Smart delivery of epirubicin to cancer cells using aptamer-modified ferritin nanoparticles.

Epirubicin (Epi) is a chemotherapy agent which is commonly used in treatment of cancers. However, despite being efficient, the tendency to use this drug is declining mostly due to its myocardiopathy and drug-resistance of tumour cells. Such side effects could be prevented using targeted nanocarriers. This study aims to evaluate targeted delivery of Epi to colon cancer cells using ferritin nanoparticles (Ft NPs) and mucin 1 (MUC1) aptamer (Apt) and formation of Apt-Epi Ft NPs. In the current study, Apt-Epi Ft NPs were prepared. Then, physicochemical properties of nanoparticles, including size and zeta potential, morphology, drug loading, drug release from nanoparticles, drug uptake of cancer cells, cytotoxicity and in vivo results were collected. The results showed that the nanoparticles were synthesised with a mean size of 37.9 nm and encapsulation efficiency of 67%. The drug release from these nanoparticles was about 90% within 4 h in acidic medium. Also, targeted delivery of Epi enhanced its anticancer effects in both in vitro and in vivo. In this study, targeted delivery of Epi using Apt-modified Ft NPs improved in vitro and in vivo results which indicates that it could be useful as a successful drug delivery system against cancer cells.

Flavonoids, the compounds with anti-inflammatory and immunomodulatory properties, as promising tools in multiple sclerosis (MS) therapy: A systematic review of preclinical evidence.

Multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), an animal model of MS, are diseases resulting in neurological disabilities that are regarded as chronic, inflammatory, and autoimmune diseases of central nervous system (CNS). In this respect, the use of anti-inflammatory compounds including flavonoids, polyphenolic compounds abundantly found in vegetables and fruits, has proposed to combat MS to dampen the inflammation and thereby ameliorating the disease severity. The objective of this study was to clarify the probable therapeutic effect of flavonoids for treatment of MS. Therefore, only English published articles that reported the therapeutic effect of flavonoids alone or in combination with other anti-MS therapeutic agents on MS, were selected by searching scientific electronic databases including PubMed, Scopus and Web of Science. Evaluation of the selected researches (686) showed that a total of 13 studies were suitable to be included in this systematic review. Interestingly, all of the studies (11 studies concerning EAE and 2 studies concerning MS) reported positive outcomes for the therapeutic effect of flavonoids on EAE and MS. All flavonoid compounds which are mentioned herein could successfully decrease the maximum clinical score of EAE, which is particularly connected to the anti-inflammatory property of these compounds. The literature review clearly discloses that flavonoids alone or in combination with other anti-MS therapeutic agents can pave the way for improving MS therapeutic strategies.

Therapeutic applications of AS1411 aptamer, an update review.

Nucleolin or C23, is one of the most abundant non-ribosomal phosphoproteins of nucleolus. However, in several cancers, nucleolin is highly expressed both intracellularly and on the cell surface. So, it is considered as a potential target for the diagnosis and cancer therapy. Targeting nucleolin by compounds such as AS1411 aptamer can reduce tumor cell growth. In this regard, interest has increased in nucleolin as a molecular target for overcoming cancer therapy challenges. This review paper addressed recent progresses in nucleolin targeting by the G-rich AS1411 aptamer in the field of cancer therapy mainly over the past three years.

In vitro selection of CD70 binding aptamer and its application in a biosensor design for sensitive detection of SKOV-3 ovarian cells.

Single-stranded DNA aptamers recognizing CD70 molecule overexpressed in some tumor cell lines was isolated by means of systematic evolution of ligands by exponential enrichment (SELEX). Both purified CD70 protein and CD70-expressing cells were used to isolate target-specific aptamer. After certain rounds of protein-based SELEX and cell-SELEX (ten and seven rounds, respectively), Aptamer 928 (hereafter Apt928) with high affinity and specificity for CD70 was obtained. The specific binding of the aptamer to its target could block interaction of CD70 with CD27 (known as CD70 receptor). Dissociation constant of Apt928 was calculated to be 66 nmol L-1. Moreover, ATTO 674N-labeled Apt928 was applied as a fluorescent aptasensor for rapid and sensitive detection of SKOV-3 cells as CD70-positive cells. The detection limit of this aptasensor was 14 cells mL-1.

SELEX methods on the road to protein targeting with nucleic acid aptamers.

Systematic evolution of ligand by exponential enrichment (SELEX) is an efficient method used to isolate high-affinity single stranded oligonucleotides from a large random sequence pool. These SELEX-derived oligonucleotides named aptamer, can be selected against a broad spectrum of target molecules including proteins, cells, microorganisms and chemical compounds. Like antibodies, aptamers have a great potential in interacting with and binding to their targets through structural recognition and are therefore called "chemical antibodies". However, aptamers offer advantages over antibodies including smaller size, better tissue penetration, higher thermal stability, lower immunogenicity, easier production, lower cost of synthesis and facilitated conjugation or modification with different functional moieties. Thus, aptamers represent an attractive substitution for protein antibodies in the fields of biomarker discovery, diagnosis, imaging and targeted therapy. Enormous interest in aptamer technology triggered the development of SELEX that has underwent numerous modifications since its introduction in 1990. This review will discuss the recent advances in SELEX methods and their advantages and limitations. Aptamer applications are also briefly outlined in this review.

Cell growth inhibition and apoptotic effects of a specific anti-RTFscFv antibody on prostate cancer, but not glioblastoma, cells.

Background: Single chain antibody (scFv) has shown interesting results in cancer immunotargeting approaches, due to its advantages over monoclonal antibodies. Regeneration and tolerance factor (RTF) is one of the most important regulators of extracellular and intracellular pH in eukaryotic cells. In this study, the inhibitory effects of a specific anti-RTF scFv were investigated and compared between three types of prostate cancer and two types of glioblastoma cells.  Methods: A phage antibody display library of scFv was used to select specific scFvs against RTF using panning process. The reactivity of a selected scFv was assessed by phage ELISA. The anti-proliferative and apoptotic effects of the antibody on prostate cancer (PC-3, Du-145 and LNCaP) and glioblastoma (U-87 MG and A-172) cell lines were investigated by MTT and Annexin V/PI assays.  Results: A specific scFv with frequency 35% was selected against RTF epitope. This significantly inhibited the proliferation of the prostate cells after 24 h. The percentages of cell viability (using 1000 scFv/cell) were 52, 61 and 73% for PC-3, Du-145 and LNCaP cells, respectively, compared to untreated cells. The antibody (1000 scFv/cell) induced apoptosis at 50, 40 and 25% in PC-3, Du-145 and LNCaP cells, respectively. No growth inhibition and apoptotic induction was detected for U-87 and A172 glioblastoma cells.  Conclusions: Anti-RTFscFv significantly reduced the proliferation of the prostate cancer cells. The inhibition of cell growth and apoptotic induction effects in PC-3 cells were greater than Du-145 and LNCaP cells. This might be due to higher expression of RTF antigen in PC-3 cells and/or better accessibility of RTF to scFv antibody. The resistance of glioblastoma cells to anti-RTF scFv offers the existence of mechanism(s) that abrogate the inhibitory effect(s) of the antibody to RTF. The results suggest that the selected anti-RTF scFv antibody could be an effective new alternative for prostate cancer immunotherapy.