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Piperacillin (Pip) is a broad spectrum β-lactam against most Gram-positive and Gram-negative aerobic and anaerobic bacteria. However, bacterial resistance restricts its benefits for the treatment of infectious diseases. Recently, nanoliposomal systems have been investigated as encouraging strategies to address this issue owing to their immense potential. We aimed to encapsulate Pip in liposomal nanoparticles and study their antibacterial activities in vitro against Pseudomonas aeruginosa (P. aeruginosa). Different liposomes were prepared based on the freeze-drying of a monophase solution method. Then, they were characterized in terms of size, zeta potential, polydispersity-index, and morphology. For further analysis, spectra of ATR-FTIR and XRD were taken for liposomal Pip. Encapsulation efficiency (EE) was determined via agar diffusion assay. Also, minimum inhibitory concentrations (MICs) were investigated by the standard broth macro-dilution method. The liposomes were from 100.9 to 444.13 nm with z-potential of − 30.70 to − 10.57 mV. EE of the selected formulation was 53.1%. TEM results showed that the liposomes were nanosized and almost spherical. ATR-FTIR results confirmed the full encapsulation of Pip in nanoliposomes. The X-ray pattern indicated that the liposomal Pip was amorphous. The MIC (10.6 µg/ml) of the nanoliposomal Pip against P. aeruginosa was one-half of the MIC (21.25 µg/ml) of free Pip for the same organisms. Considering four aspects (nanosized liposomes, no need for sterilization, suitable EE and enhanced antibacterial effects), this preparation method seems promising and may be used to overcome the bacterial resistance relative to Pip.

Breast cancer (BC) is the most common type of malignancy in women. A subset of breast cancers show resistance to endocrine-based therapies. The estrogen receptor (ER) plays a critical role in developing hormone-dependent BC. Loss of ER contributes to resistance to tamoxifen therapy and may contribute to mortality. Thus, it is crucial to overcome this problem. Here, using luciferase reporter assays, qRT-PCR, and Western blot analyses, we demonstrate that the microRNA miR-486–5p targets HMGA1 mRNA, decreasing its mRNA and protein levels in ER-positive (ER+) BC cells. Consistently, miR-486–5p is significantly downregulated, whereas HMGA1 is considerably upregulated in ER+ BC samples. Remarkably, while both miR-486–5p and tamoxifen individually cause G2/M cell cycle arrest, combination treatment synergistically causes profound cell death, specifically in tamoxifen-resistant ER+ cells but not in tamoxifen-sensitive ER+ cells. Combined treatment with miR-486–5p and tamoxifen also additively reduces cell migration, invasion, colony formation, mammary spheroid formation and a CD24-CD44+ cell population, representing decreased cancer stemness. However, these phenomena are independent of the tamoxifen responsiveness of the ER+ BC cells. Thus, miR-486–5p and tamoxifen exhibit additive and synergistic tumor-suppressive effects, most importantly causing profound cell death specifically in tamoxifen-resistant BC cells. Therefore, our work suggests that combining miR-486–5p replacement therapy with tamoxifen treatment is a promising strategy to treat endocrine therapy-resistant BC. Breast cancer (BC) is the most common type of malignancy in women. A subset of breast cancers show resistance to endocrine-based therapies. The estrogen receptor (ER) plays a critical role in developing hormone-dependent BC. Loss of ER contributes to resistance to tamoxifen therapy and may contribute to mortality. Thus, it is crucial to overcome this problem. Here, using luciferase reporter assays, qRT-PCR, and Western blot analyses, we demonstrate that the microRNA miR-486–5p targets HMGA1 mRNA, decreasing its mRNA and protein levels in ER-positive (ER+) BC cells. Consistently, miR-486–5p is significantly downregulated, whereas HMGA1 is considerably upregulated in ER+ BC samples. Remarkably, while both miR-486–5p and tamoxifen individually cause G2/M cell cycle arrest, combination treatment synergistically causes profound cell death, specifically in tamoxifen-resistant ER+ cells but not in tamoxifen-sensitive ER+ cells. Combined treatment with miR-486–5p and tamoxifen also additively reduces cell migration, invasion, colony formation, mammary spheroid formation and a CD24-CD44+ cell population, representing decreased cancer stemness. However, these phenomena are independent of the tamoxifen responsiveness of the ER+ BC cells. Thus, miR-486–5p and tamoxifen exhibit additive and synergistic tumor-suppressive effects, most importantly causing profound cell death specifically in tamoxifen-resistant BC cells. Therefore, our work suggests that combining miR-486–5p replacement therapy with tamoxifen treatment is a promising strategy to treat endocrine therapy-resistant BC.

Background: Considering the complex nature of gastrointestinal cancer, different methods including surgery, radiotherapy, and chemotherapy are considered for the treatment. Novel strategies including silencing of oncogenes using safe delivery systems could be considered as a novel approach in colorectal cancer treatment. The aim of this study was to investigate the silencing effect of high mobility group A2 (HMGA2) small interfering RNA (siRNA)–loaded nanoliposomes on gastrointestinal cancers. Methods: The siRNA‐lipoplexes were prepared using dioleoyl trimethylammonium propane (DOTAP)/cholesterol (Chol)/1, 2‐dioleoyl‐sn‐glycero‐3‐phosphoethanolamine (DOPE) through the freeze‐drying of a monophase solution method. The size, polydispersity index (PDI), and zeta‐potential of nanoliposomes were determined using Zetasizer analyzer. The morphology of the nanoliposomes was determined by transmission electron microscopy (TEM). The agarose gel‐ retardation assay was carried out to confirm the loading of siRNAs into liposome. The silencing of the HMGA2 in cancer cells was evaluated by quantitative reverse‐ transcription polymerase chain reaction (qRT‐PCR). The effect of liposomes on cell cytotoxicity was studied by MTT assay. The inhibitory effect of siRNA‐loaded liposomes was evaluated by a wound‐healing assay. The apoptosis induction was investigated via the annexin V/propidium iodide assay. Results: The size, PDI, and zeta‐potential of the prepared liposomes were found to be 350 nm, 0.67, and 86.3 mV, respectively. They were spherical in shape and could efficiently associate with siRNA. The results of gene silencing showed that the optimum condition of HMGA2 silencing was 80 pmol HMGA2 and 24 hours after treatment in each cancer cell lines. MTT assays indicated that silencing of HMGA2 in optimal condition could reduce the viability of the cancer cells more than 60% in the three cell lines. The result of the apoptosis assay showed more than 50% of the cell deaths related to the apoptosis in all three cell lines. The gene expression evaluation confirmed that apoptosis was induced via the intrinsic pathway inducing both caspase‐3 and ‐9 expressions. Also, the reduction in Bcl2 J Cell Biochem. 2018;1-10. wileyonlinelibrary.com/journal/jcb © 2018 Wiley Periodicals, Inc. | 1 expression confirmed the activation apoptosis pathway in the treated cancer cells. The wound‐healing assay showed the suppression of cancer cell migration after treatment with the prepared nanoliposomes. Conclusion: The results of this study showed the HMGA2 siRNA‐loaded nanoliposomes could be effective in the treatment of gastrointestinal cancers.