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Bridging the gap: ferroptosis of immune cells in the tumor microenvironment.

Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, is increasingly recognized as a pivotal immunomodulatory mechanism within the tumor microenvironment (TME). Beyond its well-established role in tumor cell elimination, emerging evidence reveals that immune cell subsets exhibit distinct susceptibility to ferroptosis, with profound consequences for antitumor immunity. This review systematically delineates the dual and cell-type-specific roles of ferroptosis across innate and adaptive immune populations: while ferroptosis-mediated depletion of immunosuppress

Natural killer cell engagers for cancer immunotherapy.

This review article explores the rapidly evolving field of bi-, tri-, and multi-specific NK cell engagers (NKCEs), highlighting their potential as a cutting-edge approach in cancer immunotherapy. NKCEs offer a significant advancement over conventional monoclonal antibodies (mAbs) by enhancing Antibody-Dependent Cellular Cytotoxicity (ADCC). They achieve this by stably and selectively binding to both NK cell activating receptors and tumor-associated antigens (TAAs). Unlike traditional mAbs, which depend on the relatively transient interaction between their Fc region and CD16a, NKCEs establish m

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… At acidic pH, FcRn binds IgG with high affinity, facilitating recycling and transcytosis, while at physiological pH, it releases the antibody. …

Nanomedicine Approaches for Autophagy Modulation in Cancer Therapy.

Cancer is a daunting global health problem with a steadily rising incidence. Despite the wide arsenal of current anticancer therapies, challenges such as drug resistance, tumor heterogeneity, poor targeting, and severe side effects often lead to suboptimal efficacy and poor patient outcomes, highlighting the need for innovative therapies. Autophagy modulation has emerged as an attractive approach to complement existing therapies. The dual role of autophagy in cancer promotion and suppression has inspired the development of new drugs and therapeutic strategies focusing on both inhibition and in

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… . | [ 292 ] Overcoming biological barriers | Fe‐CDs decorated with angiopep‐2 (Fe‐CDs@Ang) enhanced BBB transcytosis and accumulation in brain tissue parenchyma in GBM mouse models. | [ 269 ] Enhance tumor targeting and accumulation | Passive targeting | BAQ NPs accumulate in mouse models of pancreatic … To enhance BBB transcytosis and accumulation in brain tissue parenchyma, Fe‐CDs were decorated with angiopep‐2 (Fe‐CDs@Ang), a synthetic LRP‐1 ligand. …

Novel insight and perspectives of nanoparticle-mediated gene delivery and immune-modulating therapies for pancreatic cancer.

Current standard-of-care therapies have failed to improve the survival of patients with metastatic pancreatic cancer (PCA). Therefore, exploring novel therapeutic approaches for cancer targeting is of utmost need. During the past few years, many efforts have been made to develop conventional treatment strategies to reduce chemotherapy resistance. However, critical challenges have impeded current cancer management outcomes, and limited clinical responses have been achieved due to unfavorable off-target effects. Advances in nanotechnology-based gene and immune-modulator delivery systems have exc

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… Transcytosis mediated deep tumor penetration for enhanced chemotherapy and immune activation of pancreatic cancer. Advanced Functional Materials. 2023;33:2214937. 25. Coelho SC, Reis DP, Pereira MC, Coelho MAN. …

Metastatic Breast Cancer: Review of Emerging Nanotherapeutics.

Metastases of breast cancer (BC) are often referred to as stage IV breast cancer due to their severity and high rate of mortality. The median survival time of patients with metastatic BC is reduced to 3 years. Currently, the treatment regimens for metastatic BC are similar to the primary cancer therapeutics and are limited to conventional chemotherapy, immunotherapy, radiotherapy, and surgery. However, metastatic BC shows organ-specific complex tumor cell heterogeneity, plasticity, and a distinct tumor microenvironment, leading to therapeutic failure. This issue can be successfully addressed b

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… The system was further modified using transcytosis-targeting peptide (TTP), where hDOX exhibited enzyme-recovered DNA insertion and selective cytotoxicity to brain metastatic breast cancer cells rather than astrocytes, as well as effective loading into dual-targeting NPs [ 109 ]. hDOX@NPs demonstrated …

Cellular Senescence and the Kidney: Potential Therapeutic Targets and Tools.

Chronic kidney disease (CKD) is an increasing health burden (affecting approximately 13.4% of the population). Currently, no curative treatment options are available and treatment is focused on limiting the disease progression. The accumulation of senescent cells has been implicated in the development of kidney fibrosis by limiting tissue rejuvenation and through the secretion of pro-fibrotic and pro-inflammatory mediators termed as the senescence-associated secretory phenotype. The clearance of senescent cells in aging models results in improved kidney function, which shows promise for the op

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… Interestingly, however, much larger mesoscale nanoparticles of 400 nm were found to selectively target proximal epithelial cells possibly by transcytosis across capillaries and endocytosis into the epithelium ( Williams et al., 2015 ). …

Galectins in the Pathogenesis of Common Retinal Disease.

Diseases of the retina are major causes of visual impairment and blindness in developed countries and, due to an ageing population, their prevalence is continually rising. The lack of effective therapies and the limitations of those currently in use highlight the importance of continued research into the pathogenesis of these diseases. Vascular endothelial growth factor (VEGF) plays a major role in driving vascular dysfunction in retinal disease and has therefore become a key therapeutic target. Recent evidence also points to a potentially similarly important role of galectins, a family of β-g

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… To ensure efficient delivery of nutrients to the underlying neurons, these endothelial cells have developed compound–selective transport systems which consist of luminal and abluminal membrane transport proteins and receptor- and absorptive-mediated transcytosis. …

Advances and prospects in cell therapy for cancer: explorations from T cells to stem cells.

The increasing global burden of cancer necessitates innovative therapeutic strategies. Cell therapy represents a major breakthrough in oncology, evolving rapidly from the successful application of chimeric antigen receptor T (CAR-T) cells in hematologic malignancies to a multiplatform landscape characterized by the concurrent development of diverse strategies. Current research focuses on T cell receptor-engineered T (TCR-T) cells, tumor-infiltrating lymphocytes (TILs), gamma delta (γδ) T cells, CAR-natural killer (CAR-NK) cells, CAR-macrophages (CAR-Ms), and various strategies based on dendrit

Antibody-based drug delivery systems for cancer therapy: Mechanisms, challenges, and prospects.

In recent years, antibody-based cancer therapy has emerged as one of the efficient therapeutic strategies, such as immune checkpoint inhibitors (ICIs), angiogenesis inhibitors, antibody-drug conjugates (ADCs), multi-specific antibodies, and chimeric antigen receptor T (CAR-T) cells, among others. To date, various drug delivery platforms have been developed to improve the bioavailability, delivery convenience, and reduced toxicity towards increased therapeutic efficacy of antibodies. Herein, we emphasize the clinical manifestations of various antibody-based tumor therapies, highlighting their m

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… Figure 11 Schematic illustration of Annexin A1 antibody activated trans-endothelial transcytosis to augment nanomedicine extravasation and the efficacy of cancer immunotherapy by synergistic modulation of the tumor microenvironment. …

Developing Actively Targeted Nanoparticles to Fight Cancer: Focus on Italian Research.

Active targeting is a valuable and promising approach with which to enhance the therapeutic efficacy of nanodelivery systems, and the development of tumor-targeted nanoparticles has therefore attracted much research attention. In this field, the research carried out in Italian Pharmaceutical Technology academic groups has been focused on the development of actively targeted nanosystems using a multidisciplinary approach. To highlight these efforts, this review reports a thorough description of the last 10 years of Italian research results on the development of actively targeted nanoparticles t

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… The Tf approach has been most thoroughly investigated for drug delivery to the brain, as the Tf ligand facilitates transcytosis of the conjugated drug-carrier systems across the blood brain barrier (BBB). …

Cannabidiol on the Path from the Lab to the Cancer Patient: Opportunities and Challenges.

Cannabidiol (CBD), a major non-psychotropic component of cannabis, is receiving growing attention as a potential anticancer agent. CBD suppresses the development of cancer in both in vitro (cancer cell culture) and in vivo (xenografts in immunodeficient mice) models. For critical evaluation of the advances of CBD on its path from laboratory research to practical application, in this review, we wish to call the attention of scientists and clinicians to the following issues: (a) the biological effects of CBD in cancer and healthy cells; (b) the anticancer effects of CBD in animal models and clin

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… After the brain endothelium transcytosis, these particles were expected to target glioma cells overexpressing CB1/2 receptors. As far as CBD was reported to be cytotoxic for glioma, lipid nanoparticles were loaded with CBD and tested as prolonged-release carriers for glioma therapy [ 166 , 167 ]. …

Potential Targeting Mechanisms for Bone-Directed Therapies.

Bone development is characterized by complex regulation mechanisms, including signal transduction and transcription factor-related pathways, glycobiological processes, cellular interactions, transportation mechanisms, and, importantly, chemical formation resulting from hydroxyapatite. Any abnormal regulation in the bone development processes causes skeletal system-related problems. To some extent, the avascularity of cartilage and bone makes drug delivery more challenging than that of soft tissues. Recent studies have implemented many novel bone-targeting approaches to overcome drawbacks. Howe

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… For example, the delivery of anti-β-secretase (BACE1) or iduronate-2-sulfatase (IDS) into the central nervous system surrounded by the blood–brain barrier has been successfully implemented through transferrin receptor-mediated transcytosis. …

Cyclic Peptides in Modern Drug Discovery: Trends and Therapeutic Directions.

Peptide therapeutics are an important drug modality due to their high specificity, favorable safety, and expanding design potential. Among them, cyclic peptides occupy a space between small molecules and biologics, offering improved rigidity, stability, and target engagement. This report analyzes trends in cyclic peptide research using data from the CAS Content Collection over the past two decades. Results show a steady rise in academic publications and patents, reflecting growing interest across discovery and development. Notably, oral administration is gaining attention, indicating progress

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… Additionally, designing cyclic peptides for active transport via peptide transporters (PepT1, PepT2) or exploiting transcytosis pathways can significantly improve oral bioavailability. …

Immunological Targets in Generalized Myasthenia Gravis Treatment: Where Are We Going Now?

BackgroundGeneralized myasthenia gravis (gMG) is a heterogeneous autoimmune disorder marked by antibody-mediated disruption of neuromuscular transmission. Despite advancements in immunosuppressive therapies and biologics, a subset of patients remains refractory, necessitating more targeted and personalized treatment strategies.ObjectiveThis review aims to synthesize current knowledge of the immunopathological mechanisms across gMG subtypes and to explore emerging therapeutic targets tailored to these diverse disease phenotypes.MethodsA narrative review was conducted, integrating recent finding

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… FcRn facilitates the transcytosis of IgG (and albumin) across endothelial cells, thereby markedly extending their half-life. However, a consequence of this mechanism is the prolonged persistence of pathogenic autoantibodies in IgG-mediated autoimmune disorders. …

Mechanisms of Action of the New Antibodies in Use in Multiple Myeloma.

Monoclonal antibodies (mAbs) directed against antigen-specific of multiple myeloma (MM) cells have Fc-dependent immune effector mechanisms, such as complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC), and antibody-dependent cellular phagocytosis (ADCP), but the choice of the antigen is crucial for the development of effective immuno-therapy in MM. Recently new immunotherapeutic options in MM patients have been developed against different myeloma-related antigens as drug conjugate-antibody, bispecific T-cell engagers (BiTEs) and chimeric antigen receptor (CA

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… There are two major factors which could affect pharmacokinetics ( 191 ) of bsAbs immunotherapy: i) the binding to FcRn (neonatal Fc receptor), which in turn mediates the long half-life of IgG molecules in vivo and it is involved in transcytosis from the vascular space out into tissue compartments; ii …

Current advance of nanotechnology in diagnosis and treatment for malignant tumors.

Cancer remains a significant risk to human health. Nanomedicine is a new multidisciplinary field that is garnering a lot of interest and investigation. Nanomedicine shows great potential for cancer diagnosis and treatment. Specifically engineered nanoparticles can be employed as contrast agents in cancer diagnostics to enable high sensitivity and high-resolution tumor detection by imaging examinations. Novel approaches for tumor labeling and detection are also made possible by the use of nanoprobes and nanobiosensors. The achievement of targeted medication delivery in cancer therapy can be acc

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… Butyrate, a multifunctional ligand, was found to facilitate transcytosis by interacting with monocarboxylate transporter 1 (MCT-1), which was found to be highly expressed on the surface of hepatocellular carcinoma (HCC) cells. 390 Nanotechnology can effectively overcome the problems of low bioavailability …

Harnessing CAR-Extracellular Vesicles for Next-Generation Cancer Immunotherapy.

Cancer immunotherapy has experienced substantial progress in recent years, particularly with the advancement of chimeric antigen receptor (CAR) technology, which enables immune cells to selectively target tumor-associated antigens. CARs, now in their fifth generation, are engineered by combining monoclonal antibody fragments with signaling and co-stimulatory domains and have been successfully applied to T cell, natural killer (NK) cell, and macrophage-based therapies. Notable clinical successes, such as tisagenlecleucel and lisocabtagene maraleucel underscore the therapeutic potential of CAR-T

A comprehensive overview on antibody-drug conjugates: from the conceptualization to cancer therapy.

Antibody-Drug Conjugates (ADCs) represent an innovative class of potent anti-cancer compounds that are widely used in the treatment of hematologic malignancies and solid tumors. Unlike conventional chemotherapeutic drug-based therapies, that are mainly associated with modest specificity and therapeutic benefit, the three key components that form an ADC (a monoclonal antibody bound to a cytotoxic drug via a chemical linker moiety) achieve remarkable improvement in terms of targeted killing of cancer cells and, while sparing healthy tissues, a reduction in systemic side effects caused by off-tum

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… Therefore, this FcRn-mediated transcytosis into the extracellular space, although involving only a small percentage of the internalized ADC -complex, can potentially enhance the clearance of ADC and thus reduce its therapeutic index ( Xu, 2015 ). …

Exploring the dual role of B cells in solid tumors: implications for head and neck squamous cell carcinoma.

In the tumor milieu of head and neck squamous cell carcinoma (HNSCC), distinct B cell subpopulations are present, which exert either pro- or anti-tumor activities. Multiple factors, including hypoxia, cytokines, interactions with tumor cells, and other immune infiltrating lymphocytes (TILs), alter the equilibrium between the dual roles of B cells leading to cancerogenesis. Certain B cell subsets in the tumor microenvironment (TME) exhibit immunosuppressive function. These cells are known as regulatory B (Breg) cells. Breg cells suppress immune responses by secreting a series of immunosuppressi

"Bioinspired" Membrane-Coated Nanosystems in Cancer Theranostics: A Comprehensive Review.

Achieving precise cancer theranostics necessitates the rational design of smart nanosystems that ensure high biological safety and minimize non-specific interactions with normal tissues. In this regard, "bioinspired" membrane-coated nanosystems have emerged as a promising approach, providing a versatile platform for the development of next-generation smart nanosystems. This review article presents an in-depth investigation into the potential of these nanosystems for targeted cancer theranostics, encompassing key aspects such as cell membrane sources, isolation techniques, nanoparticle core sel