Development, Optimization, and in vitro Evaluation of Silybin-loaded PLGA Nanoparticles and Decoration with 5TR1 Aptamer for Targeted Delivery to Colorectal Cancer Cells.

Chemotherapeutic agents often lack specificity, intratumoral accumulation, and face drug resistance. Targeted drug delivery systems based on nanoparticles (NPs) mitigate these issues. Poly (lactic-co-glycolic acid) (PLGA) is a well-studied polymer, commonly modified with aptamers (Apts) for cancer diagnosis and therapy. In this study, silybin (SBN), a natural agent with established anticancer properties, was encapsulated into PLGA NPs to control delivery and improve its poor solubility. The field-emission scanning electron microscopy (FE-SEM) showed spherical and uniform morphology of optimum SBN-PLGA NPs with 138.57±1.30nm diameter, 0.202±0.004 polydispersity index (PDI), -16.93±0.45mV zeta potential (ZP), and 70.19±1.63% entrapment efficiency (EE). The results of attenuated total reflectance-Fourier transform infrared (ATR-FTIR) showed no chemical interaction between formulation components, and differential scanning calorimetry (DSC) thermograms confirmed efficient SBN entrapment in the carrier. Then, the optimum formulation was functionalized with 5TR1 Apt for active targeted delivery of SBN to colorectal cancer (CRC) cells in vitro. The SBN-PLGA-5TR1 nanocomplex released SBN at a sustained and constant rate (zero-order kinetic), favoring passive delivery to acidic CRC environments. The MTT assay demonstrated the highest cytotoxicity of the SBN-PLGA-5TR1 nanocomplex in C26 and HT29 cells and no significant cytotoxicity in normal cells. Apoptosis analysis supported these results, showing early apoptosis induction with SBN-PLGA-5TR1 nanocomplex which indicated this agent could cause programmed death more than necrosis. This study presents the first targeted delivery of SBN to cancer cells using Apts. The SBN-PLGA-5TR1 nanocomplex effectively targeted and suppressed CRC cell proliferation, providing valuable insights into CRC treatment without harmful effects on healthy tissues.

Effects of Boswellia species on viral infections with particular attention to SARS-CoV-2.

The emergence of pathogenic viruses is a worldwide frequent cause of diseases and, therefore, the design of treatments for viral infections stands as a significant research topic. Despite many efforts, the production of vaccines is faced with many obstacles and the high rate of viral resistance caused a severe reduction in the efficacy of antiviral drugs. However, the attempt of developing novel natural drugs, as well as the exertion of medicinal plants, may be an applicable solution for the treatment of viral diseases. Boswellia species exhibited a wide range of pharmacological activities in various conditions such as bronchial asthma, rheumatism, and Crohn's illness. Additionally, pharmacological studies reported the observance of practical antiviral activities from different parts of this substance, especially the oleo-gum-resin. Therefore, this work provided an overview on the antiviral properties of Boswellia species and their potential therapeutic effects in the field of COVID-19 pandemic.

Application of the catalytic activity of gold nanoparticles for development of optical aptasensors.

Biosensor technology is considered to be a great alternative in analytical techniques over the conventional methods. Among many recently developed techniques and devices, aptasensors are interesting because of their high specificity, selectivity and sensitivity. Combining aptamer as a biological recognition element with gold nanoparticles (AuNPs) as probe, are becoming more general owing to their beneficial properties, including low cost and ability to analyze specific targets on-site and using naked eye. Hydrogen bonds, nucleic acid hybridization, aptamer-target and antigen-antibody binding, Raman signature, enzyme inhibition, and enzyme-mimicking activity are main different sensing strategies exploited in AuNPs-based optical aptasensors. In this review article, we discussed the recent advances in optical aptasensors with a special emphasis on the catalytic activity property of AuNPs.

A Systematic Review on the Genotoxic Effects of Selective Serotonin Reuptake Inhibitors.

Depression is a mental disorder and a major public health concern affecting millions of people worldwide. It is a common disorder that has been associated with several medical comorbidities often linked with aging, such as dementia, type II diabetes, cardiovascular and cerebrovascular diseases, as well as metabolic syndrome. There are a variety of medications available for depression treatment. Selective serotonin reuptake inhibitors (SSRIs) are one of the antidepressant drug classes that are most widely used to treat depressive disorders and depressive symptoms in other diseases. Due to many contradictory findings on the adverse effects and toxicities of SSRIs (especially genotoxicities), we reviewed the genotoxic effects of these drugs. Based on the guidelines proposed in the PRISMA statement, we performed a systematic review by searching international electronic databases including PubMed, Scopus, Embase, and Web of Science to find the published documents on SSRIs and their genotoxic effects from January 1990 to November 2019. After the removal of 203 duplicate articles, 385 articles were screened and 167 articles met the inclusion criteria and qualified for evaluation of their full texts. After this, 26 articles were appropriate for final review. This revealed that the proportion of genotoxicities was highest for citalopram and fluoxetine, with a smaller proportion for sertraline. Limited documentations showed genotoxic and partial genotoxic effects for paroxetine and escitalopram, respectively. Although a number of studies have found genotoxic effects of SSRIs, there are also some factors including doses, duration of exposure, model of experiments, and the type of technique assay that may affect the results.

Aptamer-conjugated PLGA nanoparticles for delivery and imaging of cancer therapeutic drugs.

Most problems associated with chemotherapeutic agents involve non-specific cytotoxicity, low intratumoral accumulation and drug resistance. Targeted drug delivery systems (TDDS) based on nanoparticles (NPs) are a new strategy for better therapeutic efficiency, along with reduction of side effects commonly seen with cancer drugs. Poly (lactic-co-glycolic acid) (PLGA), as one of the furthest developed synthetic polymer, has gained significant attention because of excellent properties-including biodegradability and biocompatibility, controlled release of drug, protection of drug or gene from decomposition and ability to modify surface with targeting agents for both cancer diagnosis and therapy. Aptamers are single-stranded RNA or DNA that can fold through intramolecular interactions into specific three-dimensional structures to selectively and exclusively bind with interested biomarkers. In this review, we explain the latest developments regarding the application of aptamer-decorated PLGA NPs in delivery of therapeutic agents or cancer-related genes into cancer cells. Additionally, we discuss the most recent efforts in the field of aptamer-grafted PLGA-based NPs as theranostics and stimuli-responsive agents.

Formulation and evaluation of anticancer and antiangiogenesis efficiency of PLA-PEG nanoparticles loaded with galbanic acid in C26 colon carcinoma, in vitro and in vivo.

Galbanic acid (GBA) is an active sesquiterpene coumarin derivative, with various medicinal benefits, including anticancer properties. However, the low solubility of GBA is the main limitation of its clinical applications. In this study, we used a nanosystem based on poly (D, l-lactide)-polyethylene glycol (PLA-PEG), for the delivery of GBA to C26 colon carcinoma cells. The physicochemical characteristics of nanoparticles (NPs) prepared by the emulsification-evaporation method were evaluated. MTT assay was used to compare the anticell proliferation of GBA and PLA-PEG-GBA against C26 cell lines. PLA-PEG-NPs with an average size of about 140 nm had an enhanced release of GBA at a pH of 5.5 compared with a pH of 7.4. Cytotoxicity studies showed that the IC 50 of the PLA-PEG-GBA NPs (8 µM) was significantly lower than free GBA (15 µM). In the in vivo study, PLA-PEG-GBA NPs exhibited remarkable efficacy and reduced in vivo toxicity in C26 colon carcinoma tumor-bearing female BALB/c mice. To study the antiangiogenesis effect of the NPs, tumor sections were stained with an anti CD34 antibody. The results show the CD34 (+) vessels were decreased in the GBA and PLA-PEG-GBA treated mice by more than 75% and 90%, respectively. These results suggest that the encapsulation of GBA into the PLA-PEG could potentially be used for the treatment of colorectal cancer.

Smart aptamer-modified calcium carbonate nanoparticles for controlled release and targeted delivery of epirubicin and melittin into cancer cells in vitro and in vivo.

To explore the effect of combination therapy of epirubicin (Epi) and melittin (Mel) to cancer cells, calcium carbonate nanoparticles (CCN), as carriers, were developed which were modified with MUC1-Dimer aptamers as targeting agents. Both Epi and Mel were delivered at the same time to cancer cells overexpressing the target of MUC1 aptamer, mucin 1 glycoproteins (MCF7 and C26 cells). CCN were prepared with a water-in-oil emulsion method. Epi and Mel were separately encapsulated in CCN and the nanoparticles were modified with MUC1-Dimer aptamers. In vitro studies, including MTT assay, flow cytometry analysis and fluorescence imaging were applied to investigate the targeting and cell proliferation inhibition capabilities of MUC1-Dimer aptamer-CCN-Mel complex and MUC1-Dimer aptamer-CCN-Epi complex in the target (MCF-7 and C26 cells) and nontarget (HepG2) cells. Also, the function of the developed complexes was analyzed using in vivo tumor growth inhibition. The release of Epi from MUC1-Dimer aptamer-CCN-Epi complex was pH-sensitive. Cellular uptake studies showed more internalization of the MUC1-Dimer aptamer-CCN-Epi complex into MCF-7 and C26 cells (target) compared to HepG2 cells (nontarget). Interestingly, the MUC1-Dimer aptamer-CCN-Mel complex and MUC1-Dimer aptamer-CCN-Epi complex indicated very low toxicity as compared to target cells. Moreover, co-delivery of Epi and Mel using the mixture of MUC1-Dimer aptamer-CCN-Mel complex and MUC1-Dimer aptamer-CCN-Epi complex exhibited strong synergistic cytotoxicity in MCF-7 and C26 cells. Furthermore, the presented complexes had a better function to control tumor growth in vivo compared to free Epi.

A Novel AS1411 Aptamer-Based Three-Way Junction Pocket DNA Nanostructure Loaded with Doxorubicin for Targeting Cancer Cells in Vitro and in Vivo.

Active targeting of nanostructures containing chemotherapeutic agents can improve cancer treatment. Here, a three-way junction pocket DNA nanostructure was developed for efficient doxorubicin (Dox) delivery into cancer cells. The three-way junction pocket DNA nanostructure is composed of three strands of AS1411 aptamer as both a therapeutic aptamer and nucleolin target, the potential biomarker of prostate (PC-3 cells) and breast (4T1 cells) cancers. The properties of the Dox-loaded three-way junction pocket DNA nanostructure were characterized and verified to have several advantages, including high serum stability and a pH-responsive property. Cellular uptake studies showed that the Dox-loaded DNA nanostructure was preferably internalized into target cancer cells (PC-3 and 4T1 cells). MTT cell viability assay demonstrated that the Dox-loaded DNA nanostructure had significantly higher cytotoxicity for PC-3 and 4T1 cells compared to that of nontarget cells (CHO cells, Chinese hamster ovary cell). The in vivo antitumor effect showed that the Dox-loaded DNA nanostructure was more effective in prohibition of the tumor growth compared to free Dox. These findings showed that the Dox-loaded three-way junction pocket DNA nanostructure could significantly reduce the cytotoxic effects of Dox against nontarget cells.

An aptamer-based colorimetric lead(II) assay based on the use of gold nanoparticles modified with dsDNA and exonuclease I.

The authors describe a colorimetric method for the sensitive and selective detection of Pb(II). It is based on the use exonuclease I (Exo I), a Pb(II)-binding aptamer bound to gold nanoparticles (AuNPs), and a DNA strand that complementary to the aptamer. In the absence of Pb(II), the dsDNA on the AuNPs prevents aggregation of the AuNPs in the presence of NaCl. In the presence of Pb(II), however, the aptamer binds Pb(II) and complementary strand is released and digested by Exo I. As a result, the solution of AuNPs undergoes a color change from red to purple if salt is added to the sample. The assay is selective for Pb(II) and has a limit of detection as low as 2.4 nM. It was successfully applied to the determination of Pb(II) in spiked tap water. Graphical abstract Schematic presentation of the aptamer based method for Pb2+ detection via salt-induced aggregation of gold nanoparticles and colorimetric quantitation.

Fluorometric aptasensing of the neonicotinoid insecticide acetamiprid by using multiple complementary strands and gold nanoparticles.

A fluorometric aptamer-based assay was developed for ultrasensitive and selective determination of the neonicotinoid insecticide acetamiprid. The method is based on the use of an aptamer against acetamiprid, multiple complementary strands (CSs), and gold nanoparticles (AuNPs). It is found that by using different CSs, the sensitivity and selectivity of the method is enhanced. On addition of acetamiprid to the aptamer, they will bind to each other and CS1-fluorescein (FAM)-labeled CS2 (as a dsDNA) will be formed. The FAM-labeled dsDNA does not bind to the AuNPs (as a strong quencher) and remains free in the environment, resulting in a strong fluorescence intensity. Without the introduction of acetamiprid, FAM-labeled CS2 binds to AuNPs directly and indirectly through hybridization with CS3 immobilized on the surface of the AuNPs. So, the fluorescence intensity of FAM-labeled CS2 is significantly quenched by AuNPs. The method can detect acetamiprid in the 5 to 50 nM concentration range with a 2.8 nM detection limit. The assay was applied to the determination of acetamiprid in spiked tap water where is gave recoveries that ranged between 95.4% and 94.4%. Graphical abstract (a) In the presence of acetamiprid, aptamer interacts with acetamiprid. The formation of aptamer/acetamiprid causes pairing of complementary strand 1 with FAM-labeled complementary strand, leading to a strong fluorescence intensity. (b) In the absence of acetamiprid, aptamer is hybridized with complementary strand 1. Thus, a very weak fluorescence signal is detected.

Aptasensors for quantitative detection of Salmonella Typhimurium.

Salmonella is one of the most frequent causes of food borne infectious disease. Among nearly 2500 documented serotypes are reported, Salmonella Typhimurium is the number one serotype associated with salmonellosis worldwide. Many different methods have been developed for the detection and quantification of S. typhimurium. Most of these assays are usually expensive, time consuming and require difficult sample preparation steps. Therefore, it is necessary to develop rapid, robust, cost-effective and sensitive alternative detection methods. In the last years, aptasensors, used for detection of S. typhimurium in different samples. In this review, recent advances and applications of aptasensors for the detection and quantification of S. typhimurium in details have been summarized.

A novel chemotherapy drug-free delivery system composed of three therapeutic aptamers for the treatment of prostate and breast cancers in vitro and in vivo.

In this study, a novel chemotherapy drug-free DNA nanocomplex composed of three therapeutic aptamers (IDA, AS1411 and apMNK2F) was designed for treatment of cancer cells. For MTT assay, PC-3 and 4T1 cells (target cells) and CHO cells (nontarget cells) were treated with apMNK2F-AS1411-IDA complex (DNA nanocomplex), as well as AS1411, IDA and apMNK2F alone. Internalization of apMNK2F-AS1411-IDA complex was analyzed by fluorescence imaging and flow cytometry analysis. In the last step, the presented DNA nanocomplex was applied for prohibition of tumor growth in vivo. The results of internalization assay verified that the developed apMNK2F-AS1411-IDA complex was remarkably internalized into PC-3 and 4T1 cells, but not into CHO cells. The results of internalization assay was confirmed by MTT assay. apMNK2F-AS1411-IDA complex was more cytotoxic in PC-3 and 4T1 cells (target) and less cytotoxic in CHO cells (nontarget). Also, the DNA nanocomplex could effectively suppress the growth of tumors in vivo.

Selection of DNA aptamers against Mycobacterium tuberculosis Ag85A, and its application in a graphene oxide-based fluorometric assay.

The Mycobacterium Ag85 complex is the major secretory protein of M. tuberculosis. It is a potential marker for early diagnosis of tuberculosis (TB). The authors have identified specific aptamers for Ag85A (FbpA) via protein SELEX using magnetic beads. After twelve rounds of selection, two aptamers (Apt8 and Apt22) were chosen from different groups, and their binding constants were determined by flow cytometry. Apt22 (labeled with Atto 647N) binds to FbpA with high affinity (Kd = 63 nM) and specificity. A rapid, sensitive, and low-cost fluorescent assay was designed based on the use of Apt22 and graphene oxide, with a limit of detection of 1.5 nM and an analytical range from 5 to 200 nM of FbpA. Graphical abstract Schematic illustration of graphene oxide-based aptasensor for fluorometric determination of FbpA.

Targeted Delivery of Epirubicin to Cancer Cells by Polyvalent Aptamer System in vitro and in vivo.

PURPOSE: The clinical use of Epirubicin (Epi), as an anthracycline drug, is limited because of its cardiotoxicity. Here, an Epirubicin (Epi)-modified polyvalent aptamer system (MPAS) conjugate was developed for the treatment of both murine colon carcinoma cells (C26) and breast cancer cells (MCF-7). METHODS: Epi-MPAS conjugate formation was evaluated by fluorometric analysis. Release profiles of Epi from the developed conjugate were analyzed at pHs 5.4 and 7.4. For MTT assay (cytotoxic study) C26 and MCF-7 (target cells) and CHO cells (Chinese hamster ovary cell, nontarget) were treated with Epi, MPAS and Epi-MPAS conjugate. Internalization was assessed by fluorescence imaging and flow cytometry analysis. The designed conjugate was used for prohibition of tumor growth in vivo. RESULTS: Release of Epi from the Epi-MPAS conjugated was pH-dependent (more release at pH 5.5). Flow cytometry analysis and MTT assay showed that Epi-MPAS conjugate could significantly enhance the cellular uptake of Epi and increase its cytotoxicity in target cells as compared with non-targeted cell (CHO). Additionally, this complex could efficiently prohibit the tumor growth in vivo. CONCLUSION: In conclusion, the developed drug delivery system had the characteristics of efficient Epi loading, pH-dependent drug release and tumor targeting in vitro and in vivo.

Vitamin K (Menadione)-incorporated chitosan/alginate hydrogel as a novel product for periorbital hyperpigmentation.

The possibility of controlling periorbital hyperpigmentation disorders is one of the most important research goals in cosmetic preparations. In the current investigation, 1% vitamin K (Vit K) was incorporated into a Chitosan/alginate hydrogel which aimed to increase the dermal delivery and anti-pigmentation effect. The Vit K-hydrogel was evaluated using several different tests, including volume expansion/contraction analysis, differential scanning calorimetry (DSC), scanning electron microscopy (SEM), ultraviolet (UV) absorbance spectroscopy, and attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy. Vit K hydrogel's drug release profile showed a steady increase over time. Furthermore, the modified Vit K hydrogel formulations showed no harmful effects in an in vitro cytotoxicity study. The Vit K hydrogel was tested for dermal irritation on Wistar rats, and the hydrogel was found to be non-irritating. Furthermore, Vit K-hydrogel inhibited melanin formation (31.76 ± 1.14%) and was remarkably higher than free Vit K. In addition, Vit K-hydrogel inhibited L-dopa auto-oxidation to a greater extent (94.80 ± 2.41%) in comparison with Vit K solution (73.95 ± 1.62%). Vit K-hydrogel enhanced percutaneous transport of Vit K, according to in vitro percutaneous absorption findings, suggesting that this innovative formulation may provide new therapeutic options for periorbital hyperpigmentation.

Efficient Neural Differentiation of Mouse Embryonic Stem Cells by Mastic Gum.

Purpose: Promoting neurogenesis is a promising strategy to treat neurodegenerative disorders. In the present study, we aimed to evaluate the effect of mastic gum resin from the Pistacia lentiscus var. Chia (Anacardiaceae family) in proliferation capacity and differentiation of embryonic mesenchymal stem cells into a neural lineage. Methods: For this purpose, mastic gum was applied as a neural inducer for stem cell differentiation into the neuronal lineage. Following treatment of embryonic stem cells (ESCs) with mastic gum, verification differentiation of the ESCs into the neuronal lineage, gene expression analysis, and immunocytochemistry staining approach were performed. Results: Gene expression analysis demonstrated that mastic gum increased the expression level of neuron markers in the ESCs-derived neuron-like cells. Moreover, our immunocytochemistry staining results of two important neural stem cell markers, including Nestin and microtubule-associated protein-2 (Map2) expression confirmed that mastic gum has the potential to promote neuronal differentiation in ESCs. Conclusion: In summary, the use of mastic gum to stimulate the differentiation of ESCs into a neural lineage can be considered as a good candidate in stem cell therapy.

Recent advances in novel miRNA mediated approaches for targeting breast cancer.

Breast cancer (BC) is considered one of the most frequent cancers among woman worldwide. While conventional therapy has been successful in treating many cases of breast cancer, drug resistance, heterogenicity, tumour features and recurrence, invasion, metastasis and the presence of breast cancer stem cells can hinder the effect of treatments, and can reduce the quality of life of patients. MicroRNAs (miRNAs) are short non-coding RNA molecules that play a crucial role in the development and progression of breast cancer. Several studies have reported that aberrant expression of specific miRNAs is associated with the pathogenesis of breast cancer. However, miRNAs are emerging as potential biomarkers and therapeutic targets for breast cancer. Understanding their role in breast cancer biology could help develop more effective treatments for this disease. The present study discusses the biogenesis and function of miRNAs, as well as miRNA therapy approaches for targeting and treating breast cancer cells.

Aptamer-functionalized mesenchymal stem cells-derived exosomes for targeted delivery of SN38 to colon cancer cells.

Objectives: Known as natural nanovesicles, exosomes have attracted increased attention as biocompatible carriers throughout recent years, which can provide appropriate sources for incorporating and transferring drugs to desired cells in order to improve their effectiveness and safety. Materials and Methods: This study implicates the isolation of mesenchymal stem cells from adipocyte tissue (ADSCs) to acquire a proper amount of exosomes for drug delivery. As the exosomes were separated by ultracentrifugation, SN38 was entrapped into ADSCs-derived exosomes through the combination method of incubation, freeze-thaw, and surfactant treatment (SN38/Exo). Then, SN38/Exo was conjugated with anti-MUC1 aptamer (SN38/Exo-Apt), and its targeting ability and cytotoxicity towards cancer cells were investigated. Results: Encapsulation efficiency of SN38 into exosomes (58%) was significantly increased using our novel combination method. Furthermore, the in vitro results were indicative of the great cellular uptake of SN38/Exo-Apt and its significant cytotoxicity on Mucin 1 overexpressing cells (C26 cancer cells) without noticeable cytotoxicity on normal cells (CHO cells). Conclusion: The results propose that our approach developed an efficient method for loading SN38 as a hydrophobic drug into exosomes and decorating them with MUC1 aptamer against Mucin 1 overexpressing cells. So, SN38/Exo-Apt could be considered a great platform in the future for the therapy of colorectal cancer.

New insight into the structural changes of apoferritin pores in the process of doxorubicin loading at an acidic pH: Molecular dynamics simulations.

Apoferritin (APO-Fr) is one of the most investigated proteins proposed as an advanced structure for drug delivery systems. Herein, molecular dynamics simulation was employed to compare the opening of 3-fold and 4-fold pores in APO-Fr during the partial disassembly process at an acidic pH. We showed that more hydrophilic residues in the surface of 3-fold pores compared to 4-fold pores facilitate increased flexibility and a higher tendency to open. In particular, dissociation is induced by the presence of Doxorubicin (DOX) close to 3-fold pores. Our simulations showed loaded DOXs on the APO-Fr surface were mainly involved in the hydrogen bond interactions with the hydrophilic residues, suggesting the difficulty of hydrophobic drugs loading in APO-Fr with the partial disassembly process. However, π-π interactions as well as hydrogen bonds between protein and DOXs were mediated by the basic and acidic amino acids such as HIP128, GLU17, and LYS143 at the open pores, providing penetration of DOXs into the H-Apo-Fr. We conclude that increased drug encapsulations and loading capacity of hydrophobic drugs into the cavity of APO-Fr are feasible by further disassembly of openings to access the internal hydrophobic portions of the protein.

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.