Superparamagnetic iron oxide nanoparticles (SPIONs) have been employed in several biomedical applications where they facilitate both diagnostic and therapeutic aims. Although the potential benefits of SPIONs with different surface chemistry and conjugated targeting ligands/proteins are considerable, complicated interactions between these nanoparticles (NPs) and cells leading to toxic impacts could limit their clinical applications. Hence, elevation of our knowledge regarding the SPION-related toxicity is necessary. Here, the present review article will consider current studies and compare the potential toxic effect of SPIONs with or without identical surface chemistries on different cell lines. It centers on cellular and molecular mechanisms underlying toxicity of SPIONs. Likewise, emphasis is being dedicated for toxicity of SPIONs in various cell lines, in vitro and animal models, in vivo.

Docetaxel (DtX) was loaded in nanoliposomes based on a new remote loading method using mannitol and acetic acid as hydration buffer. DTX loading conditions were optimized, and the final formulations were prepared according to the best parameters which were HSPC/mPEG2000-DSPE/Chol (F1), HSPC/mPEG2000-DSPE/DPPG/Chol (F2), HSPC/mPEG2000-DSPE/DSPG/Chol (F3), at molar ratios of 85/5/10, 80/5/5/10, 80/5/5/10, respectively. DTX-liposomes were found of desired size (~115 nm) and homogeneity (pDi ≤ 0.2), high drug encapsulation efficacy (34-67%) and DTX concentration, and favorable stability. Passive loaded counterparts liposomes showed three times lower encapsulation efficacy compared to the remote loaded liposomes. The drug release of remote loaded liposomes in plasma 50% was significantly more controlled and less in comparison with their passive loaded counterparts (p < 0.0001). The IC50 values of formulations were determined on MCF-7, 4T1, TUBO, NIH/3T3 cell lines. The biodistribution of iodinated docetaxel as free or liposomal form exhibited significantly greater accumulation of DTX-liposomes in tumors than that of free docetaxel due to the EPR effect. In vivo experiment with BALB/c mice bearing 4T1 or TUBO breast carcinoma tumors also showed that DTX-liposomes could significantly delay tumor growth and prolonged the survival time in comparison with control and Taxotere groups at the similar dose of 8 mg/kg. F1 and F2 formulations were stable and showed good anti-tumor activity and merit further investigation. Taxanes have extremely low solubility in water and pharmaceutical concerns caused by their bulky polycyclic structure 1,2. Nanocarriers, including liposomes, micelles, and polymeric or inorganic nanoparticles have been developed to prepare a higher therapeutic efficacy, lower toxicity, and controlled delivery of chemotherapeutic agents 1,3-8. Among them, liposomes, composed of phospholipids, have been explored for their use in clinically approved formulations for more than five decades 6,9-15. Liposomes, compared with other nanocarriers, present specific advantages and promising capabilities in delivering a plethora of otherwise inefficient drugs by modifying their physicochemical characteristics and biodistribution, and by reducing the toxic effects of drugs 6,16,17. Moreover, chemical and biological stability under different storage conditions of agents and during blood circulation, and biocompatible characteristics recommend them as carriers for therapeutic agents 6,9,17,18. There are currently two liposomal formulations of docetaxel (DTX) in clinical development. LE-DT (NeoPharm, Inc.) and ATI-1123 (Azaya Therapeutics, Inc.) have undergone phase I studies and appears to be well tolerated (ClinicalTrials.gov in May 2019). In general, drug loading into the liposomes is attained by either passive or active (remote) methods 19. In passive loading method, dried thin film is hydrated in aqueous solutions containing the drug of interest. In contrast, remote loading technique is loading of a drug into performed lip...

Tumor-associated macrophages (TAMs) are an important component of the leukocytic infiltrate of the tumor microenvironment. There is persuasive preclinical and clinical evidence that TAMs induce cancer inanition and malignant progression of primary tumors toward a metastatic state through a highly conserved and fundamental process known as epithelial-mesenchymal transition (EMT). Tumor cells undergoing EMT are distinguished by increased motility and invasiveness, which enable them to spread to distant sites and form metastases. In addition, besides becoming resistant to apoptosis and antitumor drugs, they also contribute to immunosuppression and get a cancer stem-cell like phenotype. Here, we will focus on selected molecular pathways underlying EMT-in particular, the role of TAMs in the induction and maintenance of EMT-and further discuss how the targeting of TAMs through the application of nanotechnology tools allows the development of a whole new range of therapeutics.

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