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    A comparison study between doxorubicin and curcumin co-administration and co-loading in a smart niosomal formulation for MCF-7 breast cancer therapy
    (Elsevier, 2023) Saharkhiz, Shaghayegh; Zarepour, Atefeh; Nasri, Negar; Cordani, Marco; Zarrabi, Ali
    Chemotherapy agents often exhibit limited effectiveness due to their fast elimination from the body and nontargeted delivery. Emerging nanomaterials as drug delivery carriers open new expectancy to overcome these limitations in current chemotherapeutic treatments. In this study, we introduce and evaluate a smart pHresponsive niosomal formulation capable of delivering Doxorubicin (DOX) and Curcumin (CUR) in both individually and co-loaded forms. In particular, drug-loaded niosomes were prepared using thin-film hydration method and then characterized via different physicochemical analyses. The pH responsivity of the carrier was assessed by performing a drug release study in three different pH conditions (4, 6.5, and 7.4). Finally, the anticancer efficacy of the therapeutic compounds was evaluated through the MTT assay. Our results showed spherical particles with a size of about 200 nm and -2 mV surface charge. Encapsulation efficiency (EE%) of the nanocarrier was about 77.06 % and 79.08 % for DOX and CUR, respectively. The release study confirmed the pH responsivity of the carrier. The MTT assay results revealed about 39 % and 43 % of cell deaths after treatment with cur-loaded and dox-loaded niosomes, which increased to 74 % and 79 % after co-administration and coloading forms of drugs, respectively, exhibiting increased anticancer efficacy by selectively delivering DOX and CUR individually or in combination. Overall, these findings suggest that our nanoformulation holds the potential as a targeted and highly effective approach for cancer management and therapy, overcoming the limitations of conventional chemotherapy drugs.
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    Development of pH and thermo-responsive smart niosomal carriers for delivery of gemcitabine to the breast cancer cells
    (Springernature, 2024) Ghalehshahi, Saeid Shirzadi; Saharkhiz, Shaghayegh; Naderi, Nazanin; Nasri, Negar; Saharkhiz, Shiva; Zarepour, Atefeh; Goodarzi, Reza
    The utilization of intelligent drug carriers in cancer therapy has emerged as a transformative paradigm in modern oncology. These advanced drug delivery systems exploit the distinctive characteristics of cancer cells and their surrounding microenvironment to attain precise and targeted drug release at the tumor site. In this study, we aim to introduce a novel niosome formulation endowed with dual-responsive properties, pH, and thermo-sensitivity, to enhance drug release precisely within the intended target site. Therefore, thin-film method was used for the fabrication of niosomes, incorporating dipalmitoylphosphatidylcholine (DPPC), as thermoresponsive phospholipid, and citraconic anhydride, as pH-responsive linker. The fabricated niosomes were evaluated through physicochemical analysis using Fourier-transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), and scanning electron microscopy (SEM). Additionally, the entrapment efficiency (EE%) and drug release pattern of gemcitabine (GEM) were quantified at different conditions using UV-Visible spectroscopy. The bioactivity of these niosomes was also evaluated via cytotoxicity assay and flow cytometry. Results of physicochemical analysis verified the successful fabrication of spherical nanoparticles, with a size range of about 100-150 nm and a neutral surface charge. Furthermore, the fabricated niosomes showed sensitivity to acidic pH (6.5) and temperature exceeding the transition temperature (Tc) of the DPPC (41.5 degrees C). Importantly, the drug release profile indicated about 10-17% enhancement in drug release for the dual-stimuli platform in comparison to the single-stimuli ones. The cytotoxicity assay and flow cytometry analysis demonstrated an approximate 10% increase in cytotoxicity and about a 2.5-fold rise in apoptosis induction for the dual-stimuli responsive platform in contrast to the free drug. In conclusion, this dual-stimuli responsive nanocarrier presents a promising strategy to enhance the specificity and efficacy of cancer chemotherapy while simultaneously reducing the adverse side effects experienced by patients.
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    Empowering Cancer Therapy: Comparing PEGylated and Non-PEGylated Niosomes Loaded with Curcumin and Doxorubicin on MCF-7 Cell Line
    (Mdpi, 2023) Saharkhiz, Shaghayegh; Zarepour, Atefeh; Zarrabi, Ali
    Cancer remains an enduring challenge in modern society, prompting relentless pursuits to confront its complexities. However, resistance often emerges against conventional treatments, driven by their inherent limitations such as adverse effects and limited solubility. Herein, we spotlight a remarkable solution; a niosomal platform engineered to tandemly ferry two potent agents, doxorubicin (DOX) and curcumin (CUR). Notably, we delve into the pivotal role of PEGylation, unraveling its impact on therapeutic efficacy. These niosomes consist of Span 60, Tween 60, and cholesterol with a molar ratio of 5:2:3, which were prepared via a thin film hydration method. The physicochemical characterization of particles was performed using DLS, zeta potential measurement, SEM, and FTIR analysis. In addition, their encapsulation efficiency and release profile were determined using the HPLC method. Finally, their cytotoxicity and biocompatibility effects were checked by performing an MTT assay test on the MCF7 and L929 cell lines. The obtained results confirmed the successful fabrication of co-loaded niosomal structures with and without PEG coating. The fabricated nanoparticles had sizes in the range of 100 to 200 nm with a surface charge of about -18 mV for particles without PEG coating and -40 mV for coated particles. Notably, DOX encapsulation efficiency leaps from 20% to 62% in the transition from uncoated to coated, while CUR exhibits an impressive surge from 80% to 95%. The drug release was more controlled and slower in the coated sample. Finally, the MTT results confirmed the biocompatibility and synergistic effect of the simultaneous use of two drugs on cancer cells in the PEGylated niosomal particle. Based on the results, PEGylated niosomal particles can be considered adept vehicles for the simultaneous delivery of different chemotherapy cargoes with synergic interaction to overcome cancer.
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    A new theranostic pH-responsive niosome formulation for doxorubicin delivery and bio-imaging against breast cancer
    (Elsevier, 2023) Saharkhiz, Shaghayegh; Zarepour, Atefeh; Zarrabi, Ali
    As one of the newest generations of nanoplatforms, smart nanotheranostics have attracted signifivant attentions for medical applications, especially in oncology and cancer treatment. Indeed, their capability to provide treatment and diagnosis simultaneously leads to reduce time and side effects along with improving the performance. This study aims to introduce a novel smart nano-platform composed of doxorubicin-loaded pH-responsive stealth niosomes containing CdSe/ZnS Quantum dots as an imaging agent. Drug loaded nano-platform was fabricated via thin-film hydration method and then evaluated using different physicochemical tests. The entrapment efficiency and release profile of doxorubicin were assessed at three different pH (4, 6.5, and 7.4). Biological features and imaging ability of the nanoparticles were also evaluated by MTT assay, apoptosis assay, and fluorescence microscopy. Results showed that the fabricated nanoparticles were round-shaped, with a mean size of about 100 +/- 10 nm, -2 mV surface charge, and about 87% entrapment efficiency. The drug release profile presented a pH-responsive behavior (80, 60, and 40% drug release in pH 4, 6.5, and 7.4, respectively). The bioactivity assessments showed nearly 55% cytotoxicity effects via inducing cell apoptosis. Besides, the uptake of samples by the cells was confirmed through fluorescence imaging. Based on the results, this new nanoformulation could be considered as a candidate for future cancer theranostic applications.