Targeting triple negative breast cancer stem cells using nanocarriers

Discover Nano, Journal Year: 2024, Volume and Issue: 19(1)

Published: March 7, 2024

Abstract Breast cancer is a complex and heterogeneous disease, encompassing various subtypes characterized by distinct molecular features, clinical behaviors, treatment responses. Categorization of based on the presence or absence estrogen receptor (ER), progesterone (PR), human epidermal growth factor 2 (HER2), leading to such as luminal A, B, HER2-positive, triple-negative breast (TNBC). TNBC, comprising around 20% all cancers, lacks expression ER, PR, HER2 receptors, rendering it unresponsive targeted therapies presenting significant challenges in treatment. TNBC associated with aggressive behavior, high rates recurrence, resistance chemotherapy. Tumor initiation, progression, are attributed stem cells (BCSCs), which possess self-renewal, differentiation, tumorigenic potential. Surface markers, self-renewal pathways (Notch, Wnt, Hedgehog signaling), apoptotic protein (Bcl-2), angiogenesis inhibition (VEGF inhibitors), immune modulation (cytokines, checkpoint inhibitors) among key targets discussed this review. However, targeting BCSC subpopulation presents challenges, including off-target effects, low solubility, bioavailability anti-BCSC agents. Nanoparticle-based offer promising approach target cellular processes implicated survival BSCS TNBC. In review, we explore nanocarrier-based approaches for BCSCs aiming overcome these improve outcomes patients. These nanoparticle-based therapeutic strategies hold promise addressing gap delivering while minimizing systemic toxicity enhancing efficacy. Graphical abstract

Language: Английский

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Multiplexed Lectin-PAINT super-resolution microscopy enables cell glycotyping

Communications Biology, Journal Year: 2025, Volume and Issue: 8(1)

Published: Feb. 20, 2025

Glycosylation profoundly influences cellular function, yet deciphering its intricate patterns remains a formidable challenge. Current techniques often compromise sensitivity, multiplexing, or the ability to capture in-situ cell-to-cell variations. To address these limitations, we introduce 'Lectin-PAINT,' super-resolution imaging method enabling multiplexed live-cell visualization of glycocalyx at single-cell and single-molecule levels. Lectin-PAINT leverages reversible binding lectins specific carbohydrate families perform point accumulation in nanoscale topography (PAINT), identification, mapping, tracking carbohydrates with resolution beyond diffraction limit. Our technique harnesses tailored lectin library, spanning key recognition, offering insights into their abundance, affinity, mobility. Through 8-color imaging, extract more than 350 glycosylation parameters resolution, creating cell's 'glycotype' glycan fingerprint. We showcase power this approach by glycotyping categorizing diverse set cancer cell types, shedding light on heterogeneity variability cancer. In future, research will contribute fundamental understanding changes due disease.

Language: Английский

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Green synthesis of chitosan/silver nanocomposite using kaempferol for triple negative breast cancer therapy and antibacterial activity

Environmental Research, Journal Year: 2023, Volume and Issue: 238, P. 117109 - 117109

Published: Sept. 9, 2023

Language: Английский

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GlycoPro: A High-Throughput Sample-Processing Platform for Multi-Glycosylation-Omics Analysis

Engineering, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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Crafting a Molecular Trojan Horse: Sialic Acid-Modified PLGA Nanoparticles for Targeted Lung Cancer Therapy

Molecular Pharmaceutics, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 28, 2025

The glycan receptors prominently expressed on the surface of lung cancer cells offers promising targets for drug delivery. prepared gemcitabine (GB)-loaded PLGA-NPs and sialic acid (Siac)-modified exhibited a uniform polydispersity index (PDI) value below 0.3, particle size under 200 nm, negative zeta potentials ranging from −17.45 to −21.45 mV. Entrapment efficiency (% EE) loading values exceeded 70% 8%, respectively. SEM TEM showed that particles were uniformly dispersed with spherical shape. FTIR, XRD, TGA, DSC analyses indicated physiochemical stability within nanoformulations. Controlled (26.92 31.64% 24 h at pH 7.4) pH-sensitive (36.80 40.25% 5.5) GB release observed different formulations PLGA-NPs. MTT cytotoxicity assay revealed IC50 control, GB-PLGA-NPs, GB-PLGA-Siac-NPs as 13.65 ± 1.20, 8.14 1.24, 4.16 1.05 μg/mL, Co6-GB-PLGA-Siac-NPs significantly higher cellular uptake than Co6-GB control (p < 0.001) Co6-GB-PLGA-NPs 0.01) Pharmacokinetic profiles AUC (ng·h/mL) (8355.07 2006.45) compared GB-PLGA-NPs (6145.58 969.25) (1510.72 81.08), resulting in bioavailability GB-PLGA-Siac-NPs. Biodistribution studies confirmed superior localization DiD-GB-PLGA-Siac-NPs, by radiant signal B[a]P induced cancerous tissues relative DiD-GB-PLGA-NPs after 1 0.001), 4 0.01), 12 which could be attributed their ability target glycans. In vivo anticancer efficacy B[a]P-induced mice model depicted effectively inhibited reduced systemic toxicity, evidenced average number cells, body weight values, survival analysis, biochemical parameters associated organs (such liver kidney), histopathological analysis. Therefore, GB-loaded Siac-coated PLGA nanoparticles serve an efficient vehicle delivery via targeting therapy.

Language: Английский

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Harnessing the Bishomolithocholic Acid Scaffold for Selective Sialyltransferase Inhibition: A Targeted Approach to Suppress Breast Cancer Metastasis

European Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: 292, P. 117674 - 117674

Published: April 24, 2025

Language: Английский

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Nanomaterials for delivery of drugs and genes to disrupt notch signaling pathway in breast cancer

Naunyn-Schmiedeberg s Archives of Pharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: May 20, 2025

Language: Английский

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Phenyl boronic acid conjugated lipid nanoparticles for targeted delivery of gamma-secretase inhibitor to breast cancer cells

Drug Development and Industrial Pharmacy, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 19

Published: May 23, 2025

The major objective of the present study is to develop and evaluate phenyl boronic acid (PBA) conjugated solid lipid nanoparticles (PBA-SUL@SLN) for targeted delivery sulindac (SUL) breast cancer (BC) cells.Significance: Utilizing a dual approach that combines PBA-mediated targeting with Notch-1 pathway inhibition by SUL, aims enhance therapeutic selectivity efficacy against an aggressive BC subtype, triple negative (TNBC), which lacks well defined molecular targets. PBA-SUL@SLN formulation was prepared using emulsification-solvent evaporation method analysed particle size, zeta potential, entrapment efficiency, pH sensitive drug release. Cellular uptake studies were conducted examine selective internalization in TNBC cells. assessed evaluating Notch-1expression modulation epithelial-to-mesenchymal transition (EMT), stem cell (CSC) activity, cytotoxic effects compared normal exhibited optimal size (153.35 nm), potential (22.87 mV), efficiency 83.06%, preferential release observed acidic tumor microenvironment. Increased cellular MDA-MB-231 cells led notable downregulation Notch-1, reduction CSC activity. Cytotoxicity assays revealed strong while causing minimal on presents promising strategy TNBC, addressing key limitations existing treatments.

Language: Английский

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Dual TTK/PLK1 inhibition has potent anticancer activity in TNBC as monotherapy and in combination

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: Aug. 9, 2024

Background Threonine tyrosine kinase (TTK) and polo-like 1 (PLK1) are common essential kinases that collaborate in activating the spindle assembly checkpoint (SAC) at kinetochore, ensuring appropriate chromosome alignment segregation prior to mitotic exit. Targeting of either TTK or PLK1 has been clinically evaluated cancer patients; however, dual inhibitors have not yet pursued. Here we present vitro vivo characterization a first class, TTK/PLK1 inhibitor (BAL0891). Methods Mechanism action studies utilized biochemical proteomics-based target-engagement assays. Cellular end-point assays included immunoblot- flow cytometry-based cell cycle analyses SAC integrity evaluation using immunoprecipitation immunofluorescence approaches. Anticancer activity was assessed growth efficacy evaluated, alone combination with paclitaxel carboplatin, mouse models triple negative breast (TNBC). Results BAL0891 elicits prolonged effect on TTK, transient PLK1. This unique profile potentiates disruption, forcing tumor cells aberrantly exit mitosis faster kinetics than observed TTK-specific inhibitor. Broad anti-proliferative demonstrated across solid lines . Moreover, intermittent intravenous single-agent treatment MDA-MB-231 model TNBC induced profound regressions associated in-tumor target occupancy. Furthermore, differential responses panel thirteen patient-derived xenograft indicated anticancer subset (~40%). Using flexible dosing approach, pathologically confirmed cures were paclitaxel, whereas synergy carboplatin schedule dependent. Conclusions Dual inhibition represents novel approach for human cancer, including patients, potential potent favorable therapeutic index. approaches may provide an avenue expand responsive patient populations.

Language: Английский

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TARGETING ANGIOGENESIS WITH FLUPHENAZINE-ZINC OXIDE NANOCONJUGATES: A POTENTIAL MECHANISM FOR IMPROVING ANTIPSYCHOTIC EFFICACY

International Journal of Applied Pharmaceutics, Journal Year: 2023, Volume and Issue: unknown, P. 339 - 343

Published: Sept. 7, 2023

Objective: This study aimed to develop a more effective formulation of Fluphenazine (FLP) for the management psychosis. Antipsychotics are widely used treatment severe mental disorders such as schizophrenia and bipolar disorder. However, their clinical use is limited due various side effects low efficacy in large number patients. Nanoparticle-based drug delivery systems have shown great potential improving pharmacokinetics pharmacodynamics drugs, including antipsychotics. Zinc oxide nanoparticles (ZnO NPs) emerged promising carrier unique physicochemical properties, biocompatibility, toxicity. Methods: In this study, we reported preparation characterization FLU-encapsulated ZnO NPs (FLU-ZnO-NPs) The synthesized FLU-ZnO-NPs were characterized using techniques, X-Ray Diffractometer, Energy Dispersive analysis, Transmission Electron Microscopy, Zetasizer (Malvern). Results: results showed that had improved solubility, enhanced bioavailability, targeted delivery, reduced Conclusion: development could provide safe option patients with disorders.

Language: Английский

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