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  • PFK-158 br Introduction br International agency for research

    2020-08-03


    1. Introduction
    International agency for research on cancer in 2012 announced the statistics for all cancers. According to this, breast cancer has been iden-tified as the most frequent malignant disease in women worldwide with an estimated 1.67 million new cases and causes 6.4% of the total death [1]. After surgical removal of primary solid tumor, chemotherapy and radiotherapy are the next approaches for the treatment of remain-ing cancer cells [2]. Current chemotherapeutic drugs have not been sat-isfactory because of killing healthy cells and causing toxicity to the patient as indicated by the high death rate. Therefore, it is critical to dis-cover new effective and safe chemotherapeutics which could target cancerous cells specifically [3].
    Recently, with the tumor biology knowledge, many chemotherapeu-tic drugs are formulated in the form of nanoparticles which has more benefits than free drugs [4]. By exploiting the structural features of tumor environment, nanocarriers can accumulate in tumors through the enhanced permeability and retention (EPR) effect [4,5]. However, EPR-mediated passive targeting of nanoparticles suffers from difficulties in intracellular drug delivery [4]. Therefore, active targeting is more de-sirable to improve specificity and delivery efficiency to cancer cells.
    Corresponding author.
    E-mail address: [email protected] (S.A. Shojaosadati).
    Active tumor targeting is achieved by conjugating nanoparticles to mol-ecules which bind to overexpressed PFK-158 or receptors on the target tumor cells. These targeting molecules can be categorized as proteins, nucleic acids such as aptamers, or the other receptor ligands (peptides, vitamins, and carbohydrates) [4].
    In the case of breast cancer, 15%–20% of all diagnosed ones are spec-ified by the overexpression of HER2 protein [6]. HER2-positive breast cancer causes poor survival in patients due to high proliferation, inva-siveness, metastasis rates and higher recurrence compared to the other types of breast cancer [7]. In most cases, HER2-positive breast can-cers are resistance to conventional therapies such as hormonal thera-pies and chemotherapies [7,8]. Therefore, the development of novel targeted therapy approaches against HER2-positive breast cancer are crucially essential. Trastuzumab, the humanized anti-HER2 monoclonal antibody, has been approved since 1998 for treatment of metastatic HER2-positive breast cancer [9]. However, according to reports in the literature, therapeutic resistance is occurred with trastuzumab treat-ment as either single drug or in combination with other chemotherapies that it seems development of novel HER2-targeting ligands for treat-ment of HER2 overexpressing breast cancer is necessary [8].
    Liu et al. developed a novel DNA aptamer (HB5) capable of binding to HER2 protein by using systematic evolution of ligands by exponential enrichment technology (SELEX) and exploited its role as a targeting li-gand for delivering doxorubicin (Dox) to HER2-positive breast cancer cells in vitro [10]. Aptamers present promising advantages over antibod-ies, such as small size, excellent stability, better tissue penetration, high
    reproducibility, easy to synthesize, characterize and modify, low cost, and non-immunogenic [11]. Due to these characteristics, in this study, HER2-bonding aptamer has been utilized to construct a new targeted nanoparticle for anti-cancer drug delivery.
    Curcumin (CCM) is a natural polyphenol molecule extracted from turmeric (Curcuma longa) which has several proved important thera-peutic effects such as antioxidant, anti-inflammatory, anticarcinogenic, antiviral and antimicrobial, antiarthritic, and antiangiogenic [12]. Partic-ularly, curcumin has potent anticancer effect because it attacks multiple pathways, suppress proliferation of a wide variety of tumor cells, pro-motion and metastasis [13]. However, its clinical application is limited due to low water solubility and poor bioavailability. Different drug de-livery approaches which are based on nanoparticles such as liposomal curcumin [14] could improve stability and solubility of curcumin in aqueous media, so enhance its bioavailability and increase its pharma-cological activities [15–17].
    Among NPs fabricated from different polymers, human serum albu-min NPs have been considered because of some advantages such as high stability during storage and in vivo, excellent biocompatibility, biode-gradability, being non-toxic and non-antigenic [18]. Albumin has been known as a potent drug carrier in the history of pharmacology. In this context, low-molecular weight drugs could be coupled to endogenous albumin, conjugated with exogenous albumin or encapsulated into al-bumin nanoparticles [19]. Among these approaches, albumin nanopar-ticles have attracted more attention in the clinical setting due to high drug loading capacity [20]. Moreover, there are many amine and car-boxyl functional groups in the albumins' surface which can be used for surface modification results in targeting ability and unique responsibil-ity [21]. Indeed, surface modification of NPs with targeting molecules is essential for anticancer drugs which can enhance drug concentration in the targeted organs or tissues leads to decreasing the drug dosage and toxic side effects.