Stimuli-responsive graphene oxide and methotrexate-loaded magnetic nanoparticles for breast cancer-targeted therapy.

Aim: Nanocomposites of graphene oxide (GO) loaded with PEGylated superparamagnetic iron oxide nanoparticles and grafted with methotrexate and stimuli-responsive linkers (GO-SPION-MTX) were developed for photothermal and chemotherapy of breast cancer. Methods: PEGylated SPIONs were synthesized and conjugated with chemotherapeutic targeting agent MTX, which were then loaded on GO to prepare GO-SPION-MTX nanocomposites. To evaluate the photothermal effect of the nanocomposites, they were examined in breast cancer cell lines with low doses of near-infrared (NIR) laser radiation with/without acetazolamide. Results: The GO-SPION-MTX nanocomposites were found to be internalized by the folate-receptor-positive cancer cells and induce high cytotoxicity on exposure to NIR laser rays. Conclusion: Our findings suggest that the GO-SPION-MTX nanocomposite can potentially be used as a multimodal nanomedicine/theranostic against breast cancer.

Folate receptor-mediated delivery of 1-MDT-loaded mesoporous silica magnetic nanoparticles to target breast cancer cells.

Aims: The efficiency of mesoporous silica magnetic nanoparticles (MSMNP) as a targeted drug-delivery system was investigated. Methods: The superparamagnetic iron oxide nanoparticles (NP) were synthesized, coated with mesoporous silica and conjugated with polyethylene glycol and methotrexate. Next, 1-methyl-D-tryptophan was loaded into the prepared nanosystems (NS). They were characterized using transmission electron microscopy, scanning electron microscopy, dynamic light scattering, vibrating sample magnetometer, x-ray powder diffraction, Fourier transform-infrared spectroscopy and the Brunauer-Emmett-Teller method and their biological impacts on breast cancer cells were evaluated. Results: The prepared NSs displayed suitable properties and showed enhanced internalization by folate-receptor-expressing cells, exerting efficient cytotoxicity, which was further enhanced by the near-infrared radiation irradiation. Conclusion: On the basis of our findings, the engineered NS is a promising multifunctional nanomedicine/theranostic for solid tumors.

Targeted combined therapy in 2D and 3D cultured MCF-7 cells using metformin and erlotinib-loaded mesoporous silica magnetic nanoparticles.

AIM: This research aims to develop potential therapeutic nanostructures (NSs) encapsulating metformin (MET) and erlotinib (ER) for combinational therapy in breast cancer. METHODS: The ER and MET, both were loaded on mesoporous silica magnetic nanoparticles conjugated with polyethylene glycol and methotrexate to achieve targeted NSs. The developed NSs were characterised using SEM, DLS, and FTIR. Afterward, MTT, Trypan blue, and DNA extraction assays were operated for biological evaluations in the 2D and 3D MCF-7 cells. RESULTS: Physicochemical approaches indicated the mean diameter of 69.4 nm ± 9.5 (PDI = 0.64), and neutral charge (2 mv) for the developed NSs. MET and ER-loaded NSs exhibited 62.56% ± 4.41 and 67.73% ± 3.03 drug release amount in pH = 5.4, respectively. MTT assay revealed that ER- and MET-loaded NSs had less metabolic activity (≈ 20%) in comparison with non-targeted NSs. CONCLUSION: Overall, our combined ER and MET-loaded targeted NSs result in a synergistic inhibitory impact on MCF-7 cells.

Recent advances in breast cancer immunotherapy: The promising impact of nanomedicines.

Breast cancer (BC) is one of the prevalent cancers among women. Generally, the treatment of BC is mostly based on several prominent strategies, including chemotherapy, surgery, endocrine therapy, molecular targeted therapy, and radiation. Owing to the growing knowledge about the complexity of BC pathobiology, immunotherapy as a promising treatment modality has substantially improved the patients' care in the clinic. Immunotherapy is used to harness the patient's immune system to recognize and battle devious cancer cells. As a novel therapy approach, this emerging strategy targets the key molecular entities of tumor tissue. To achieve maximal therapeutic impacts, the dynamic interplay between cancer and immune cells needs to be fully comprehended. The key molecular machinery of solid tumors can be targeted by nanoscale immunomedicines. While discussing the potential biomarkers involved in the initiation and progression of BC, we aimed to provide comprehensive insights into the immunotherapy and articulate the recent advances in terms of the therapeutic strategies used to control this disease, including immune checkpoint inhibitors, vaccines, chimeric antigen receptor T cells therapy, and nanomedicines.

Graphene-based multifunctional nanosystems for simultaneous detection and treatment of breast cancer.

Breast cancer is one of the most life-threatening malignancies with high mortality among women. Chemotherapy, radiotherapy, surgical operation, and combination therapy are commonly applied modalities in breast cancer therapy. However, the full treatment of the disease is often failed because of the formation of a permissive milieu, so-called tumor microenvironment (TME). In such a setting, immunosurveillance is impaired and high-pressure tumor interstitial fluid resists drug penetration due to the creation of irregular tumor microvasculature, the initiation of drug resistance mechanisms, the emergence of undesired side effects, and relapse of the disease even after a vigorous treatment. To tackle these pitfalls, smart multifunctional nanosystems (NSs) have been developed based on passive and active targeting mechanisms. Of various NSs, graphene-based nanosystems (GrNSs) offer unique physicochemical features, including functionalization with various targeting and imaging ligands, offering photothermal and photodynamic therapy (PTT and PDT) potentials combined with chemotherapy of the loaded drugs. Multimodal GrNSs, to be transformed into precision medicine, demand rationalized preclinical and clinical studies to examine their pharmacokinetics and pharmacodynamics (PD) properties together with their behaviors in TME. For a successful transformation towards personalized nanomedicine, furthermore, key pivotal patient- and formulation-oriented challenges (e.g., patients' genomic/proteomic profiles and PK/PD properties) must be addressed before any clinical interventions. This review provides comprehensive insights into the smart GrNSs and discusses their applications for the concurrent diagnosis and treatment of solid tumors.

Renewed interests in carbonic anhydrase IX in relevance to breast cancer treatment.

The highly proliferating cancerous cells can form permissive accommodating milieu - the so-called tumor microenvironment (TME). During the initiation of solid tumors, hypoxia plays a key role in glycolysis, which can trigger the anomalous overexpression of several enzymes and transporters involved in the metabolism of glucose. Of these, carbonic anhydrases (CAs), especially CAIX, together with other molecular machinery involved in the production/trafficking of acidic byproducts, play key roles in the regulation of intracellular and extracellular pH. CAIX, along with other molecular machinery of cancer cells such as Na+/H+ exchanger 1 (NHE1) and V-type H+-ATPase (V-ATPase), alkalinizes the tumor cells and maintains the acidic pH condition within the extracellular fluid of the TME. It facilitates the progression and metastasis of cancer and intensifies the migration and invasion of cancer cells. Thus, inhibition of CAIX can be considered a highly effective and promising therapeutic strategy in the treatment of aggressive tumors.

Preventive Effect of Atorvastatin (80 mg) on Contrast-Induced Nephropathy After Angiography in High-Risk Patients: Double-Blind Randomized Clinical Trial.

BACKGROUND: Contrast-induced nephropathy (CIN) is one of the most important complications of angiography in patients with chronic kidney disease (CKD) or diabetes mellitus. The prevention of CIN can decrease therapeutic costs and hospital stays. There is controversy in the literature over the preventive effect of statins on CIN. OBJECTIVES: This study was designed to evaluate the preventive effect of atorvastatin on CIN after angiography in CKD and diabetic patients. PATIENTS AND METHODS: In this placebo-controlled, double-blind clinical trial, patients with diabetes mellitus or CKD (15 < GFR < 60 mL/min, Cr > 1.5 mg/dL) and an age range of 55 - 75 years candidated for angiography were included. The patients were randomized to 2 groups: one group receiving atorvastatin (80 mg/d from 48 h before angiography) and the other one receiving a placebo. All the patients received intravenous isotonic saline and N-acetylcysteine. CIN was defined as an increase in serum creatinine more than 0.5 mg/dL or more than 25% from the baseline values. RESULTS: Totally, 220 patients at a mean age of 63.85 ± 8.89 years and a mean body mass index of 31.41 ± 5.99 kg/m(2) were evaluated. In comparison of before-after values, there was a significant increase in serum creatinine in the placebo group (P = 0.000). The incidence of CIN was significantly higher in the control group 24 hours after angiography (P = 0.010); however, at a 48-hour interval, there was no significant difference in CIN between the 2 groups. CONCLUSIONS: Standard hydration and N-acetylcysteine and atorvastatin (80 mg) reduced the incidence of CIN, and this regimen was more effective than was the regimen of hydration and N-acetylcysteine (without atorvastatin) in decreasing CIN. Accordingly, it is reasonable to prescribe atorvastatin before angiography in high-risk patients.