and the impact of its pharmacological inhibition in fibroblasts. Materials and Methods: IPF fibroblasts (IPF FBs) and control human pulmonary fibroblasts (HPFs) were treated with R428 (Axl-specific inhibitor), LDC1267 (TAM inhibitor), or Nintedanib (an IPF-approved drug) to evaluate the influence of these drugs on cell proliferation, migration, and the expression of pro-inflammatory and pro-fibrotic genes. Fibroblast-to-myofibroblast differentiation was induced by TGF-β. The impact of IPF FBs and HPF on macrophage polarization was investigated through a co-culture of fibroblasts with monocyte-derived macrophages, with the further gene expression analysis of markers of the M1 (pro-inflammatory) or M2 (pro-fibrotic) polarization forms. Results: Cell proliferation was monitored in fibroblasts treated with TGF-β, the drugs, and their combination. In the presence of LDC1267 and Nintedanib, minor differences in cell confluence were detected between IPF FBs and HPFs; R428 (1 μM) seemed to have a higher inhibitory impact on IPF FBs. Regarding cell migration, the fibroblasts treated with LDC1267 exhibited slower wound closure. R428 treatment led to a relative wound closure of 76% in HPFs but only 56% in IPF FBs (60 h). R428 (1 μM) significantly reduced the expression of the pro-fibrotic markers ACTA2, COL1A1, and FN1 in HPFs and IPF FBs compared to TGF-β treatment. HPFs and IPF FBs co-cultured with monocyte-derived macrophages demonstrated a significantly increased expression of MRC1 while the expression of FN1, TNFα, and CXCL10 was moderately increased. Conclusions: These findings suggest that R428 and LDC1267 modulate the proliferation, migration, and gene expression of activated fibroblasts via TAM signaling. Fibroblast-mediated effects on macrophage polarization underscore the relevance of intercellular crosstalk in fibrotic disease. Full article

Particulate matter (PM) exposure is linked to chronic kidney disease; however, its effect on immunoglobulin A (IgA) nephropathy (IgAN) remains unclear. We investigated whether PM exposure exacerbates IgAN in a mouse model. HIGA mice (IgAN model) and BALB/c controls were exposed to PM in a sealed chamber for 13 weeks. Lung Toll-like receptor 9 (TLR9) expression, serum aberrantly glycosylated IgA, A proliferation-inducing ligand (APRIL) levels, mesangial IgA deposition, and kidney pathology were assessed. RNA sequencing of splenic B cells was performed to evaluate immune-related gene expression. PM exposure increased lung TLR9 expression in both strains, particularly around pigment-laden macrophages. HIGA mice showed elevated aberrant IgA and APRIL levels, with aggravated mesangial expansion and IgA deposition. Transcriptomic analysis revealed immune dysregulation in splenic B cells of PM-exposed HIGA mice. Our findings provide experimental evidence that PM exposure aggravates IgAN via TLR9-mediated mucosal immune activation, leading to aberrant IgA glycosylation and mesangial deposition. These findings emphasize that reducing PM exposure may benefit patients with IgAN. Full article

Zanthoxyli Pericarpium (ZP), the dried pericarp of mature fruits of Zanthoxylum schinifolium Siebold and Zucc., has traditionally been used in East Asian medicine for its medicinal properties, but its therapeutic potential in periodontitis has not been elucidated. In the present study, we investigated the effects of ZP on ligature-induced experimental periodontitis (EPD) in male Sprague Dawley rats. Animals were assigned to vehicle control, ligature control, ZP-treated (25, 50, and 100 mg/kg), or indomethacin-treated (5 mg/kg) groups (n = 10 per group) and orally administered the respective treatments daily for 10 days after ligature placement. ZP significantly reduced anaerobic bacterial proliferation and inflammatory cell infiltration in gingival tissue. ZP suppressed the production of inflammatory mediators, such as tumor necrosis factor-α and interleukin-1β, in both gingival tissues and lipopolysaccharide-stimulated RAW 264.7 macrophages, through inhibition of the mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathways. In addition, ZP decreased myeloperoxidase activity and reduced matrix metalloproteinase-8 expression, thereby preserving collagen areas. ZP also restored the receptor activator of NF-κB ligand/osteoprotegerin (RANKL/OPG) balance, leading to a reduction in osteoclast numbers and their occupancy on the alveolar surface, and it effectively ameliorated horizontal alveolar bone loss. Furthermore, ZP exhibited antioxidant effects by lowering malondialdehyde levels and inducible nitric oxide synthase activity in gingival tissues. Statistical analysis was performed using ANOVA followed by a post hoc test, with significance set at p < 0.05. These findings indicate that ZP mitigates periodontitis through combined antimicrobial, anti-inflammatory, antioxidant, and anti-resorptive actions, supporting its potential as a therapeutic candidate for periodontitis. Full article

Background: HER1 and HER2 are critical receptors involved in tumorigenesis and the development of targeted therapies for various carcinomas. However, most antibodies and drugs currently in development do not recognize murine orthologs, which restricts their evaluation in immunocompetent models. Methods: We generated nine tumor models through the lentiviral transduction of murine prostate (RM1), lung (3LL-D122), and breast (4T1) carcinoma cell lines, subsequently validating them in immunocompetent BALB/c and C57BL/6 hosts. Receptor expression and functionality were characterized using flow cytometry, immunoblotting, proliferation assays, and therapeutic sensitivity testing. Results: Transduced cells exhibited stable membrane expression of HER1/HER2 and ligand-induced phosphorylation, confirming receptor functionality. In all three tumor models generated, the expression of HER1 and/or HER2 significantly enhanced cell proliferation compared to parental lines. Furthermore, treatment with specific monoclonal antibodies and the tyrosine kinase inhibitor markedly reduced the viability of cells expressing HER1 and/or HER2, without affecting negative controls. Conclusions: These models provide a robust and reproducible platform for the preclinical evaluation of HER1/HER2-targeted therapies in immunocompetent hosts. Although the current model relies on subcutaneous implantation and does not fully replicate the native tumor microenvironment, it represents a crucial first step toward the development of orthotopic and immunologically relevant models for translational cancer research. Full article

Despite aggressive current therapies against glioblastoma (GB), residual tumor cells may remain at the edge of the surgical cavity after resection. These cells can rapidly proliferate, giving rise to tumor recurrence in more aggressive and drug-resistant forms. As photodynamic therapy (PDT) has advanced, it has emerged as an option to treat this brain tumor. The oncological basis of PDT involves the selective accumulation of a photosensitizer (PS) in the tumor, followed by its activation with electromagnetic radiation to generate reactive oxygen species (ROS), which induce tumor cell death. Given that first- and second-generation PSs present significant limitations, including poor tumor selectivity, suboptimal biodistribution, limited absorption within the therapeutic window, and slow systemic clearance, research has progressed toward the development of third-generation PSs based on nanotechnology to optimize their therapeutic properties. This review addresses the types of tumor cell death induced by PDT, as well as the advancements of PS design, focusing on titanium dioxide (TiO₂) and zinc oxide (ZnO) nanoparticles. These nanomaterials can be designed as carriers, encapsulating or conjugating conventional PSs, or act as PSs themselves, due to their favorable biocompatibility and intrinsic photoreactivity. Additionally, they can be functionalized with targeting ligands to achieve tumor-specific delivery, enhancing therapeutic selectivity while minimizing toxicity to healthy tissue. Overall, these nanotechnology-based PSs represent a versatile and promising therapeutic paradigm that warrants further investigation through basic research, supporting the development and potential clinical translation of a more precise and effective PDT-based intervention for glioblastoma, initially aimed at eliminating intra-surgical post-resection residual tumor cells. Full article