Molecular Biology Reports, Год журнала: 2024, Номер 51(1)
Опубликована: Окт. 17, 2024
Язык: Английский
Journal of Drug Delivery Science and Technology, Год журнала: 2024, Номер 93, С. 105401 - 105401
Опубликована: Янв. 25, 2024
Cancer is a major public health concern worldwide; it the second-highest cause of death in United States. According to projections cancer incidence and mortality rates throughout world for year 2023, triple-negative breast (TNBC) expected be leading related among women worldwide. Traditional strategies treatment TNBC have many drawbacks, such as drug resistance, toxicity etc. Discovering novel delivery techniques researching innovative, efficient methods important. This review discusses types subtypes TNBC. The problems associated with standard therapies, mechanism resistance highlights need develop therapeutic strategies. It provides information on relative prevalence severity cancer. Several approaches viz. targeted therapy, gene bacterial-mediated nanomedicine, immune checkpoint inhibitors, theranostic, radiotherapy, chemotherapy, immunotherapy, herbal AI-based TNBC, are discussed detail. Additionally, diagnostic techniques, including imaging biopsy, expression profiling, mammography, magnetic resonance imaging, ultrasound, computed tomography scan, positron emission immunohistochemistry, been effective treatment. in-depth analysis innovative individualized care serve patients better.
Язык: Английский
Процитировано
19
Discover Nano, Год журнала: 2024, Номер 19(1)
Опубликована: Март 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
Язык: Английский
Процитировано
17
Scientific Reports, Год журнала: 2025, Номер 15(1)
Опубликована: Фев. 19, 2025
Triple-negative breast cancer (TNBC) presents a global health challenge due to its aggressive behavior and limited treatment options. This study explores novel therapeutic strategy using C-peptide-conjugated solid lipid nanoparticles (C-peptide-SLNs) for targeting paclitaxel (PTX) delivery in TNBC treatment. C-peptide, derived from endostatin, enhances efficacy by overexpressed integrin αvβ3 receptors on cells. Characterization confirmed suitable particle size, stability, encapsulation efficiency over 90%, with favorable release profiles acidic tumor environments. In vitro, C-peptide-SLN-PTX markedly improved cytotoxicity against 4T1 carcinoma cells, an IC50 of 1.2 µg/mL, compared 3.4 µg/mL SLN-PTX 8.9 free PTX. Wound-healing assays verified significant inhibition cell migration MDA-MB-231 lines. Flow cytometry αv C-peptide-SLN-PTX. vivo studies tumor-bearing mice showed 82% volume reduction prevented pulmonary metastasis, normal liver enzyme levels indicating reduced toxicity. PET imaging revealed decreased metabolic activity treated groups, immunohistochemical analyses demonstrated superior antitumor Ki-67 expression apoptosis induction (p53 upregulation, Bcl-2 downregulation). These findings highlight the potential C-peptide-SLNs as effective targeted PTX system TNBC, offering promising avenues enhancing strategies.
Язык: Английский
Процитировано
3
IUBMB Life, Год журнала: 2025, Номер 77(1)
Опубликована: Янв. 1, 2025
Targeting the influencing factors in tumor growth and expansion microenvironment is one of key approaches to cancer immunotherapy. Various can cooperation stimulate growth, suppress anti-tumor immune responses, promote drug resistance, ultimately enhance recurrence. Therefore, due dependence close these axes, their combined targeting have a greater effect compared individual targeting. Among important affecting region, CD73 EGFR play an role by stimulating each other's expression function. we intended use nanocarriers that had previously produced characterized deliver anti-CD73 siRNAs murine breast 4T1 cells. Silencing could significantly induce cell death Downregulation CD73/EGFR axis also suppressed migratory proliferative potential This therapeutic strategy inhibited ovo model. These findings imply simultaneous be considered novel immunotherapeutic approach needs further investigation future studies.
Язык: Английский
Процитировано
2
Clinical & Translational Oncology, Год журнала: 2024, Номер unknown
Опубликована: Авг. 18, 2024
Язык: Английский
Процитировано
9
Cell Communication and Signaling, Год журнала: 2025, Номер 23(1)
Опубликована: Янв. 13, 2025
The Golgi apparatus is widely considered a secretory center and hub for different signaling pathways. Abnormalities in dynamics can perturb the tumor microenvironment influence cell migration. Therefore, unraveling regulatory network of searching pharmacological targets would facilitate development novel anticancer therapies. Previously, we reported an unconventional role tethering factor golgin-97 inhibiting breast motility, its downregulation was associated with poor patient prognosis. However, specific mechanism cancer progression vivo remain unclear. We integrated genetic knockout (KO) golgin-97, animal models (zebrafish xenograft mice), multi-omics analysis (next-generation sequencing proteomics), bioinformatics analysis, kinase inhibitor treatment to evaluate effects KO triple-negative cells. Gene knockdown followed by qRT‒PCR, Western blotting, viability, migration, cytotoxicity assays were performed elucidate mechanisms KO-mediated invasion. A mouse model used investigate drug therapy. demonstrated that promoted metastasis zebrafish models. Multi-omics revealed Wnt pathway, MAPK cascades, inflammatory cytokines are involved KO-induced progression. Targeting ERK1/2 p38 pathways effectively attenuated golgin-97-induced reduced expression mediators, enhanced chemotherapeutic effect paclitaxel vitro vivo. Specifically, compared regimen, combination inhibitors significantly prevented lung injury. further hypoxia physiological condition reduces cancer, revealing potential feedback loop between ERK/MAPK golgin-97. Our results collectively support microenvironment, possibly providing new insights anti-breast development.
Язык: Английский
Процитировано
1
Journal of Nanobiotechnology, Год журнала: 2025, Номер 23(1)
Опубликована: Март 22, 2025
Triple-negative breast cancer (TNBC) is a highly aggressive subtype of characterized by an extremely poor prognosis. Photoimmunotherapy has emerged as promising strategy for the treatment TNBC. This approach works selectively destroying tumor cells, releasing tumor-associated antigens, activating immune system, and effectively inhibiting proliferation metastasis. However, majority current phototheranostic approaches are hindered limited tissue penetration in first near-infrared (NIR-I) ultraviolet–visible (UV–Vis) regions. Additionally, due to lack specific subcellular targets, it may be difficult treat deep-seated lesions with ambiguous extensive boundaries caused TNBC metastases. Consequently, development effective, deep-penetrating, organelle-targeted phototheranostics essential enhancing outcomes work proposes novel molecular design NIR-II realize planar rigid conjugation alkyl chain functionalization. The di-hexaalkyl chains vertical configuration on donor (4H-cyclopenta[2,1-b:3,4-b'] dithiophene) shielding units (fluorene) introduced construct S-D-A-D-S type (IR-FCD). structure IR-FCD exhibits robust intramolecular charge transfer capability, lower band gap, enhanced photon absorption properties, significant steric hindrance from vertically arranged minimize non-radiative energy loss. By incorporating N-(but-3-yn-1-yl)-4-methylbenzenesulfonamide at terminus elongated chain, followed self-assembly into DSPE-S-S-PEG2000, excitable (IR-FCD-Ts NPs) endoplasmic reticulum (ER) targeting capability were successfully synthesized imaging-guided photoimmunotherapy IR-FCD-Ts NPs demonstrate exceptional optical characteristics, maximum 1068 nm (extending 1300 nm) emission 1273 1700 nm), along high molar coefficient 2.76*104 L/mol·c 1064 aqueous solution. Under exposure laser irradiation, exhibit superior photothermal properties have potential photodynamic therapy. ER, thereby inducing ER stress significantly immunogenic cell death (ICD) triggers strong antitumor response inhibits metastasis
Язык: Английский
Процитировано
1
ACS Omega, Год журнала: 2024, Номер 9(2), С. 2615 - 2628
Опубликована: Янв. 4, 2024
Glioblastoma (GBM) is the most aggressive and fatal brain tumor, with approximately 10,000 people diagnosed every year in United States alone. The typical survival period for individuals glioblastoma ranges from 12 to 18 months, significant recurrence rates. Common therapeutic modalities tumors are chemotherapy radiotherapy. main challenges treatment of high toxicity, poor selectivity, limited accumulation anticancer agents as a result presence blood–brain barrier. To overcome these challenges, researchers have explored strategies involving combination targeting peptides possessing specific affinity overexpressed cell-surface receptors conventional via prodrug approach. This approach results creation peptide drug conjugates (PDCs), which facilitate traversal across barrier (BBB), enable preferential within neoplastic microenvironment, selectively target cancerous cells. increases tumors, thereby improving efficiency minimizing toxicity. Leveraging HAIYPRH (T7) transferrin receptor (TfR) on glioma cells, novel T7-SN-38 conjugate was developed. demonstrates about 2-fold reduction glide score (binding affinity) compared T7 while maintaining comparable orientation TfR site using Schrödinger-2022–3 Maestro 13.3 ligand preparation Glide SP-Peptide docking. Additionally, SN-38 extends into solvent-accessible region, enhancing its susceptibility protease hydrolysis at cathepsin B (Cat B) cleavable site. SN-38-ether-peptide displayed stability buffer physiological pH, cleavage release free cytotoxic observed exogenous B. synthesized exhibited potent activities cellular models vitro. In addition, blocking resulted notable inhibition cytotoxicity conjugate, reversed when added work potential targeted delivery receptor-targeted conjugate.
Язык: Английский
Процитировано
7
Medicine, Год журнала: 2024, Номер 103(8), С. e37264 - e37264
Опубликована: Фев. 23, 2024
This study aimed to use bioinformatics approaches for predicting the anticancer mechanisms of curcumin on triple-negative breast cancer (TNBC) and verify these predictions through in vitro experiments. Initially, Cell Counting Kit-8 (CCK8) assay was employed rigorously investigate influence proliferative capacity TNBC cells. Subsequently, flow cytometry meticulously assess impact cellular apoptosis cell cycle regulation. Transwell assays were evaluate effect motility RNA sequencing conducted, followed by Gene Ontology Kyoto Encyclopedia Genes Genomes enrichment analyses differentially expressed genes, aiming elucidate potential underlying curcumin's effects. To thoroughly interactions among multiple proteins, we constructed a protein-protein interaction (PPI) network. Finally, expression levels several key including fibronectin, mTOR, β-Catenin, p-Akt, Akt, N-Cadherin, p-S6, S6, assessed using western blot. The CCK8 results showed that significantly inhibited proliferation Hs578T MDA-MB-231 Flow induced cells arrested at G2/M phase. Additionally, effectively reduced Enrichment analysis data mechanism action associated with signaling pathways such as cancer, focal adhesion, PI3K-Akt pathways. network proteins. Western blotting decreased proteins Fibronectin, S6. Curcumin exhibits its therapeutic modulating It may inhibit epithelial-mesenchymal transition process downregulating involved mTOR pathways, thereby suppressing These findings provide experimental evidence considering strategy treatment TNBC.
Язык: Английский
Процитировано
7
International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(6), С. 3354 - 3354
Опубликована: Март 15, 2024
In recent years, newly emerging therapies, such as immune checkpoint inhibitors and antibody-drug conjugates, have further improved outcomes for breast cancer patients. However, recurrent metastatic often eventually develops resistance to these drugs, cure is still rare. As such, the development of new therapies refractory that differ from conventional mechanisms action necessary. Sphingosine-1-phosphate (S1P) a key molecule with variety bioactive activities, including involvement in cell proliferation, invasion, metastasis. S1P also contributes formation microenvironment by inducing surrounding vascular- lymph-angiogenesis regulating system. this article, we outline basic mechanism S1P, summarize previous findings on function cells microenvironment, discuss clinical significance therapeutic potential targeting signaling.
Язык: Английский
Процитировано
6